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1.
Ann Surg Oncol ; 2024 Jul 13.
Article in English | MEDLINE | ID: mdl-39003380

ABSTRACT

BACKGROUND: The prognostic impact of genetic mutations for patients who undergo cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) of colorectal origin (CRC) is not well defined. OBJECTIVE: We aimed to describe the genetic classifications in an unsupervised fashion, and the outcomes of this patient population. METHODS: A retrospective, bi-institutional study was performed on patients who underwent CRS-HIPEC with targeted mutation data with a median follow-up time of 61 months. Functional link analysis was performed using STRING v11.5. Genes with similar functional significance were clustered using unsupervised k-means clustering. Chi-square, Kaplan-Meier, and the log-rank test were used for comparative statistics. RESULTS: Sixty-four patients with peritoneal carcinomatosis from CRC origin underwent CRS-HIPEC between 2007 and 2022 and genetic mutation data were extracted. We identified 19 unique altered genes, with KRAS (56%), TP53 (33%), and APC (22%) being the most commonly altered; 12.5% had co-altered KRAS/TP53. After creating an interactome map, k-means clustering revealed three functional clusters. Reactome Pathway analysis on three clusters showed unique pathways (1): Ras/FGFR3 signaling; (2) p53 signaling; and (3): NOTCH signaling. Seventy-one percent of patients in cluster 1 had KRAS mutations and a median overall survival of 52.3 months (p < 0.05). CONCLUSIONS: Patients with peritoneal carcinomatosis (PC) of CRC origin who underwent CRS-HIPEC and with tumors that harbored mutations in cluster 1 (Ras/FGFR3 signaling) had worse outcomes. Pathway disruption and a cluster-centric perspective may affect prognosis more than individual genetic alterations in patients with PC of CRC origin.

2.
J Clin Exp Hepatol ; 14(6): 101408, 2024.
Article in English | MEDLINE | ID: mdl-38975608

ABSTRACT

Acute liver failure (ALF) typically presents with encephalopathy and impairment in the synthetic function of the liver. Weight loss supplements have been associated with ALF, and their use has only been increasing in the United States. We report a case of a 42-year-old woman with a history of Gilbert's syndrome who presented to the hospital with ALF secondary to weight loss supplements, who ultimately required liver transplantation. This is the first known case of conjugated linoleic acid (CLA) toxicity requiring liver transplantation in the United States.

3.
J Surg Orthop Adv ; 33(2): 80-83, 2024.
Article in English | MEDLINE | ID: mdl-38995062

ABSTRACT

The purpose of this study was to compare two sources of nerve graft for brachial plexus reconstruction: the denervated superficial branch of the radial nerve (SBRN) and the sural nerve. Ninety-seven patients who underwent brachial plexus reconstruction with denervated SBRN nerve (24 patients with 24 grafts) or with sural nerve grafting (73 patients with 83 nerve grafts) were included. The two groups were compared with respect to postoperative muscle reinnervation, disabilities of the arm, shoulder, and hand (DASH) scores. In the SBRN group, only four (17%) of the nerve grafts provided grade III or higher muscle function. In the sural nerve group, 31 (37%) of the nerve grafts provided grade III or higher muscle function. Smoking had a negative impact on muscle recovery. Denervated SBRN grafts are associated with inferior outcomes when compared with sural nerve grafts in the treatment of traumatic adult brachial plexus injuries. (Journal of Surgical Orthopaedic Advances 33(2):080-083, 2024).


Subject(s)
Brachial Plexus , Radial Nerve , Sural Nerve , Humans , Sural Nerve/transplantation , Adult , Male , Female , Brachial Plexus/injuries , Brachial Plexus/surgery , Radial Nerve/injuries , Radial Nerve/surgery , Middle Aged , Retrospective Studies , Young Adult , Nerve Transfer/methods , Recovery of Function
4.
Article in English | MEDLINE | ID: mdl-38995200

ABSTRACT

Restoration of elbow flexion is a priority in treating adult traumatic brachial plexus injuries. A tendon transfer is an ideal option for patients not candidates for reconstructive nerve surgery or free-functioning muscle transfer. For patients with a partial brachial plexus injury or a pan plexus injury with adequate recovered triceps function and loss of elbow flexion, a triceps-to-biceps tendon transfer is a nonmicrosurgical option to restore elbow flexion. The technique of triceps-to-biceps transfer in which the complete triceps tendon is transferred laterally, secured lateral to the radial tuberosity, and reinforced with suture to the biceps tendon is described.

5.
Article in English | MEDLINE | ID: mdl-38907610

ABSTRACT

Serial physical examination is often required in the evaluation of brachial plexus injuries. (Noland, 2019) A comprehensive evaluation that includes a thorough history, electrodiagnostic evaluation, and imaging studies, in addition to physical examination, can provide valuable information about the location of the lesion, prognosis for recovery, and whether surgical intervention is necessary. After brachial plexus reconstruction, physical examinations are also performed to document clinical improvement and identify any residual issues. The videos included in this clinical examination techniques section demonstrate the muscle strength examination testing for the brachial plexus and offer best practices for documentation.

6.
Viruses ; 16(6)2024 May 22.
Article in English | MEDLINE | ID: mdl-38932113

ABSTRACT

Tick-borne flaviviruses (TBFV) can cause severe neuroinvasive disease which may result in death or long-term neurological deficit in over 50% of survivors. Multiple mechanisms for invasion of the central nervous system (CNS) by flaviviruses have been proposed including axonal transport, transcytosis, endothelial infection, and Trojan horse routes. Flaviviruses may utilize different or multiple mechanisms of neuroinvasion depending on the specific virus, infection site, and host variability. In this work we have shown that the infection of BALB/cJ mice with either Powassan virus lineage I (Powassan virus) or lineage II (deer tick virus) results in distinct spatial tropism of infection in the CNS which correlates with unique clinical presentations for each lineage. Comparative transcriptomics of infected brains demonstrates the activation of different immune pathways and downstream host responses. Ultimately, the comparative pathology and transcriptomics are congruent with different clinical signs in a murine model. These results suggest that the different disease presentations occur in clinical cases due to the inherent differences in the two lineages of Powassan virus.


Subject(s)
Brain , Encephalitis Viruses, Tick-Borne , Encephalitis, Tick-Borne , Mice, Inbred BALB C , Animals , Mice , Encephalitis Viruses, Tick-Borne/pathogenicity , Encephalitis Viruses, Tick-Borne/physiology , Encephalitis Viruses, Tick-Borne/genetics , Encephalitis, Tick-Borne/virology , Encephalitis, Tick-Borne/pathology , Brain/virology , Brain/pathology , Inflammation/virology , Disease Models, Animal , Female , Transcriptome
7.
J Intensive Care Med ; : 8850666241257417, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38794858

ABSTRACT

BACKGROUND: Arterial catheter placement for hemodynamic monitoring is commonly performed in critically ill patients. The radial and femoral arteries are the two sites most frequently used; there is limited data on the use of the axillary artery for this purpose. The aim of this study was to investigate the rate of complications from ultrasound-guided axillary artery catheter placement in critically ill patients. METHODS: A retrospective study at a tertiary care center of patients admitted to an intensive care unit who had ultrasound-guided axillary artery catheter placement during admission. Primary outcome of interest was catheter related complications, including bleeding, vascular complications, compartment syndrome, stroke or air embolism, catheter malfunction, and need for surgical intervention. RESULTS: This study identified 88 patients who had an ultrasound-guided axillary artery catheter placed during their admission. Of these 88, nine patients required multiple catheters placed, for a total of 99 axillary artery catheter placement events. The median age was 64 [IQR 48, 71], 41 (47%) were female, and median body mass index (BMI) was 26 [IQR 22, 30]. The most common complication was minor bleeding (11%), followed by catheter malfunction (2%), and vascular complications (2%). Univariate analyses did not show any association between demographics and clinical variables, and complications related to axillary arterial catheter. CONCLUSION: The most common complication found with ultrasound-guided axillary artery catheter placement was minor bleeding, followed by catheter malfunction, and vascular complications. Ultrasound-guided axillary arterial catheters are an alternative in patients in whom radial or femoral arterial access is difficult or not possible to achieve.

8.
Surg Endosc ; 38(7): 3703-3715, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38782828

ABSTRACT

AIM: The benefits and short-term outcomes of transanal total mesorectal excision (taTME) for rectal cancer have been demonstrated previously, but questions remain regarding the oncologic outcomes following this challenging procedure. The purpose of this study was to analyze the oncologic outcomes following taTME at high-volume centers in the USA. METHODS: This was a multicenter, retrospective observational study of 8 tertiary care centers. All consecutive taTME cases for primary rectal cancer performed between 2011 and 2020 were included. Clinical, histopathologic, and oncologic data were analyzed. Primary endpoints were rate of local recurrence, distal recurrence, 3-year disease recurrence, and 3-year overall survival. Secondary endpoints included perioperative complications and TME specimen quality. RESULTS: A total of 391 patients were included in the study. The median age was 57 years (IQR: 49, 66), 68% of patients were male, and the median BMI was 27.4 (IQR: 24.1, 31.0). TME specimen was complete or near complete in 94.5% of cases and the rates of positive circumferential radial margin and distal resection margin were 2.0% and 0.3%, respectively. Median follow-up time was 30.7 months as calculated using reverse-KM estimator (CI 28.1-33.8) and there were 9 cases (2.5%) of local recurrence not accounting for competing risk. The 3-year estimated rate of disease recurrence was 19% (CI 15-25%) and the 3-year estimated overall survival was 90% (CI 87-94%). CONCLUSION: This large multicenter study confirms the oncologic safety and perioperative benefits of taTME for rectal cancer when performed by experienced surgeons at experienced referral centers.


Subject(s)
Neoplasm Recurrence, Local , Rectal Neoplasms , Transanal Endoscopic Surgery , Humans , Rectal Neoplasms/surgery , Rectal Neoplasms/pathology , Male , Middle Aged , Female , Retrospective Studies , Aged , United States/epidemiology , Transanal Endoscopic Surgery/methods , Neoplasm Recurrence, Local/epidemiology , Treatment Outcome , Margins of Excision , Proctectomy/methods , Postoperative Complications/epidemiology , Postoperative Complications/etiology
9.
J Bone Joint Surg Am ; 2024 May 10.
Article in English | MEDLINE | ID: mdl-38728379

ABSTRACT

BACKGROUND: Restoration of hand function after traumatic brachial plexus injury (BPI) remains a formidable challenge. Traditional methods such as nerve or free muscle transfers yield suboptimal results. Advancements in myoelectric prostheses, characterized by novel signal acquisition and improved material technology, show promise in restoring functional grasp. This study evaluated the ability of adults with a BPI injury to control an externally powered prosthetic hand using nonintuitive signals, simulating the restoration of grasp with a myoelectric prosthesis. It also assessed the effectiveness of a comprehensive multidisciplinary evaluation in guiding treatment decisions. METHODS: A multidisciplinary brachial plexus team assessed adults with compromised hand function due to BPI. The feasibility of amputation coupled with fitting of a myoelectric prosthesis for grasp reconstruction was evaluated. Participants' ability to control a virtual or model prosthetic hand using surface electromyography (EMG) as well as with contralateral shoulder motion-activated linear transducer signals was tested. The patient's input and injury type, along with the information from the prosthetic evaluation, were used to determine the reconstructive plan. The study also reviewed the number of participants opting for amputation and a myoelectric prosthetic hand for grasp restoration, and a follow-up survey was conducted to assess the impact of the initial evaluation on decision-making. RESULTS: Of 58 subjects evaluated, 47 (81%) had pan-plexus BPI and 42 (72%) received their initial assessment within 1 year post-injury. Forty-seven patients (81%) could control the virtual or model prosthetic hand using nonintuitive surface EMG signals, and all 58 could control it with contralateral uniscapular motion via a linear transducer and harness. Thirty patients (52%) chose and pursued amputation, and 20 (34%) actively used a myoelectric prosthesis for grasp. The initial evaluation was informative and beneficial for the majority of the patients, especially in demonstrating the functionality of the myoelectric prosthesis. CONCLUSIONS: The study indicates that adults with traumatic BPI can effectively operate a virtual or model myoelectric prosthesis using nonintuitive control signals. The simulation and multidisciplinary evaluation influenced informed treatment choices, with a high percentage of patients continuing to use the myoelectric prostheses post-amputation, highlighting its long-term acceptance and viability. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

10.
J Hand Surg Eur Vol ; : 17531934241247279, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38663874

ABSTRACT

A total of 26 adolescent patients were treated for scaphoid nonunion with a vascularized bone graft from either the medial femoral condyle or dorsal distal radius. There was an 85% union incidence, improved carpal alignment and a low incidence of complications.

11.
Cureus ; 16(3): e55848, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38590474

ABSTRACT

BACKGROUND: Despite evidence that ambulatory surgery is safe with faster recovery compared to in-patient hospitalization, surgeons in low- and middle-income countries like Uganda have been hesitant to embrace this practice. Kyabirwa Surgical Center (KSC) is the first freestanding ambulatory surgery center (ASC) in rural Uganda. We aim to report the impact of a rural ASC since its establishment, in alleviating surgically-treatable morbidity within its catchment area. METHODS: KSC is located in Jinja, Uganda. The center's electronic medical record was used to analyze the utilization of services, and the Uganda Bureau of Statistics was used to calculate KSC's catchment area. Effectiveness was calculated using disability-adjusted life years (DALYs) averted. RESULTS: Between July 2019 and December 2021, 7,391 patients (57.7% female, 42.3% male) visited KSC from a catchment area of 570,790 people. Of 1,355 procedures, 64.6% were general surgery, 21.3% endoscopy, 9.2% gynecological/genitourinary), 2.8% ENT, 1.5% colorectal, and 0.6% orthopedics. There were no postoperative hospital admissions for complications or mortalities. From the seven most common procedures with an associated disability weight, 2,193.16 total DALYs were averted. CONCLUSION: ASCs can be effective in addressing surgical care gaps in Uganda by increasing the yearly surgical capacity of the local catchment area and averting DALYs within the population.

12.
Plast Reconstr Surg ; 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38563524

ABSTRACT

BACKGROUND: Shoulder function following spinal nerve grafting in pan-brachial plexus injuries(Pan-BPI) is not well described. The purpose of this study was twofold: 1)to evaluate shoulder abduction(ABD) and external rotation(ER) after grafting of viable spinal nerves to the suprascapular nerve(SSN), axillary nerve(AxN), or posterior division of the upper trunk(PDUT); and 2)to determine patient characteristics, injury severity/characteristics, and nerve graft factors that influenced outcomes. METHODS: 362 Pan-BPI reconstruction patients from a single institution were reviewed for those who underwent spinal nerve grafting for shoulder reanimation between 2001 and 2018. Patient demographics, injury severity scores(ISS), graft characteristics, strength, range of motion for shoulder ABD and ER, and patient-reported outcomes were recorded. Patients were divided into three groups based on the recovery of shoulder function: no return, ABD only, and ABD and ER. RESULTS: 110 patients underwent spinal nerve grafting, with 41 meeting inclusion criteria. 17(41.5%) had no return of shoulder function, 14(34.1%) had ABD alone, and 10(24.4%) had ABD and ER. Patients with recovery of both ABD and ER were significantly younger(18.6±5.56), had lower BMI(22.4±4.0), and lower ISS(10.5±6.24, p=0.003). Multivariable analysis found that with increasing age(OR:0.786, 95%CI:0.576,0.941) and ISS(OR:0.820, 95%CI:0.606-0.979), odds for return of ABD and ER significantly decreased. CONCLUSIONS: In Pan-BPI, 24.4% of patients demonstrated return of both ABD and ER following spinal nerve grafting to SSN and either AxN or PDUT. Age, BMI, and ISS were associated with poorer recovery of shoulder function. Careful patient selection and consideration of age, BMI, and ISS may improve outcomes of spinal nerve grafting for shoulder reanimation. LEVEL OF EVIDENCE: III.

13.
Front Genet ; 15: 1396535, 2024.
Article in English | MEDLINE | ID: mdl-38660674
14.
Acta Crystallogr C Struct Chem ; 80(Pt 4): 129-142, 2024 04 01.
Article in English | MEDLINE | ID: mdl-38577890

ABSTRACT

This report presents a comprehensive investigation into the synthesis and characterization of Schiff base compounds derived from benzenesulfonamide. The synthesis process, involved the reaction between N-cycloamino-2-sulfanilamide and various substituted o-salicylaldehydes, resulted in a set of compounds that were subjected to rigorous characterization using advanced spectral techniques, including 1H NMR, 13C NMR and FT-IR spectroscopy, and single-crystal X-ray diffraction. Furthermore, an in-depth assessment of the synthesized compounds was conducted through Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) analysis, in conjunction with docking studies, to elucidate their pharmacokinetic profiles and potential. Impressively, the ADMET analysis showcased encouraging drug-likeness properties of the newly synthesized Schiff bases. These computational findings were substantiated by molecular properties derived from density functional theory (DFT) calculations using the B3LYP/6-31G* method within the Jaguar Module of Schrödinger 2023-2 from Maestro (Schrodinger LLC, New York, USA). The exploration of frontier molecular orbitals (HOMO and LUMO) enabled the computation of global reactivity descriptors (GRDs), encompassing charge separation (Egap) and global softness (S). Notably, within this analysis, one Schiff base, namely, 4-bromo-2-{N-[2-(pyrrolidine-1-sulfonyl)phenyl]carboximidoyl}phenol, 20, emerged with the smallest charge separation (ΔEgap = 3.5780 eV), signifying heightened potential for biological properties. Conversely, 4-bromo-2-{N-[2-(piperidine-1-sulfonyl)phenyl]carboximidoyl}phenol, 17, exhibited the largest charge separation (ΔEgap = 4.9242 eV), implying a relatively lower propensity for biological activity. Moreover, the synthesized Schiff bases displayed remarkeable inhibition of tankyrase poly(ADP-ribose) polymerase enzymes, integral in colon cancer, surpassing the efficacy of a standard drug used for the same purpose. Additionally, their bioavailability scores aligned closely with established medications such as trifluridine and 5-fluorouracil. The exploration of molecular electrostatic potential through colour mapping delved into the electronic behaviour and reactivity tendencies intrinsic to this diverse range of molecules.


Subject(s)
Colonic Neoplasms , Schiff Bases , Humans , Schiff Bases/chemistry , Models, Molecular , Molecular Conformation , Crystallography, X-Ray , Spectroscopy, Fourier Transform Infrared , Hydrogen Bonding , Phenols
15.
J Clin Neurol ; 20(2): 153-165, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38433485

ABSTRACT

Neurological diseases often manifest with neuropsychiatric symptoms such as depression, emotional incontinence, anger, apathy and fatigue. In addition, affected patients may also experience psychotic symptoms such as hallucinations and delusions. Various factors contribute to the development of psychotic symptoms, and the mechanisms of psychosis are similar, but still differ among various neurological diseases. Although psychotic symptoms are uncommon, and have been less well investigated, they may annoy patients and their families as well as impair the patients' quality of life and increase the caregiver burden. Therefore, we need to appropriately identify and treat these psychotic symptoms in patients with neurological diseases.

16.
J Hand Surg Am ; 49(6): 526-531, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38430093

ABSTRACT

PURPOSE: Pan-brachial plexus injury patients present a reconstructive challenge. The root analysis score, developed from parsimonious multivariable modeling of 311 pan-brachial plexus injury patients, determines the probability of having a viable C5 nerve based on four categories: positive C5 Tinel test, intact C5 nerve on computed tomography myelogram, lack of hemidiaphragmatic elevation, and absence of midcervical paraspinal fibrillations. METHODS: Root analysis scores were calculated for a separate cohort of patients with pan-brachial plexus injuries. Scores were validated by the presence or absence of a graftable C5 root, based on supraclavicular exploration and intraoperative electrophysiologic testing. Receiver operating characteristic curve, accuracy, and concordance statistic of the scores were calculated. Patients were divided into three root analysis score cohorts: less than 50 (low), 50-75 (average), and 75-100 points (high) based on dividing the score into quartiles and combining the lowest two. The probability, sensitivity, and specificity of each cohort having an available C5 nerve were based on the intraoperative assessment. RESULTS: Eighty patients (mean age, 33.1 years; 15 women and 65 men) were included. Thirty-one patients (39%) had a viable C5 nerve. The root analysis calculator had an overall accuracy of 82.5%, a receiver operating characteristic of 0.87, and a concordance statistic of 0.87, demonstrating high overall predictive value; 6.5% of patients with a score of less than 50 (94% sensitivity and 43% specificity), 16.1% of patients with a score of 50-75 (94% sensitivity and 67% specificity), and 77.4% of patients with a score of 75-100 (77% sensitivity and 90% specificity) had a graftable C5 nerve. CONCLUSIONS: The root analysis score demonstrated high accuracy and predictive power for a viable C5 nerve. In patients with a score of less than 50, the necessity of supraclavicular root exploration should balance patient factors, presentation timing, and concomitant injuries. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnosis II.


Subject(s)
Brachial Plexus , Spinal Nerve Roots , Humans , Female , Male , Adult , Brachial Plexus/injuries , Spinal Nerve Roots/diagnostic imaging , Middle Aged , ROC Curve , Brachial Plexus Neuropathies/surgery , Sensitivity and Specificity , Retrospective Studies
17.
J Hand Surg Eur Vol ; : 17531934241231170, 2024 Feb 19.
Article in English | MEDLINE | ID: mdl-38373612

ABSTRACT

Traumatic adult brachial plexus injuries typically cause immediate loss of upper limb function. Timely multidisciplinary treatment in specialized centres often results in a useful helper arm. Both the patient and the surgical team can benefit from an open discussion to set realistic expectations. Surgical reconstruction is customized for each patient, considering their injury factors and functional objectives. Optimizing pain control, adherence to procedure indications and using meticulous surgical techniques help minimize the risk of failing to meet the patient's goals. The need for potential alternative treatment(s) if the desired result is not achieved should be detailed before the initial reconstruction. This review discusses late treatment options, including tendon transfers, joint fusions, free functioning muscle transfers and prosthetics, for managing the failed primary reconstruction of the traumatic adult brachial plexus.

18.
J Biomol Struct Dyn ; : 1-14, 2024 Jan 08.
Article in English | MEDLINE | ID: mdl-38192072

ABSTRACT

We synthesized and characterized two copper(II) complexes: [CuL2Cl]Cl and [CuL'2Cl]Cl, where L = 2,2'-bipyridine and L' = 4,4'-dimethyl-2,2'-bipyridine. We evaluated their photocatalytic hydrocarboxylation properties on a series of synthesized Schiff bases (SBs): (E)-1-(4-((5-bromo-2-hydroxybenzylidene)amino)phenyl)ethanone (SB1), (E)-N-(4-(dimethylamino)benzylidene)benzo[d]thiazol-2-amine (SB2), (E)-4-Bromo-2-((thiazol-2-ylimino)methyl)phenol (SB3), and (E)-4-((5-bromo-2-hydroxybenzylidene)amino)-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one (SB4). Under mild photocatalytic reaction conditions (room temperature, 1 atm CO2, 30-watt Blue LED light), the derivatives of α-amino acids UAA1-4 were obtained with yields ranging from 5% to 44%. Experimental results demonstrated that [CuL2Cl]Cl exhibited superior photocatalytic efficiency compared to [CuL'2Cl]Cl, attributed to favourable electronic properties. In silico studies revealed strong binding strengths with E. faecalis DHFR (4M7U) for docked Schiff bases (SB) and unnatural α-amino acids (UAAs). In vitro studies further demonstrated significant antimicrobial and antifungal activity for SB2, SB3, and SB4, while none of the synthesized UAAs exhibited such properties, primarily due to the electronic and binding properties of these molecules.Communicated by Ramaswamy H. Sarma.

19.
J Biomol Struct Dyn ; 42(3): 1110-1125, 2024.
Article in English | MEDLINE | ID: mdl-37029762

ABSTRACT

The rationale at the basis of targeted approach in oncology is radically shifting-from development of highly specific agents aiming at a single target towards molecules interfering with multiple targets. This study was performed to isolate and characterize bioactive molecules from Olax subscorpioidea stem and investigate their potentials as multi-targeted inhibitors against selected non-small cell lung cancer, breast cancer and chronic myelogenous leukemia oncogenic targets. Three compounds: ß-sitosterol (1), α-amyrin (2) and stigmasterol (3) were isolated. The structures of 1 - 3 were elucidated by analysis of their spectroscopic data (NMR, MS and IR). To the best of our knowledge, this is the first time these compounds were isolated from O. subscorpioidea stems. Furthermore, integrated analysis of MS/MS data using the Global Natural Products Social Molecular Networking (GNPS) workflow enabled dereplication and identification of 26 compounds, including alkaloids (remerine, boldine), terpenoids (3-hydroxy-11-ursen-28,13-olide, oleanolic acid), flavonoids (kaempferitrin, olax chalcone A) and saponins in O. subscorpioidea stem. Molecular docking studies revealed that some of the compounds, including olax chalcone A (-9.2 to -10.9 kcal/mol), 3-Hydroxy-11-ursen-28,13-olide (-6.6 to -10.2 kcal/mol), α-amyrin (-6.6 to -10.2 kcal/mol), stigmasterol (-7.7 to -10.1 kcal/mol), ß-Sitosterol (-7 to -9.9 kcal/mol) and kaempferitrin (-7.7 to -9 kcal/mol) possessed good inhibitory potentials against selected cancer targets, when compared with reference inhibitors (-8.4 to -13.7 kcal/mol). A few of these compounds were shown to have considerable to favorable pharmacokinetic and drug-likeness properties. This study provides some rationale for the use of O. subscorpioidea in ethnomedicinal management of cancer and identifies some potential anticancer agents.Communicated by Ramaswamy H. Sarma.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Chalcone , Chalcones , Lung Neoplasms , Pentacyclic Triterpenes , Humans , Molecular Docking Simulation , Stigmasterol , Tandem Mass Spectrometry , Molecular Dynamics Simulation
20.
Ann Surg Oncol ; 31(3): 1970-1979, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37989953

ABSTRACT

BACKGROUND: Cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) improves survival compared with chemotherapy alone in patients with peritoneal carcinomatosis (PC) of colorectal (CRC) origin, however, long-term survival data are lacking. We report the actual survival of patients who underwent CRS/HIPEC for PC of CRC origin with a minimum potential 5-year follow-up period to identify factors that preclude long-term survival. METHODS: We performed a retrospective analysis of a prospective database, analyzing patients undergoing CRS/HIPEC for PC of CRC origin from 2007 to 2017. Patients with aborted CRS/HIPEC, postoperative follow-up <90 days, or non-CRC histology were excluded. Overall survival (OS) and disease-free survival (DFS) were measured from date of surgery. Surviving patients with <60 months of follow-up were censored at date of last follow-up. RESULTS: A total of 103 patients met inclusion criteria and were analyzed. CC score 0-1 was achieved in 89.3% of patients, and median peritoneal cancer index (PCI) was 9 (interquartile range [IQR] 5-17). Ninety-day mortality was 2.9%. The median follow-up of survivors was 88 months. Five-year OS was 36%, and median OS was 42.5 months. Factors independently associated with poor survival included high PCI (PCI = 14-20, hazard ratio [HR] 3.1, p = 0.007, and PCI > 20, HR 5.3, p ≤ 0.001) and incomplete CRS (CC score-2, HR 2.96, p = 0.02). Patients with low PCI (0-6) had 5-year OS 60.7%. CONCLUSIONS: Actual 5-year OS was 36% and median OS was 42.5 months. Our study demonstrates that patients with PC from CRC origin with low PCI who undergo complete surgical resection can achieve favorable long-term survival.


Subject(s)
Colorectal Neoplasms , Hyperthermia, Induced , Peritoneal Neoplasms , Humans , Peritoneal Neoplasms/therapy , Hyperthermic Intraperitoneal Chemotherapy , Combined Modality Therapy , Prognosis , Cytoreduction Surgical Procedures , Retrospective Studies , Colorectal Neoplasms/pathology , Survival Rate , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
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