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1.
Int J Educ Res ; 112: 101941, 2022.
Article in English | MEDLINE | ID: mdl-35136282

ABSTRACT

Research continues to emerge about the impact of COVID-19 on education; however, reports about the impact on students receiving special education services are more limited. This study examined parental views of distance learning for students with disabilities during the COVID-19 crisis. Using a survey disseminated via social media, we examined parents' views (N = 153) of PK-12 education for students receiving special education services during COVID-19. Results indicated three main themes: (1) special education and related service hours were decreased during virtual learning; (2) parents reported that their children were unable to participate in virtual learning without significant adult support; (3) parents often were unable to provide their children with assistance due to other commitments including work and childcare.

2.
J Immunol ; 203(7): 1897-1908, 2019 10 01.
Article in English | MEDLINE | ID: mdl-31484735

ABSTRACT

Sepsis is characterized as life-threatening organ dysfunction caused by a dysregulated host immune response to infection. The purpose of this investigation was to determine the differential effect of sepsis on innate versus adaptive immunity, in humans, by examining RNA expression in specific immune cell subsets, including monocytes/macrophages and CD4 and CD8 T cells. A second aim was to determine immunosuppressive mechanisms operative in sepsis that might be amenable to immunotherapy. Finally, we examined RNA expression in peripheral cells from critically ill nonseptic patients and from cancer patients to compare the unique immune response in these disorders with that occurring in sepsis. Monocytes, CD4 T cells, and CD8 T cells from septic patients, critically ill nonseptic patients, patients with metastatic colon cancer, and healthy controls were analyzed by RNA sequencing. Sepsis induced a marked phenotypic shift toward downregulation of multiple immune response pathways in monocytes suggesting that impaired innate immunity may be fundamental to the immunosuppression that characterizes the disorder. In the sepsis cohort, there was a much more pronounced effect on gene transcription in CD4 T cells than in CD8 T cells. Potential mediators of sepsis-induced immunosuppression included Arg-1, SOCS-1, and SOCS-3, which were highly upregulated in multiple cell types. Multiple negative costimulatory molecules, including TIGIT, Lag-3, PD-1, and CTLA-4, were also highly upregulated in sepsis. Although cancer had much more profound effects on gene transcription in CD8 T cells, common immunosuppressive mechanisms were present in all disorders, suggesting that immunoadjuvant therapies that are effective in one disease may also be efficacious in the others.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Gene Expression Regulation, Neoplastic/immunology , Monocytes/immunology , Neoplasms/immunology , RNA, Neoplasm/immunology , Sepsis/immunology , Sequence Analysis, RNA , Adult , Aged , CD4-Positive T-Lymphocytes/pathology , CD8-Positive T-Lymphocytes/pathology , Critical Illness , Female , Humans , Immune Tolerance , Male , Middle Aged , Monocytes/pathology , Neoplasm Proteins/genetics , Neoplasm Proteins/immunology , Neoplasms/genetics , Neoplasms/pathology , Prospective Studies , RNA, Neoplasm/genetics , Sepsis/genetics , Sepsis/pathology
3.
Cancers (Basel) ; 16(15)2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39123402

ABSTRACT

Multidisciplinary tumor boards (MTBs) facilitate decision-making among subspecialists in the care of oncology patients, but the mechanisms by which they enhance outcomes remain incompletely understood. Our aim was to measure the agreement between sarcoma MTBs and radiology reports' disease assessment and management recommendations. This single-center IRB-approved retrospective study evaluated cases presented at a weekly sarcoma MTB from 1 August 2020 to 31 July 2021. Cases without clinical notes, imaging studies, or radiology reports were excluded. The data collected included the patient's clinical status at the time of the MTB, the treatment response assessment by the MTB and radiologists (stable disease; partial response; complete response; progressive disease/recurrence), and the recommendations of the radiology reports and of the MTB. The agreement between the initial radiologist review and MTB on disease assessment and recommendations was analyzed using kappa statistics. In total, 283 cases met the inclusion criteria. Radiology reports provided recommendations in 34.3% of cases, which were adhered to by the ordering providers in 73.2% of cases. The agreement between MTBs and radiology reports was moderate in disease assessment (86.2% agreement; κ = 0.78; p < 0.0001) and negligible in recommendations (36% agreement; κ = 0.18; p < 0.0001). Radiologists were more likely to assign progressive disease/recurrence than MTBs (54.4% vs. 44.4%; p < 0.001) and to recommend short-term imaging follow-up more commonly than MTBs (46.4% vs. 21.7%; p < 0.001). At a tertiary care center, radiologists' isolated interpretations of imaging findings and management recommendations frequently differ from the MTB's consensus, reflecting the value of multidisciplinary discussions incorporating the patient's clinical status and the available treatment options into the final radiographic assessment.

4.
PLoS One ; 18(2): e0281442, 2023.
Article in English | MEDLINE | ID: mdl-36787300

ABSTRACT

Microbial nitrogen (N) cycling pathways are largely responsible for producing forms of N that are available for plant uptake or lost from the system as gas or leachate. The temporal dynamics of microbial N pathways in tropical agroecosystems are not well defined, even though they are critical to understanding the potential impact of soil conservation strategies. We aimed to 1) characterize temporal changes in functional gene associations across a seasonal gradient, 2) identify keystone genes that play a central role in connecting N cycle functions, and 3) detect gene co-occurrences that remained stable over time. Soil samples (n = 335) were collected from two replicated field trials in Rwanda between September 2020 and March 2021. We found high variability among N-cycle gene relationships and network properties that was driven more by sampling timepoint than by location. Two nitrification gene targets, hydroxylamine oxidoreductase and nitrite oxidoreductase, co-occurred across all timepoints, indicating that they may be ideal year-round targets to limit nitrification in rainfed agricultural soils. We also found that gene keystoneness varied across time, suggesting that management practices to enhance N-cycle functions such as the application of nitrification inhibitors could be adapted to seasonal conditions. Our results mark an important first step in employing gene networks to infer function in soil biogeochemical cycles, using a tropical seasonal gradient as a model system.


Subject(s)
Gene Regulatory Networks , Soil , Soil/chemistry , Soil Microbiology , Agriculture , Nitrification , Nitrogen/metabolism
5.
Brachytherapy ; 22(5): 649-654, 2023.
Article in English | MEDLINE | ID: mdl-37271655

ABSTRACT

OBJECTIVE: CivaSheet is a palladium-103, implantable, intraoperative radiation therapy device which emits unidirectional radiation that enables boost doses in patients who have otherwise received the maximum radiation dose. Here, we present our initial clinical experience with the first 10 cases using this new technology. METHODS AND MATERIALS: A retrospective chart review of all patients with STS treated with surgical resection and CivaSheet placement at the University of Miami Hospital, a tertiary care center, from January 2018 to December 2019, was performed. Adjuvant radiation was administered by a palladium-103 implant, which delivered an average of 47 Gy (35-55) to a depth of 5 mm. RESULTS: Nine patients underwent CivaSheet placement from January 2018 until December 2019 for a total of 10 CivaSheets placed (1 patient had 2 CivaSheets inserted) and followed for a mean of 27 months (4-45 months). Four tumors were located in the retroperitoneum, two in the chest, two in the groin, and two within the lower extremity. At the time of tumor resection and CivaSheet placement, tumor sizes ranged from 2.5 cm to 13.8 cm with an average of 7.6 cm. Four patients necessitated musculocutaneous tissue flaps for closure and reconstruction. All patients with Grade 4 complications had flap reconstruction and prior radiation. Four patients' tumors recurred locally for a local recurrence rate of 40%. Three patients had modified accordion Grade 4 complications necessitating additional surgery for CivaSheet removal. Extremity tumors unanimously developed modified accordion Grade 4 adverse events. CONCLUSIONS: CivaSheet may be an acceptable alternative treatment modality compared to prior brachytherapy methods.


Subject(s)
Brachytherapy , Sarcoma , Soft Tissue Neoplasms , Humans , Brachytherapy/methods , Retrospective Studies , Radioisotopes/therapeutic use , Sarcoma/radiotherapy , Sarcoma/surgery , Sarcoma/pathology , Soft Tissue Neoplasms/radiotherapy
6.
Ann Plast Surg ; 67(2): 106-8, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21407068

ABSTRACT

We present a case report of a 59-year-old patient with a giant lipoma of the left breast, extending to the left arm. She sought medical consultation because it had become heavy and caused pronounced breast asymmetry. The lesion was excised by means of an oncoplastic technique using the superior-medial pedicle wise-pattern breast reduction approach. We concluded that the use of the oncoplastic reduction pattern technique after removal of a giant breast lipoma is highly rewarding, resulting in a smaller-sized breast that is aesthetically more pleasing, has better symmetry with the contralateral breast, and provides relief from functional mass deficit. This technique minimizes the potential for a breast deformity once the tumor is resected.


Subject(s)
Breast Neoplasms/surgery , Lipoma/surgery , Mammaplasty/methods , Breast Neoplasms/diagnosis , Female , Humans , Lipoma/diagnosis , Middle Aged
7.
Microb Ecol ; 60(1): 192-205, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20574826

ABSTRACT

We compared the microbial community composition in soils from the Brazilian Amazon with two contrasting histories; anthrosols and their adjacent non-anthrosol soils of the same mineralogy. The anthrosols, also known as the Amazonian Dark Earths or terra preta, were managed by the indigenous pre-Colombian Indians between 500 and 8,700 years before present and are characterized by unusually high cation exchange capacity, phosphorus (P), and calcium (Ca) contents, and soil carbon pools that contain a high proportion of incompletely combusted biomass as biochar or black carbon (BC). We sampled paired anthrosol and unmodified soils from four locations in the Manaus, Brazil, region that differed in their current land use and soil type. Community DNA was extracted from sampled soils and characterized by use of denaturing gradient gel electrophoresis (DGGE) and terminal restriction fragment length polymorphism. DNA bands of interest from Bacteria and Archaea DGGE gels were cloned and sequenced. In cluster analyses of the DNA fingerprints, microbial communities from the anthrosols grouped together regardless of current land use or soil type and were distinct from those in their respective, paired adjacent soils. For the Archaea, the anthrosol communities diverged from the adjacent soils by over 90%. A greater overall richness was observed for Bacteria sequences as compared with those of the Archaea. Most of the sequences obtained were novel and matched those in databases at less than 98% similarity. Several sequences obtained only from the anthrosols grouped at 93% similarity with the Verrucomicrobia, a genus commonly found in rice paddies in the tropics. Sequences closely related to Proteobacteria and Cyanobacteria sp. were recovered only from adjacent soil samples. Sequences related to Pseudomonas, Acidobacteria, and Flexibacter sp. were recovered from both anthrosols and adjacent soils. The strong similarities among the microbial communities present in the anthrosols for both the Bacteria and Archaea suggests that the microbial community composition in these soils is controlled more strongly by their historical soil management than by soil type or current land use. The anthrosols had consistently higher concentrations of incompletely combusted organic black carbon material (BC), higher soil pH, and higher concentrations of P and Ca compared to their respective adjacent soils. Such characteristics may help to explain the longevity and distinctiveness of the anthrosols in the Amazonian landscape and guide us in recreating soils with sustained high fertility in otherwise nutrient-poor soils in modern times.


Subject(s)
Archaea/isolation & purification , Bacteria/isolation & purification , Biodiversity , Soil Microbiology , Soil/analysis , Agriculture , Archaea/genetics , Bacteria/genetics , Brazil , Cluster Analysis , DNA Fingerprinting , DNA, Archaeal/genetics , DNA, Bacterial/genetics , Polymorphism, Restriction Fragment Length , Sequence Analysis, DNA
8.
PLoS One ; 15(4): e0231032, 2020.
Article in English | MEDLINE | ID: mdl-32271795

ABSTRACT

The incorporation of cover crops into the maize (Zea mays L.)-soybean [Glycine max (L.) Merr.] rotation in the U.S. upper Midwest may improve sustainability. Long, cold winters in the region make identifying successful cover crop species and management practices a challenge. Two experiments were conducted in Minnesota, USA from fall 2016 through spring 2019 to examine the effect of cover crops interseeded at four- to six-leaf collar (early-interseeded) and dent to physiological maturity (late-interseeded) on biomass and grain yield of maize. Annual ryegrass (Lolium multiflorum L.) and cereal rye (Secale cereale L.) were evaluated as monocultures and in mixtures with crimson clover (Trifolium incarnatum L.) and forage radish (Raphanus sativus L.). Differences in canopy cover and biomass of late-interseeded cover crops were observed at the southernmost location in 2018. Additional accumulated growing-degree days in fall 2018 did not translate into increased cover crop canopy coverage of late-interseeded cover crops. Differences in cover crop canopy cover and biomass of early-interseeded cover crops were observed by fall frost at all locations in 2017 and at the northernmost location in 2018. Cover crop canopy cover and biomass at termination before planting maize, soil moisture at maize planting as well as maize aboveground biomass and yield were not affected by spring cereal rye regrowth of cover crops late-interseeded the previous year. Similarly, early-interseeded cover crops did not affect maize aboveground biomass or yield. We attribute these results to limited cover crop growth. This highlights the potential of a variety of cover crop strategies interseeded into maize in the U.S. upper Midwest; however, efforts to fine-tuning cover crop management and weather conditions are needed to benefit from such practice.


Subject(s)
Crop Production/methods , Crops, Agricultural/growth & development , Zea mays/growth & development , Biomass , Lolium/growth & development , Minnesota , Raphanus/growth & development , Secale/growth & development , Sustainable Development , Trifolium/growth & development
9.
J Am Coll Surg ; 231(2): 275-280, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32353399

ABSTRACT

Personal protective equipment (PPE) has been an invaluable yet limited resource when it comes to protecting healthcare workers against infection during the 2019 coronavirus (COVID-19) pandemic. In the US, N95 respirator supply chains are severely strained and conservation strategies are needed. A multidisciplinary team at the Washington University School of Medicine, Barnes Jewish Hospital, and BJC Healthcare was formed to implement a program to disinfect N95 respirators. The process described extends the life of N95 respirators using vaporized hydrogen peroxide (VHP) disinfection and allows healthcare workers to retain their own N95 respirator across a large metropolitan healthcare system.


Subject(s)
Coronavirus Infections/prevention & control , Disinfection/methods , Equipment Contamination/prevention & control , Hydrogen Peroxide/chemistry , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Masks/virology , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Academic Medical Centers , Betacoronavirus , COVID-19 , Coronavirus Infections/epidemiology , Humans , Masks/supply & distribution , Missouri/epidemiology , Pneumonia, Viral/epidemiology , SARS-CoV-2
10.
Front Microbiol ; 11: 509919, 2020.
Article in English | MEDLINE | ID: mdl-33042042

ABSTRACT

Drought is a critical factor limiting the productivity of legumes worldwide. Legumes can enter into a unique tripartite symbiotic relationship with root-nodulating bacteria of genera Rhizobium, Bradyrhizobium, or Sinorhizobium and colonization by arbuscular mycorrhizal fungi (AMF). Rhizobial symbiosis provides nitrogen necessary for growth. AMF symbiosis enhances uptake of diffusion-limited nutrients such as P, Zn, Cu, etc., and also water from the soil via plant-associated fungal hyphae. Rhizobial and AMF symbioses can act synergistically in promoting plant growth and fitness, resulting in overall yield benefits under drought stress. One of the approaches that rhizobia use to survive under stress is the accumulation of compatible solutes, or osmolytes, such as trehalose. Trehalose is a non-reducing disaccharide and an osmolyte reported to accumulate in a range of organisms. High accumulation of trehalose in bacteroids during nodulation protects cells and proteins from osmotic shock, desiccation, and heat under drought stress. Manipulation of trehalose cell concentrations has been directly correlated with stress response in plants and other organisms, including AMF. However, the role of this compound in the tripartite symbiotic relationship is not fully explored. This review describes the biological importance and the role of trehalose in the tripartite symbiosis between plants, rhizobia, and AMF. In particular, we review the physiological functions and the molecular investigations of trehalose carried out using omics-based approaches. This review will pave the way for future studies investigating possible metabolic engineering of this biomolecule for enhancing abiotic stress tolerance in plants.

11.
Sci Adv ; 6(24): eaay9691, 2020 06.
Article in English | MEDLINE | ID: mdl-32577507

ABSTRACT

Tumor heterogeneity and evolution drive treatment resistance in metastatic colorectal cancer (mCRC). Patient-derived xenografts (PDXs) can model mCRC biology; however, their ability to accurately mimic human tumor heterogeneity is unclear. Current genomic studies in mCRC have limited scope and lack matched PDXs. Therefore, the landscape of tumor heterogeneity and its impact on the evolution of metastasis and PDXs remain undefined. We performed whole-genome, deep exome, and targeted validation sequencing of multiple primary regions, matched distant metastases, and PDXs from 11 patients with mCRC. We observed intricate clonal heterogeneity and evolution affecting metastasis dissemination and PDX clonal selection. Metastasis formation followed both monoclonal and polyclonal seeding models. In four cases, metastasis-seeding clones were not identified in any primary region, consistent with a metastasis-seeding-metastasis model. PDXs underrepresented the subclonal heterogeneity of parental tumors. These suggest that single sample tumor sequencing and current PDX models may be insufficient to guide precision medicine.


Subject(s)
Clonal Evolution , Colonic Neoplasms , Animals , Clonal Evolution/genetics , Colonic Neoplasms/genetics , Disease Models, Animal , Exome/genetics , Genomics , Humans , Neoplasm Metastasis , Exome Sequencing
12.
Nat Commun ; 11(1): 2156, 2020 05 01.
Article in English | MEDLINE | ID: mdl-32358485

ABSTRACT

Colorectal cancer (CRC) is the most common gastrointestinal malignancy in the U.S.A. and approximately 50% of patients develop metastatic disease (mCRC). Despite our understanding of long non-coding RNAs (lncRNAs) in primary colon cancer, their role in mCRC and treatment resistance remains poorly characterized. Therefore, through transcriptome sequencing of normal, primary, and distant mCRC tissues we find 148 differentially expressed RNAs Associated with Metastasis (RAMS). We prioritize RAMS11 due to its association with poor disease-free survival and promotion of aggressive phenotypes in vitro and in vivo. A FDA-approved drug high-throughput viability assay shows that elevated RAMS11 expression increases resistance to topoisomerase inhibitors. Subsequent experiments demonstrate RAMS11-dependent recruitment of Chromobox protein 4 (CBX4) transcriptionally activates Topoisomerase II alpha (TOP2α). Overall, recent clinical trials using topoisomerase inhibitors coupled with our findings of RAMS11-dependent regulation of TOP2α supports the potential use of RAMS11 as a biomarker and therapeutic target for mCRC.


Subject(s)
Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Animals , Blotting, Western , Caco-2 Cells , Cell Line, Tumor , Chromatin Immunoprecipitation , Computational Biology , DNA Topoisomerases, Type II/metabolism , Disease Progression , Exons/genetics , Gene Expression Regulation, Neoplastic/drug effects , Gene Expression Regulation, Neoplastic/genetics , HCT116 Cells , HT29 Cells , Humans , Ligases/metabolism , Mice , Polycomb-Group Proteins/metabolism , RNA-Seq , Real-Time Polymerase Chain Reaction , Topoisomerase Inhibitors/pharmacology
13.
J Hepatobiliary Pancreat Sci ; 26(4): 137-143, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30821072

ABSTRACT

BACKGROUND: Patients can present with symptomatic gallbladder disease after cholecystectomy due to a remnant gallbladder. This is a rare problem and challenging diagnosis with limited prior characterization; thus, we present a large series of patients with a gallbladder remnant. METHODS: A retrospective review was performed of all patients presenting with symptomatic gallbladder remnant at a tertiary care center from 2002 to 2016. Data on presenting symptoms, diagnostic tests, treatments, and follow-up were collected. RESULTS: Thirty-one patients diagnosed and treated for a symptomatic gallbladder remnant were identified. The most common presenting symptoms included right upper quadrant pain (87%) and nausea (55%). The median time from symptom presentation to definitive diagnosis was 60 days. Diagnostic modalities utilized in the evaluation of these patients demonstrated that endoscopic retrograde cholangiopancreatography and magnetic resonance cholangiopancreatography were effective with sensitivities of 85% and 90%, respectively. Twenty-three (76.2%) patients underwent completion cholecystectomy, which proved to be definitive treatment. Additionally, eight (25.8%) patients were non-operative candidates and underwent endoscopic retrograde cholangiopancreatography and sphincterotomy, three of whom developed recurrent symptoms. CONCLUSION: A symptomatic gallbladder remnant after cholecystectomy is infrequently seen; however, the diagnosis should be considered in patients with recurrent biliary symptoms after cholecystectomy. Completion cholecystectomy can be challenging but is highly effective for definitive treatment.


Subject(s)
Gallbladder Diseases/diagnosis , Cholangiopancreatography, Endoscopic Retrograde , Cholangiopancreatography, Magnetic Resonance , Cholecystectomy , Humans , Retrospective Studies
14.
JCI Insight ; 4(19)2019 10 03.
Article in English | MEDLINE | ID: mdl-31527315

ABSTRACT

Aberrant activation of the NF-κB transcription factors underlies chemoresistance in various cancer types, including colorectal cancer (CRC). Targeting the activating mechanisms, particularly with inhibitors to the upstream IκB kinase (IKK) complex, is a promising strategy to augment the effect of chemotherapy. However, clinical success has been limited, largely because of low specificity and toxicities of tested compounds. In solid cancers, the IKKs are driven predominantly by the Toll-like receptor (TLR)/IL-1 receptor family members, which signal through the IL-1 receptor-associated kinases (IRAKs), with isoform 4 (IRAK4) being the most critical. The pathogenic role and therapeutic value of IRAK4 in CRC have not been investigated. We found that IRAK4 inhibition significantly abrogates colitis-induced neoplasm in APCMin/+ mice, and bone marrow transplant experiments showed an essential role of IRAK4 in immune cells during neoplastic progression. Chemotherapy significantly enhances IRAK4 and NF-κB activity in CRC cells through upregulating TLR9 expression, which can in turn be suppressed by IRAK4 and IKK inhibitors, suggesting a feed-forward pathway that protects CRC cells from chemotherapy. Lastly, increased tumor phospho-IRAK4 staining or IRAK4 mRNA expression is associated with significantly worse survival in CRC patients. Our results support targeting IRAK4 to improve the effects of chemotherapy and outcomes in CRC.


Subject(s)
Carcinogenesis/genetics , Colitis/metabolism , Colonic Neoplasms/metabolism , Colorectal Neoplasms/metabolism , Drug Resistance, Neoplasm/genetics , Interleukin-1 Receptor-Associated Kinases/metabolism , Animals , Bone Marrow Transplantation , Cell Line , Cell Survival/drug effects , Colitis/genetics , Colitis/pathology , Colon/pathology , Colonic Neoplasms/genetics , Colonic Neoplasms/pathology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Drug Resistance, Neoplasm/drug effects , Drug Therapy , Female , Gene Expression Regulation, Neoplastic , Genetic Predisposition to Disease/genetics , I-kappa B Kinase/genetics , Immunity, Innate , Interleukin-1 Receptor-Associated Kinases/antagonists & inhibitors , Interleukin-1 Receptor-Associated Kinases/genetics , Male , Mice , Mice, Inbred C57BL , NF-kappa B/metabolism , Protein Kinase Inhibitors/pharmacology , Signal Transduction , Toll-Like Receptor 9/metabolism , Toll-Like Receptors , Transcription Factors , Xenograft Model Antitumor Assays
15.
Surg Oncol Clin N Am ; 27(1): 121-140, 2018 01.
Article in English | MEDLINE | ID: mdl-29132556

ABSTRACT

Neoadjuvant endocrine therapy (NET) can be effective at downstaging patients with estrogen receptor-positive tumors and identifying those tumors that are endocrine sensitive and resistant. The optimal prognostic markers for stratification are under investigation. Use of NET will allow the identification of patients with estrogen receptor-positive tumors who might benefit from additional treatment and allow better understanding of endocrine resistance.


Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/drug therapy , Chemotherapy, Adjuvant/methods , Estrogen Receptor Modulators/therapeutic use , Neoadjuvant Therapy/methods , Female , Humans
16.
Oncoimmunology ; 7(9): e1470729, 2018.
Article in English | MEDLINE | ID: mdl-30228938

ABSTRACT

The tumor microenvironment (TME) represents a significant barrier to creating effective therapies for metastatic colorectal cancer (mCRC). In several malignancies, bone marrow derived CCR2+ inflammatory monocytes (IM) are recruited to the TME by neoplastic cells, where they become immunosuppressive tumor associated macrophages (TAM). Here we report that mCRC expression of the chemokine CCL2 facilitates recruitment of CCR2+ IM from the bone marrow to the peripheral blood. Immune monitoring of circulating monocytes in patients with mCRC found this influx was a prognostic biomarker and correlated with worse clinical outcomes. At the metastatic site, mCRC liver tumors were heavily infiltrated by TAM, which displayed a robust ability to dampen endogenous anti-tumor lymphocyte activity. Using a murine model of mCRC that recapitulates these findings from human disease, we show that targeting CCR2 reduces TAM accumulation in liver metastasis and restores anti-tumor immunity. Additional quantitative analysis of hepatic metastatic tumor burden and treatment efficacy found that administration of a small molecule CCR2 inhibitor (CCR2i) improves chemotherapeutic responses and increases overall survival in mice with mCRC liver tumors. Our study suggests that targeting the CCL2/CCR2 chemokine axis decreases TAM at the metastatic site, disrupting the immunosuppressive TME and rendering mCRC susceptible to anti-tumor T-cell responses.

17.
Orthop J Sports Med ; 5(5): 2325967117705319, 2017 May.
Article in English | MEDLINE | ID: mdl-28589156

ABSTRACT

BACKGROUND: Work-related rotator cuff injuries are a common cause of disability and employee time loss. PURPOSE: To examine the effectiveness of expedited rotator cuff surgery in injured workers who underwent rotator cuff decompression or repair and to explore the impact of demographic, clinical, and psychosocial factors in predicting the outcome of surgery. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Injured workers who were seen at a shoulder specialty program and who underwent expedited arthroscopic rotator cuff decompression or repair were observed for a period of 6 to 12 months based on their type of surgery and recovery trajectory. The primary outcome measure was the American Shoulder and Elbow Surgeons (ASES) Standardized Shoulder Assessment Form. The impact of surgery was assessed by whether the change in the ASES score exceeded the minimal clinically important difference (MCID) of 17 points. Secondary outcomes were range of motion (ROM), medication consumption, and work status. RESULTS: One hundred forty-six patients (43 women [29%], 103 men [71%]; mean age, 52 years; SD, 8 years) completed the study. Sixty-seven (46%) patients underwent rotator cuff repair. The mean time between the date the patient consented to have surgery and the date of surgery was 82 (SD, 44) days. There was a statistically significant improvement in ASES score and ROM and work status (52 returned to regular duties and 59 to modified duties) (P < .0001). Eighty-four percent (n = 122) of patients exceeded the MCID of 17 points. Individual factors that affected patient overall disability were preoperative ASES, work status prior to surgery, access to care, and autonomy at work. Achieving a minimal clinically meaningful change was influenced by perceived access to care, autonomy and stress at work, and overall satisfaction with the job. CONCLUSION: Expedited rotator cuff surgery improved disability, ROM, and work status in injured workers. Successful recovery after work-related shoulder injuries may further be facilitated by improving the psychosocial work environment and increasing access to care.

18.
J Hepatobiliary Pancreat Sci ; 23(7): 432-41, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27207482

ABSTRACT

BACKGROUND: The purpose of this report is to present results of the radical antegrade modular pancreatosplenectomy (RAMPS) procedure in 78 patients from a single center. METHODS: Seventy-eight patients had RAMPS procedure over 13 years. A database dealing with RAMPS for adenocarcinoma of the pancreas was constructed so that it could be converted into a set of tables. Each table covered one element of the subject. The database was populated from clinical records of patients who had a RAMPS procedure from 1999 to 2013. RESULTS: Fifty-six patients had anterior RAMPS and 22 had posterior RAMPS. Negative tangential margins were obtained in 94% of specimens. Overall the R0 rate was 85%. Mean lymph node count was 20. There were no 30-day or in-hospital mortalities but two patients died within 90 days. Pancreatic fistula and need for postoperative transfusion were the most common complications. Median survival was 24.6 months and 5-year overall actuarial survival was 25.1%. CONCLUSIONS: The RAMPS technique resulted in high negative tangential margin rates and good lymph node retrieval. The long-term survival result in 78 patients is probably an accurate reflection of what is possible with this tumor using this technique at this time.


Subject(s)
Adenocarcinoma/pathology , Adenocarcinoma/surgery , Pancreatectomy/methods , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgery , Splenectomy/methods , Adenocarcinoma/mortality , Adult , Aged , Blood Loss, Surgical , Cohort Studies , Databases, Factual , Disease-Free Survival , Female , Hospitals, University , Humans , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Operative Time , Pancreatectomy/mortality , Pancreatic Neoplasms/mortality , Postoperative Complications/mortality , Postoperative Complications/physiopathology , Prognosis , Retrospective Studies , Risk Assessment , Splenectomy/mortality , Survival Analysis , Treatment Outcome , United States
19.
J Robot Surg ; 8(2): 105-9, 2014 Jun.
Article in English | MEDLINE | ID: mdl-27637519

ABSTRACT

Laparoscopic treatment of benign esophageal conditions is technically complex with several inherent limitations. Robotic-assisted surgery provides technical improvement and helps to overcome some of these limitations. We therefore report a single surgeon's experience in management of benign esophageal diseases by robotic-assisted surgery. Over a period of 8 consecutive years, a retrospective chart review was performed of 105 patients who underwent robotic-assisted surgery for benign esophageal diseases by a single surgeon. Demographic data and outcome measures were studied. The robotic-assisted procedures included 85 Nissen fundoplications with and without mesh repair, 12 Heller myotomies and eight para-esophageal hernia repairs. The mean total operating time was lowest for the Nissen group (94 min) and highest for the para-esophageal group (183 min). Operating time decreased from a mean of 105 min in the first 20 cases to 84 min in the last 20 cases for the Nissen group (P = 0.014). The mean length of stay was 1.3, 1.6, 1.5 and 4.8 days for the groups, respectively. Persistent symptoms of dysphagia/reflux/dysphonia requiring further investigation were seen in nine (8 %) of these patients. Two of these patients required repeat Nissen fundoplication in the mesh group. Our complication rate, total operating time and length of stay for robotic-assisted benign esophageal surgery are comparable to those reported in the literature. When performed by an experienced surgeon, robotic-assisted surgery is safe and effective in the management of benign esophageal diseases.

20.
J Am Geriatr Soc ; 61(8): 1351-7, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23865843

ABSTRACT

OBJECTIVES: To evaluate long-term morbidity, mortality, and quality of life (QoL) after pancreaticoduodenectomy (PD) in elderly adults. DESIGN: Retrospective cohort study. SETTING: Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel. PARTICIPANTS: One hundred and sixty-eight individuals aged 70 and older who underwent PD between 1995 and 2010. MEASUREMENTS: A prospective pancreatic surgery database was analyzed for postoperative morbidity; mortality; intensive care unit (ICU), hospital, and rehabilitation facility stay; and readmissions after surgery. QoL was assessed using a validated questionnaire completed 3, 6, and 12 months after surgery. RESULTS: Seventy-two percent of the participants had an American Society of Anesthesiologists score of 3 or greater. There was no intraoperative death. Thirty- and 60-day postoperative mortality rates were 5.9% and 6.5%, respectively. Median ICU stay was 2 days, and median hospital stay was 22 days. Sixty-four participants (37.5%) were discharged to a rehabilitation facility. The first-year readmission rate was 31%. One- and 2-year overall survival rates were 58% and 36%, respectively. Global QoL scores 3 and 12 months after surgery were 68% and 73%, respectively. Scores were lower yet comparable with those of matched individuals undergoing laparoscopic cholecystectomy. CONCLUSION: Most elderly adults with pancreatic cancer survive longer than 1 year after PD; 36% survive longer than 2 years. These individuals are likely to have acceptable long-term morbidity and overall good QoL, corresponding with their age.


Subject(s)
Pancreatic Neoplasms/therapy , Pancreaticoduodenectomy/adverse effects , Pancreaticoduodenectomy/mortality , Postoperative Complications/mortality , Quality of Life , Aged , Aged, 80 and over , Chemoradiotherapy, Adjuvant , Cholecystectomy, Laparoscopic/adverse effects , Cholecystectomy, Laparoscopic/mortality , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Intensive Care Units/statistics & numerical data , Israel , Length of Stay/statistics & numerical data , Male , Pancreatic Neoplasms/mortality , Patient Readmission/statistics & numerical data , Prognosis , Rehabilitation Centers/statistics & numerical data , Surveys and Questionnaires , Utilization Review/statistics & numerical data
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