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1.
Palliat Med ; 38(2): 170-183, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37424275

ABSTRACT

BACKGROUND: Several clinician training interventions have been developed in the past decade to address serious illness communication. While numerous studies report on clinician attitudes and confidence, little is reported on individual education modalities and their impact on actual behavior change and patient outcomes. AIM: To examine what is known about the education modalities used in serious illness communication training and their impact on clinician behaviors and patient outcomes. DESIGN: A scoping review using the Joanna Briggs Methods Manual for Scoping Reviews was conducted to examine studies measuring clinician behaviors or patient outcomes. DATA SOURCES: Ovid MEDLINE and EMBASE databases were searched for English-language studies published between January 2011 and March 2023. RESULTS: The search identified 1317 articles: 76 met inclusion criteria describing 64 unique interventions. Common education modalities used were: single workshop (n = 29), multiple workshops (n = 11), single workshop with coaching (n = 7), and multiple workshops with coaching (n = 5); though they were inconsistently structured. Studies reporting improved clinician skills tended to be in simulation settings with neither clinical practice nor patient outcomes explored. While some studies reported behavior changes or improved patient outcomes, they did not necessarily confirm improvements in clinician skills. As multiple modalities were commonly used and often embedded within quality improvement initiatives, the impact of individual modalities could not be determined. CONCLUSION: This scoping review of serious illness communication interventions found heterogeneity among education modalities used and limited evidence supporting their effectiveness in impacting patient-centered outcomes and long-term clinician skill acquisition. Well-defined educational modalities and consistent measures of behavior change and standard patient-centered outcomes are needed.


Subject(s)
Attitude , Communication , Humans , Outcome Assessment, Health Care , Clinical Competence , Health Personnel/education
2.
Article in English | MEDLINE | ID: mdl-38092258

ABSTRACT

PURPOSE: SABR is increasingly used to treat renal cell carcinoma (RCC). However, the optimal method to assess treatment response is unclear. We aimed to quantify changes in both volume and maximum linear size of tumors after SABR and evaluate the utility of the 2 approaches in treatment response assessment. METHODS AND MATERIALS: We retrospectively studied patients with RCC treated with SABR at our institution between 2013 and 2020. All available follow-up computed tomography scans were aligned, and tumors were contoured on all scans. Volume and maximum linear size were measured at each follow-up, relative to these measurements at the time of computed tomography simulation. RESULTS: Twenty-four patients with 25 tumors were included. Median follow-up was 32 months (range, 16-67). Nineteen tumors (76%) had 30% volumetric response at a median time of 7 months after SABR, and 12 tumors (48%) had 30% decrease in maximum linear size at a median time of 16 months. Eighteen tumors (72%) decreased in volume on first follow-up scan and continued to shrink, and 5 tumors (20%) displayed transient growth after SABR (average 24% increase in volume). Compared with T1a tumors, T1b or larger tumors were more likely to have transient growth (8% vs 33%; P = .16) and had higher average relative volume 24 months after SABR (0.47 vs 0.8; P = .022). CONCLUSIONS: Volume measurement results in more pronounced and earlier change compared with linear size measurement when assessing response to SABR. These findings may provide guidance when assessing treatment response for patients with RCC treated with SABR.

3.
Curr Oncol ; 30(9): 8602-8611, 2023 09 20.
Article in English | MEDLINE | ID: mdl-37754539

ABSTRACT

Primary central nervous system lymphoma (PCNSL) is primarily treated with combination chemotherapy, while whole-brain radiotherapy (WBRT) can be used as consolidative treatment or as a salvage option for central nervous system (CNS) relapse. We investigated whether fractionated stereotactic radiosurgery (fSRS) could replace WBRT in cases where patients had poor performance status or minimal disease at the time of consolidation, to spare patients the adverse effects of WBRT. We retrospectively identified 10 patients who completed 14 courses of fSRS for PCNSL or for CNS relapse of systemic lymphoma. Of 14 fSRS treatments, there were 10 distant brain recurrences among 6 patients, occurring on average 13.6 months after fSRS. A total of 4 of the 10 recurrences were treated with further fSRS, and 4 were treated with WBRT. There was one late in-field recurrence after both fSRS and WBRT, which occurred 27 months after fSRS. The median survival after fSRS was 36 months, and side effects after fSRS were minimal. This case series represents a potential treatment option for patients with CNS lymphoma, for whom WBRT is indicated but where the toxic effects of this treatment would be prohibitive.


Subject(s)
Radiosurgery , Humans , Retrospective Studies , Brain , Central Nervous System
4.
BMJ Case Rep ; 15(5)2022 May 04.
Article in English | MEDLINE | ID: mdl-35508353

ABSTRACT

The simultaneous diagnosis of colonic lymphoma and adenocarcinoma in the same location is rare and presents challenges in its treatment considerations, especially in elderly patients. While previous cases have been described, there is little consistency in treatment regimens, and outcomes are generally poor. We describe the case of a man in his late 80s who presented with primary cecal and colonic B cell lymphoma, treated with R-mini-CHOP chemotherapy, but was found to have a residual adenocarcinoma in the cecum after treatment that was then successfully resected. The patient remains alive and well 3 years postoperation. This case highlights the need to consider lymphoma as a possible diagnosis for any colonic mass, and the need to consider rebiopsy of residual abnormal-appearing tissue postchemotherapy to confirm the diagnosis. Moreover, our report affirms that aggressive, curative-intent treatment with age-adjusted chemotherapy, and subsequent surgical resection is feasible for certain elderly patients with dual malignant diagnoses.


Subject(s)
Adenocarcinoma , Colonic Neoplasms , Lymphoma, B-Cell , Lymphoma , Adenocarcinoma/diagnosis , Adenocarcinoma/drug therapy , Adenocarcinoma/surgery , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colonic Neoplasms/drug therapy , Colonic Neoplasms/pathology , Colonic Neoplasms/surgery , Cyclophosphamide/therapeutic use , Doxorubicin/therapeutic use , Humans , Lymphoma/drug therapy , Lymphoma, B-Cell/drug therapy , Male , Prednisone/therapeutic use , Vincristine/therapeutic use
5.
Proc Natl Acad Sci U S A ; 113(12): 3245-50, 2016 Mar 22.
Article in English | MEDLINE | ID: mdl-26951669

ABSTRACT

Rotary ATPases couple ATP synthesis or hydrolysis to proton translocation across a membrane. However, understanding proton translocation has been hampered by a lack of structural information for the membrane-embedded a subunit. The V/A-ATPase from the eubacterium Thermus thermophilus is similar in structure to the eukaryotic V-ATPase but has a simpler subunit composition and functions in vivo to synthesize ATP rather than pump protons. We determined the T. thermophilus V/A-ATPase structure by cryo-EM at 6.4 Å resolution. Evolutionary covariance analysis allowed tracing of the a subunit sequence within the map, providing a complete model of the rotary ATPase. Comparing the membrane-embedded regions of the T. thermophilus V/A-ATPase and eukaryotic V-ATPase from Saccharomyces cerevisiae allowed identification of the α-helices that belong to the a subunit and revealed the existence of previously unknown subunits in the eukaryotic enzyme. Subsequent evolutionary covariance analysis enabled construction of a model of the a subunit in the S. cerevisae V-ATPase that explains numerous biochemical studies of that enzyme. Comparing the two a subunit structures determined here with a structure of the distantly related a subunit from the bovine F-type ATP synthase revealed a conserved pattern of residues, suggesting a common mechanism for proton transport in all rotary ATPases.


Subject(s)
Adenosine Triphosphatases/metabolism , Biological Evolution , Cryoelectron Microscopy/methods , Models, Biological , Saccharomyces cerevisiae/enzymology , Thermus thermophilus/enzymology
6.
Elife ; 4: e10180, 2015 Oct 06.
Article in English | MEDLINE | ID: mdl-26439008

ABSTRACT

Adenosine triphosphate (ATP), the chemical energy currency of biology, is synthesized in eukaryotic cells primarily by the mitochondrial ATP synthase. ATP synthases operate by a rotary catalytic mechanism where proton translocation through the membrane-inserted FO region is coupled to ATP synthesis in the catalytic F1 region via rotation of a central rotor subcomplex. We report here single particle electron cryomicroscopy (cryo-EM) analysis of the bovine mitochondrial ATP synthase. Combining cryo-EM data with bioinformatic analysis allowed us to determine the fold of the a subunit, suggesting a proton translocation path through the FO region that involves both the a and b subunits. 3D classification of images revealed seven distinct states of the enzyme that show different modes of bending and twisting in the intact ATP synthase. Rotational fluctuations of the c8-ring within the FO region support a Brownian ratchet mechanism for proton-translocation-driven rotation in ATP synthases.


Subject(s)
Cryoelectron Microscopy , Mitochondrial Proton-Translocating ATPases/chemistry , Animals , Cattle , Computational Biology , Imaging, Three-Dimensional , Mitochondrial Proton-Translocating ATPases/genetics , Models, Molecular , Protein Conformation , Protein Folding
7.
J Mol Biol ; 426(9): 1936-46, 2014 May 01.
Article in English | MEDLINE | ID: mdl-24560694

ABSTRACT

Bacterial pathogens require iron for proliferation and pathogenesis. Pseudomonas aeruginosa is a prevalent Gram-negative opportunistic human pathogen that takes advantage of immunocompromised hosts and encodes a number of proteins for uptake and utilization of iron. Here we report the crystal structures of PhuS, previously known as the cytoplasmic heme-trafficking protein from P. aeruginosa, in both the apo- and the holo-forms. In comparison to its homologue ChuS from Escherichia coli O157:H7, the heme orientation is rotated 180° across the α-γ axis, which may account for some of the unique functional properties of PhuS. In contrast to previous findings, heme binding does not result in an overall conformational change of PhuS. We employed spectroscopic analysis and CO measurement by gas chromatography to analyze heme degradation, demonstrating that PhuS is capable of degrading heme using ascorbic acid or cytochrome P450 reductase-NADPH as an electron donor and produces five times more CO than ChuS. Addition of catalase slows down but does not stop PhuS-catalyzed heme degradation. Through spectroscopic and mass spectrometry analysis, we identified the enzymatic product of heme degradation to be verdoheme. These data taken together suggest that PhuS is a potent heme-degrading enzyme, in addition to its proposed heme-trafficking function.


Subject(s)
Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Heme/metabolism , Pseudomonas aeruginosa/enzymology , Biotransformation , Carbon Monoxide/analysis , Chromatography, Gas , Crystallography, X-Ray , Escherichia coli O157/enzymology , Heme/analogs & derivatives , Models, Molecular , Protein Binding , Protein Conformation , Spectrum Analysis
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