Publications by authors named "Tammy Lo"

23 Publications

  • Page 1 of 1

The longitudinal associations of physical activity, time spent outdoors in nature and symptoms of depression and anxiety during COVID-19 quarantine and social distancing in the United States.

Prev Med 2022 01 11;154:106863. Epub 2021 Nov 11.

Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, CA, USA.

Stressors associated with COVID-19 pandemic stay-at-home orders are associated with increased depression and anxiety and decreased physical activity. Given that physical activity and time spent outdoors in nature are associated with improved mental health, we examined the longitudinal association of these variables during the pandemic. Over 20,000 adults who participated in the U.S. Kaiser Permanente Research Bank, did not report COVID-19 symptoms, and responded to an online baseline and 3 follow-up surveys over approximately 3 months formed the cohort. Physical activity was assessed from a modified survey, time spent outdoors was assessed from one question, and anxiety and depression scores were assessed from validated instruments. Almost 60% were women, 82.8% were non-Hispanic white, and more than 93% of respondents were over the age of 50. Less in-person contact with friends and visiting crowded places was highly prevalent (>80%) initially and decreased somewhat (>70%). Participants in the lowest physical activity category (no physical activity) had the highest depression and anxiety scores compared to each successive physical activity category (p < 0.001). Spending less time outdoors was associated with higher depression and anxiety scores. This effect was greater for participants in the younger age categories compared with older age categories. The effect of less time spent outdoors on anxiety (p = 0.012) and depression (p < 0.001) scores was smaller for males than females. Results suggest that physical activity and time outdoors is associated with better mental health. People should be encouraged to continue physical activity participation during public health emergencies.
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http://dx.doi.org/10.1016/j.ypmed.2021.106863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8717103PMC
January 2022

Daily transient coating of the intestine leads to weight loss and improved glucose tolerance.

Metabolism 2022 01 21;126:154917. Epub 2021 Oct 21.

Laboratory for Surgical and Metabolic Research, Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Division of General and GI Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. Electronic address:

Introduction: Roux-en-Y gastric bypass surgery (RYGB) has been shown to be the gold standard treatment for obesity associated type-2-diabetes (T2D), however many T2D patients do not qualify or are reluctant to proceed with surgery due to its potential risks and permanent changes to GI anatomy. We have previously described a novel oral formulation, LuCI, that provides a transient coating of the proximal bowel and mimics the effects of RYGB. Herein, we aim to investigate the outcome of chronic LuCI administration on weight and glucose homeostasis.

Methods: Sprague-Dawley rats on a high fat diet achieving diet-induced obesity (DIO) received 5 weeks of daily LuCI or normal saline as control (n = 8/group). Daily weights and glucose tolerance were monitored throughout the experiment. At 5 weeks, systemic blood was sampled through a surgically placed jugular vein catheter, before and during an intestinal glucose bolus, to investigate changes in key hormones involved in glucose metabolism. To elucidate the effects of LuCI on nutrient absorption, fecal output and food intake were measured simultaneously with the analysis of homogenized stool samples performed using bomb calorimetry.

Results: At 5 weeks, LuCI animals weighted 8.3% less and had lower fasting glucose levels than Controls (77.6 ± 3.8 mg/dl vs. 99.1 ± 2.7 mg/dl, P < 0.001). LuCI-treated animals had lower baseline insulin and HOMA-IR. Post-prandially, LuCI group had increased GLP-1 and GIP secretion following a glucose challenge. Serum lipid analysis revealed lowered LDL levels highlighting the potential to not only improve glucose control but also modify cardiovascular risk. We then investigated whether LuCI's effect on proximal bowel exclusion may play a role in energy balance. Bomb calorimetry analysis suggested that LuCI reduced calorie absorption with no difference in caloric consumption.

Conclusion: We demonstrated that LuCI recapitulates the physical and hormonal changes seen after RYGB and can ameliorate weight gain and improve insulin sensitivity in a DIO rat model. Since LuCI's effect is transient and without systemic absorption, LuCI has the potential to be a novel therapy for overweight or obese T2D patients.
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http://dx.doi.org/10.1016/j.metabol.2021.154917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8666968PMC
January 2022

Facilitators and barriers to clinical practice guideline-consistent supportive care at pediatric oncology institutions: a Children's Oncology Group study.

Implement Sci Commun 2021 Sep 16;2(1):106. Epub 2021 Sep 16.

Research Institute, The Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Canada.

Background: Clinical practice guideline (CPG)-consistent care improves patient outcomes, but CPG implementation is poor. Little is known about CPG implementation in pediatric oncology. This study aimed to understand supportive care CPG implementation facilitators and barriers at pediatric oncology National Cancer Institute (NCI) Community Oncology Research Program (NCORP) institutions.

Methods: Healthcare professionals at 26 pediatric, Children's Oncology Group-member, NCORP institutions were invited to participate in face-to-face focus groups. Serial focus groups were held until saturation of ideas was reached. Supportive care CPG implementation facilitators and barriers were solicited using nominal group technique (NGT), and implementation of specific supportive care CPG recommendations was discussed. Notes from each focus group were analyzed using a directed content analysis. The top five themes arising from an analysis of NGT items were identified, first from each focus group and then across all focus groups.

Results: Saturation of ideas was reached after seven focus groups involving 35 participants from 18 institutions. The top five facilitators of CPG implementation identified across all focus groups were organizational factors including charging teams with CPG implementation, individual factors including willingness to standardize care, user needs and values including mentorship, system factors including implementation structure, and implementation strategies including a basis in science. The top five barriers of CPG implementation identified were organizational factors including tolerance for inconsistencies, individual factors including lack of trust, system factors including administrative hurdles, user needs and values including lack of inclusivity, and professional including knowledge gaps.

Conclusions: Healthcare professionals at pediatric NCORP institutions believe that organizational factors are the most important determinants of supportive care CPG implementation. They believe that CPG-consistent supportive care is most likely to be delivered in organizations that prioritize evidence-based care, provide structure and resources to implement CPGs, and eliminate implementation barriers.

Trial Registration: ClinicalTrials.gov Identifier: NCT02847130. Date of registration: July 28, 2016.
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http://dx.doi.org/10.1186/s43058-021-00200-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447588PMC
September 2021

Early Changes in Immune Cell Count, Metabolism, and Function Following Sleeve Gastrectomy: A Prospective Human Study.

J Clin Endocrinol Metab 2022 Jan;107(2):e619-e630

Laboratory for Surgical and Metabolic Research, Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Objective: To characterize longitudinal changes in blood biomarkers, leukocyte composition, and gene expression following laparoscopic sleeve gastrectomy (LSG).

Background: LSG is an effective treatment for obesity, leading to sustainable weight loss and improvements in obesity-related comorbidities and inflammatory profiles. However, the effects of LSG on immune function and metabolism remain uncertain.

Methods: Prospective data were collected from 23 enrolled human subjects from a single institution. Parameters of weight, comorbidities, and trends in blood biomarkers and leukocyte subsets were observed from preoperative baseline to 1 year postsurgery in 3-month follow-up intervals. RNA sequencing was performed on pairs of whole blood samples from the first 6 subjects of the study (baseline and 3 months postsurgery) to identify genome-wide gene expression changes associated with undergoing LSG.

Results: LSG led to a significant decrease in mean total body weight loss (18.1%) at 3 months and among diabetic subjects a reduction in hemoglobin A1c. Improvements in clinical inflammatory and hormonal biomarkers were demonstrated as early as 3 months after LSG. A reduction in neutrophil-lymphocyte ratio was observed, driven by a reduction in absolute neutrophil counts. Gene set enrichment analyses of differential whole blood gene expression demonstrated that after 3 months LSG induced transcriptomic changes not only in inflammatory cytokine pathways but also in several key metabolic pathways related to energy metabolism.

Conclusions: LSG induces significant changes in the composition and metabolism of immune cells as early as 3 months postoperatively. Further evaluation is required of bariatric surgery's effects on immunometabolism and the consequences for host defense and metabolic disease.
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http://dx.doi.org/10.1210/clinem/dgab673DOI Listing
January 2022

Genomic Classification and Clinical Outcome in Rhabdomyosarcoma: A Report From an International Consortium.

J Clin Oncol 2021 09 24;39(26):2859-2871. Epub 2021 Jun 24.

Department of Pediatrics, Seattle Children's Hospital, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA.

Purpose: Rhabdomyosarcoma is the most common soft tissue sarcoma of childhood. Despite aggressive therapy, the 5-year survival rate for patients with metastatic or recurrent disease remains poor, and beyond fusion status, no genomic markers are available for risk stratification. We present an international consortium study designed to determine the incidence of driver mutations and their association with clinical outcome.

Patients And Methods: Tumor samples collected from patients enrolled on Children's Oncology Group trials (1998-2017) and UK patients enrolled on malignant mesenchymal tumor and RMS2005 (1995-2016) trials were subjected to custom-capture sequencing. Mutations, indels, gene deletions, and amplifications were identified, and survival analysis was performed.

Results: DNA from 641 patients was suitable for analyses. A median of one mutation was found per tumor. In fusion-negative cases, mutation of any RAS pathway member was found in > 50% of cases, and 21% had no putative driver mutation identified. (15%), (15%), and (13%) mutations were found at a higher incidence than previously reported and mutations were associated with worse outcomes in both fusion-negative and fusion-positive cases. Interestingly, mutations in isoforms predominated in infants < 1 year (64% of cases). Mutation of was associated with histologic patterns beyond those previously described, older age, head and neck primary site, and a dismal survival. Finally, we provide a searchable companion database (ClinOmics), containing all genomic variants, and clinical annotation including survival data.

Conclusion: This is the largest genomic characterization of clinically annotated rhabdomyosarcoma tumors to date and provides prognostic genetic features that refine risk stratification and will be incorporated into prospective trials.
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http://dx.doi.org/10.1200/JCO.20.03060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425837PMC
September 2021

Restored TDCA and valine levels imitate the effects of bariatric surgery.

Elife 2021 06 22;10. Epub 2021 Jun 22.

Division of Transplant Surgery & Transplant Surgery Research Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, United States.

Background: Obesity is widespread and linked to various co-morbidities. Bariatric surgery has been identified as the only effective treatment, promoting sustained weight loss and the remission of co-morbidities.

Methods: Metabolic profiling was performed on diet-induced obese (DIO) mice, lean mice, and DIO mice that underwent sleeve gastrectomies (SGx). In addition, mice were subjected to intraperitoneal (i.p.) injections with taurodeoxycholic acid (TDCA) and valine. Indirect calorimetry was performed to assess food intake and energy expenditure. Expression of appetite-regulating hormones was assessed through quantification of isolated RNA from dissected hypothalamus tissue. Subsequently, i.p. injections with a melanin-concentrating hormone (MCH) antagonist and intrathecal administration of MCH were performed and weight loss was monitored.

Results: Mass spectrometric metabolomic profiling revealed significantly reduced systemic levels of TDCA and L-valine in DIO mice. TDCA and L-valine levels were restored after SGx in both human and mice to levels comparable with lean controls. Systemic treatment with TDCA and valine induced a profound weight loss analogous to effects observed after SGx. Utilizing indirect calorimetry, we confirmed reduced food intake as causal for TDCA/valine-mediated weight loss via a central inhibition of the MCH.

Conclusions: In summary, we identified restored TDCA/valine levels as an underlying mechanism of SGx-derived effects on weight loss. Of translational relevance, TDCA and L-valine are presented as novel agents promoting weight loss while reversing obesity-associated metabolic disorders.

Funding: This work has been supported in part by a grant from NIH (UO-1 A1 132898 to S.G.T., DP and MA). M.Q. was supported by the IFB Integrated Research and Treatment Centre Adiposity Diseases (Leipzig, Germany) and the German Research Foundation (QU 420/1-1). J.I. was supported by the Biomedical Education Program (BMEP) of the German Academic Exchange Service (DAAD). T.H. (HE 7457/1-1) and F.K. (KR 4362/1-1) were supported by the German Research Foundation (DFG). H.R.C.B. was supported the Swiss Society of Cardiac Surgery. Y.N. was supported by the Chinese Scholarship Council (201606370196) and Central South University. H.U., T.M. and R.M. were supported by the Osaka Medical Foundation. C.S.F. was supported by the German Research Foundation (DFG, SFB738, B3).
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http://dx.doi.org/10.7554/eLife.62928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257250PMC
June 2021

Validation of healthcare professional proxy-reported children's International Mucositis Evaluation Scale.

Oral Dis 2021 May 15. Epub 2021 May 15.

Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada.

Objective: The objective was to describe the reliability and validity of the healthcare professional proxy-report version of the Children's International Mucositis Evaluation Scale (ChIMES).

Methods: We included pediatric patients who were between 4 and 21 years of age and scheduled to undergo hematopoietic cell transplantation. Mucositis was evaluated by trained healthcare professionals who scored ChIMES, the World Health Organization oral toxicity scale, mouth, and throat pain visual analogue scale, National Cancer Institute-Common Terminology Criteria and the Oral Mucositis Daily Questionnaire. Measures were completed daily and evaluated on days 7-17 post-stem cell infusion for this analysis. Psychometric properties examined were internal consistency, test-retest reliability (days 13 and 14), and convergent construct validity.

Results: There were 192 participants included. Cronbach's alpha was 0.90 for ChIMES Total Score and 0.93 for ChIMES Percentage Score. Test-retest reliability were as follows: intraclass correlation coefficient (ICC) 0.82 (95% confidence interval (CI) 0.77-0.85) for ChIMES Total Score and ICC 0.82 (95% CI 0.77-0.86) for ChIMES Percentage Score. In terms of construct validation, all correlations between measures met or exceeded those hypothesized (all p < 0.05).

Conclusions: The healthcare professional proxy-report version of ChIMES is reliable and valid for children and adolescents undergoing hematopoietic cell transplantation.
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http://dx.doi.org/10.1111/odi.13918DOI Listing
May 2021

Musculoskeletal impairments in children receiving intensive therapy for acute leukemia or undergoing hematopoietic stem cell transplant: A report from the Children's Oncology Group.

Pediatr Blood Cancer 2021 08 23;68(8):e29053. Epub 2021 Apr 23.

Division of Hematology Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada.

Background: Children receiving intensive chemotherapy for leukemia or undergoing hematopoietic stem cell transplant (HSCT) for solid tumors or leukemia are at risk for musculoskeletal (MSK) impairment from their underlying disease and from treatment. Data are limited on the incidence and nature of these disorders during intensive therapy. This study's objective was to provide a cross-sectional description of MSK impairments in this population.

Procedure: Children with acute myeloid leukemia (AML), relapsed acute lymphoblastic leukemia (rALL), or undergoing HSCT were systematically assessed for MSK impairments as part of Children's Oncology Group study ACCL0934. Assessments occurred at study entry, at 2 months, and at 12 months and included evaluation for signs or symptoms of MSK impairment and the type, site, and diagnosis.

Results: Six hundred three patients were included. MSK signs or symptoms were present in 48 (8.0%) children at study entry, 64 (13.5%) children at 2 months, and 40 (11.6%) children at 12 months. Arthralgia and/or gait abnormalities were the most common impairments; the knee was the most common site. Arthritis and tendonitis were both rare. Vincristine neuropathy, MSK impacts from central nervous system pathology, and bone or joint pain from underlying cancer were the most common diagnoses. Multivariate analysis demonstrated that having rALL (odds ratio [OR] 2.00, 95% CI 1.07-3.76, p = .03) or obesity (OR 2.10, 95% CI 1.12-3.95, p = .02) were risk factors for MSK impairment at study entry.

Conclusions: MSK impairments are common in this intensively treated patient population, especially in those with rALL and those who are obese.
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http://dx.doi.org/10.1002/pbc.29053DOI Listing
August 2021

Glycemic Control as an Early Prognostic Marker in Advanced Pancreatic Cancer.

Front Oncol 2021 25;11:571855. Epub 2021 Feb 25.

Department of Medicine, Norwalk Hospital, Nuvance Health, Norwalk, CT, United States.

Purpose: Impaired glucose metabolism is present in most patients with pancreatic ductal adenocarcinoma (PDAC). Whereas previous studies have focused on pre-treatment glycemic indices and prognosis in those with concomitant diabetes, the effects of glycemic control during chemotherapy treatment on prognosis, in patients with and without diabetes, have not been well characterized. We examined the relationship between early glycemic control and overall survival (OS) in a cohort of patients with advanced PDAC treated in a community setting.

Patients And Methods: Seventy-three patients with advanced PDAC (38% with diabetes) receiving chemotherapy while participating in a biobanking clinical trial were included. Clinical characteristics and laboratory results during 1 year were obtained from the electronic medical record. Kaplan-Meier estimate, log-rank test and hazard ratios were computed to assess the effect of glycemic control on OS. The Cox proportional hazards regression model was applied to ascertain the significance of glycemic control with other survival variables.

Results: One thousand four hundred eighteen random blood glucose (RBG) values were analyzed. In accord with previous findings, a 50% decline in the serum tumor marker CA 19-9 at any time was predictive of survival (=0.0002). In univariate analysis, an elevated pre-treatment average RBG, 3-month average RBG (RBG-3) and the FOLFIRINOX regimen were associated with longer survival. Based on ROC analysis (AUC=0.82), an RBG-3 of 120 mg/dl was determined to be the optimal cutoff to predict 12-month survival. In multivariate analysis that included age, stage, BMI, performance status, presence of diabetes, and chemotherapy regimen, only RBG-3 maintained significance: an RBG-3 ≤120 mg/dl predicted for improved OS compared to >120 mg/dl (19 9 months; HR=0.37, =0.002). In contrast, an early decline in CA 19-9 could not predict OS.

Conclusion: Lower glucose levels during the first 3 months of treatment for advanced PDAC predict for improved OS in patients both with and without diabetes. These results suggest that RBG-3 may be a novel prognostic biomarker worthy of confirmation in a larger patient cohort and that studies exploring a possible cause and effect of this novel survival-linked relationship are warranted.
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http://dx.doi.org/10.3389/fonc.2021.571855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947820PMC
February 2021

Germline Cancer Predisposition Variants in Pediatric Rhabdomyosarcoma: A Report From the Children's Oncology Group.

J Natl Cancer Inst 2021 Jul;113(7):875-883

Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, TX, USA.

Background: Several cancer-susceptibility syndromes are reported to underlie pediatric rhabdomyosarcoma (RMS); however, to our knowledge there have been no systematic efforts to characterize the heterogeneous genetic etiologies of this often-fatal malignancy.

Methods: We performed exome-sequencing on germline DNA from 615 patients with newly diagnosed RMS consented through the Children's Oncology Group. We compared the prevalence of cancer predisposition variants in 63 autosomal-dominant cancer predisposition genes in these patients with population controls (n = 9963). All statistical tests were 2-sided.

Results: We identified germline cancer predisposition variants in 45 RMS patients (7.3%; all FOXO1 fusion negative) across 15 autosomal dominant genes, which was statistically significantly enriched compared with controls (1.4%, P = 1.3 × 10-22). Specifically, 73.3% of the predisposition variants were found in predisposition syndrome genes previously associated with pediatric RMS risk, such as Li-Fraumeni syndrome (TP53) and neurofibromatosis type I (NF1). Notably, 5 patients had well-described oncogenic missense variants in HRAS (p.G12V and p.G12S) associated with Costello syndrome. Also, genetic etiology differed with histology, as germline variants were more frequent in embryonal vs alveolar RMS patients (10.0% vs 3.0%, P = .02). Although patients with a cancer predisposition variant tended to be younger at diagnosis (P = 9.9 × 10-4), 40.0% of germline variants were identified in those older than 3 years of age, which is in contrast to current genetic testing recommendations based on early age at diagnosis.

Conclusions: These findings demonstrate that genetic risk of RMS results from germline predisposition variants associated with a wide spectrum of cancer susceptibility syndromes. Germline genetic testing for children with RMS should be informed by RMS subtypes and not be limited to only young patients.
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http://dx.doi.org/10.1093/jnci/djaa204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246828PMC
July 2021

Early changes in immune cell metabolism and function are a hallmark of sleeve gastrectomy: a prospective human study.

medRxiv 2020 Nov 3. Epub 2020 Nov 3.

Objective: To characterize longitudinal changes in blood biomarkers, leukocyte composition, and gene expression following laparoscopic sleeve gastrectomy (LSG).

Background: LSG is an effective treatment for obesity, leading to sustainable weight loss and improvements in obesity-related co-morbidities and inflammatory profiles. However, the effects of LSG on immune function and metabolism remain uncertain.

Methods: Prospective data was collected from 23 enrolled human subjects from a single institution. Parameters of weight, co-morbidities, and trends in blood biomarkers and leukocyte subsets were observed from pre-operative baseline to one year in three-month follow-up intervals. RNA-sequencing was performed on pairs of whole blood samples from the first six subjects of the study (baseline and three months post-surgery) to identify genome-wide gene expression changes associated with undergoing LSG.

Results: LSG led to a significant decrease in mean total body weight loss (18.1%) at three months and among diabetic subjects a reduction in HbA1c. Improvements in clinical inflammatory and hormonal biomarkers were demonstrated as early as three months after LSG. A reduction in neutrophil-lymphocyte ratio was observed, driven by a reduction in absolute neutrophil counts. Gene set enrichment analyses of differential whole blood gene expression demonstrated that after three months, LSG induced transcriptomic changes not only in inflammatory cytokine pathways but also in several key metabolic pathways related to energy metabolism.

Conclusions: LSG induces significant changes in the composition and metabolism of immune cells as early as three months post-operatively. Further evaluation is required of bariatric surgery's effects on immunometabolism and consequences for host defense and metabolic disease.
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http://dx.doi.org/10.1101/2020.07.31.20161687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654921PMC
November 2020

ATM-Mutated Pancreatic Cancer: Clinical and Molecular Response to Gemcitabine/Nab-Paclitaxel After Genome-Based Therapy Resistance.

Pancreas 2020 01;49(1):143-147

Department of Medicine, Norwalk Hospital, Nuvance Health, Norwalk, CT.

Metastatic pancreatic cancer (PC) is an aggressive malignancy, with most patients deriving benefit only from first-line chemotherapy. Increasingly, the recommended treatment for those with a germline mutation in a gene involved in homologous recombination repair is with a platinum drug followed by a poly (ADP-ribose) polymerase (poly adenosine phosphate-ribose polymerase [PARP]) inhibitor. Yet, this is based largely on studies of BRCA1/2 or PALB2 mutated PC. We present the case of a 44-year-old woman with ATM-mutated PC who achieved stable disease as the best response to first-line fluorouracil, leucovorin, irinotecan, and oxaliplatin, followed by progression on a PARP inhibitor. In the setting of jaundice, painful hepatomegaly, and a declining performance status, she experienced rapid disease regression with the nonplatinum regimen, gemcitabine plus nab-paclitaxel. Both physical stigmata and abnormal laboratory values resolved, imaging studies showed a reduction in metastases and her performance status returned to normal. Measurement of circulating tumor DNA for KRAS G12R by digital droplet polymerase chain reaction confirmed a deep molecular response. This case highlights that first-line treatment with a platinum-containing regimen followed by PARP inhibition may not be the best choice for individuals with ATM-mutated pancreatic cancer. Additional predictors of treatment response are needed in this setting.
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http://dx.doi.org/10.1097/MPA.0000000000001461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946099PMC
January 2020

Short-Term Outcomes of Inflammatory Bowel Disease after Roux-en-Y Gastric Bypass vs Sleeve Gastrectomy.

J Am Coll Surg 2019 06 21;228(6):893-901.e1. Epub 2019 Feb 21.

Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. Electronic address:

Background: Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are the most effective therapies for obesity and may have beneficial effects on the immune system. Therefore, we compared RYGB vs SG outcomes in patients with inflammatory bowel disease (IBD).

Study Design: In this retrospective cohort study, we identified 54 patients with either Crohn's disease (CD; n = 31) or ulcerative colitis (UC; n = 23), diagnosed before bariatric surgery, between 2000 and 2017. Nineteen patients underwent RYGB and 35 patients underwent SG.

Results: Patients presenting for RYGB and SG were of similar age (46.2 ± 9.5 years vs 47.2 ± 12.3 years), preoperative BMI (48.5 ± 7.7 kg/m vs 44.9 ± 7.3 kg/m) and IBD status, as measured by medications. Both operations led to significant weight loss at 1 year. After RYGB and SG, there were no significant differences in the proportion of patients with UC who had improved (27% vs 8%), unchanged (64% vs 92%), or worse (9% vs 0%) IBD medication requirements, respectively. Similar analysis in the patients with CD showed no significant differences in the proportion who had improved (37.5% vs 44%), or unchanged (25% vs 52%) IBD-medication requirements after RYGB and SG, respectively. However, there was a significant difference in the proportion of patients who had worsened CD after RYGB compared with SG (37.5% vs 4%; p = 0.016). There was a greater rate of surgical complications after RYGB compared to SG (26% vs. 3%; p = 0.02).

Conclusions: A sizable proportion of patients experienced improvements in IBD post-bariatric surgery. However, in CD patients, RYGB was associated with a significantly greater number of patients with increased IBD-medication requirements. Sleeve gastrectomy led to less weight loss, but had a lower rate of severe complications compared with RYGB. In patients with IBD, and particularly CD, SG may be the safer surgery.
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http://dx.doi.org/10.1016/j.jamcollsurg.2019.01.021DOI Listing
June 2019

The role of colonoscopy and CT colonography in patients presenting with symptoms of constipation.

Br J Radiol 2017 May 3;90(1073):20160147. Epub 2017 Mar 3.

General Surgery Department, Epsom and St Helier University Hospitals NHS Trust, Carshalton, UK.

Objective: There is controversy whether constipation as a primary presenting complaint is an indication for diagnostic colonoscopy. CT colonography (CTC) is a less invasive and more acceptable alternative. We compared the completion and sensitivity of colonoscopy with CTC in patients who presented with the primary symptom of constipation.

Methods: A retrospective study was conducted which examined the first 100 colonoscopies and 100 CTCs carried out for the primary symptom of constipation from June 2012 to December 2013. The primary outcome measure was failure rate of the investigations. Secondary outcomes included reasons for failure and comparison of cost effectiveness between the two modalities.

Results: A total of 200 patients were included in this study. Of these, the first consecutive 100 colonoscopies and 100 CTCs were included. One colonic cancer was detected in each of the CTC and the colonoscopy arm, respectively. 37 (37%) attempted colonoscopies were incomplete examinations. The most common reasons were discomfort (51.4%) and poor bowel preparation (27%). There was no failure of CTC. For 100 patients, CTC as a primary investigation was a more cost-effective investigation (p ≤ 0.01) costing £55,016 as compared with colonoscopy costing £73,666.

Conclusion: There is an unacceptably high failure rate of colonoscopy in patients who presented with the primary symptom of constipation. Hence, we propose that CTC may be an acceptable first-line investigation with a further colonoscopy/flexible sigmoidoscopy if lesions are detected. Advances in knowledge: First study to examine the use of CTC in patients with constipation.
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http://dx.doi.org/10.1259/bjr.20160147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605095PMC
May 2017

A rare presentation of complication arising from Meckel's diverticulum in the form of diverticulotransverse colonic fistula in an adult.

BMJ Case Rep 2015 Jun 3;2015. Epub 2015 Jun 3.

Ashford and St Peter's NHS Trust, Surrey, UK.

Meckel's diverticulum is a common congenital malformation of the gastrointestinal tract, reported to be present in 2-4% of the population. Although most patients with Meckel's diverticulum remain asymptomatic throughout life, reports of acute inflammation, perforation, haemorrhage, intussusception, intestinal obstruction, vesicodiverticular fistulae and primary tumours are described. We present a rare diagnosis of diverticulotransverse colonic fistula and its management.
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http://dx.doi.org/10.1136/bcr-2013-203330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4460404PMC
June 2015

Acute lower back pain mapped by dermatomal scarification in urban Malawi.

BMJ Case Rep 2012 Nov 30;2012. Epub 2012 Nov 30.

Department of Trauma and Orthopaedics, Queen Elizabeth Hospital, Woolwich, London, UK.

Lower back pain is a problem that affects many and generates an economic burden on the National Health Service. In modern days, although it is tempting to rely on specialist imaging for the initial investigation of back pain, it is often unnecessary. Comprehensive clinical examination is immediately available and should detect neurological impairments where they exist. A 32-year-old man from Malawi presented to clinic with lower back pain radiating to the right leg. Inspection revealed traditional scarification marks along the classical path of lumbar nerve root, which coincided with his L5 dermatomal pain. The distribution of his 'Mphini' along the typical path of lumbar nerve was identical to his myelography. This report strongly illustrates that in the Western medical setting, accurate history and examination would have allowed correct interpretation of these symptoms and correctly indicated the need for myelography.
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http://dx.doi.org/10.1136/bcr-11-2010-3529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4542432PMC
November 2012

Does muscle-sparing thoracotomy as opposed to posterolateral thoracotomy result in better recovery?

Interact Cardiovasc Thorac Surg 2013 Jan 9;16(1):60-7. Epub 2012 Oct 9.

Department of Cardiothoracic Surgery, Suez Canal University Hospital, Ismailia, Egypt.

A best evidence topic was written according to a structured protocol. The question addressed was whether muscle-sparing thoracotomy (MST), as opposed to posterolateral thoracotomy (PLT), results in better recovery. A total of 108 papers were found using the reported searches of which eight represented the best evidence to answer the clinical question. The authors, date, journal, study type, population, main outcome measures and results are tabulated. A recent large prospective, randomized, double-blinded, controlled study demonstrated a shorter length of stay in patients undergoing MST. It failed to demonstrate any significant difference in pain reported or pulmonary function. A separate prospective randomized controlled trial focussed on pain, pulmonary function, late shoulder range of motion and late muscle strength. It failed to show any significant difference in these domains between PLT and MST. While the mean 'opening time' is greater when performing a MST, this is negated by a shorter mean 'closing time' when compared with PLT. Overall, the evidence suggests that MST results in greater early (1 week) preservation of skeletal muscle strength and range of motion over PLT. This difference has disappeared at 1 month. There is little evidence to suggest a difference in pulmonary function or pain dependent on the thoracotomy type. Moreover, analgesic consumption is similar. However, there is an inverse relationship between the incision length and the post-thoracotomy syndrome.
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http://dx.doi.org/10.1093/icvts/ivs295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3523615PMC
January 2013

Can pregnant women be safely placed on cardiopulmonary bypass?

Interact Cardiovasc Thorac Surg 2012 Dec 3;15(6):1063-70. Epub 2012 Sep 3.

Department of Cardiothoracic Surgery, Wythenshawe Hospital, Manchester, UK.

A best evidence topic was written according to a structured protocol. The question addressed was whether cardiopulmonary bypass can be used safely with satisfactory maternal and foetal outcomes in pregnant patients undergoing cardiac surgery. A total of 679 papers were found using the reported searches of which 14 represented the best evidence to answer the clinical question. The authors, date, journal, study type, population, main outcome measures and results are tabulated. Reported measures were maternal and foetal mortality and complications, mode of delivery, cardiopulmonary bypass and aortic cross-clamp times, perfusate flow rate and temperature and maternal NYHA functional class. The most recent of the best evidence studies, a retrospective observational study of 21 pregnant patients reported early and late maternal mortalities of 4.8 and 14.3%, respectively, and a foetal mortality of 14.3%. Median cardiopulmonary bypass and aortic cross-clamp times were 53 and 35 min, respectively, and the median bypass temperature was 37°C. Three larger retrospective reviews of the literature reported maternal mortality rates of 2.9-5.1% and foetal mortality rates of 19-29%. Mean cardiopulmonary bypass times ranged from 50.5 to 77.8 min. Another retrospective observational study reported maternal mortality of 13.3% and foetal mortality of 38.5%. Mean cardiopulmonary bypass and aortic cross-clamp times were 89.1 and 62.8 min, respectively, with a mean bypass temperature of 31.8°C. A retrospective case series reported no maternal mortality and one case of foetal mortality. Median cardiopulmonary bypass and aortic cross-clamp times were 101 and 88 min, respectively. Eight case reports described 10 patients undergoing cardiopulmonary bypass. There were no reports of maternal mortality and one report of foetal mortality. Mean cardiopulmonary bypass and aortic cross-clamp times were 105 and 50 min, respectively. We conclude that while the use of cardiopulmonary bypass during pregnancy poses a high risk for both the mother and the foetus, the use of high-flow, high-pressure, pulsatile, normothermic bypass and continuous foetal and uterine monitoring can allow cardiac surgery with the use of cardiopulmonary bypass to be performed with the greatest control of risk in the pregnant patient.
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http://dx.doi.org/10.1093/icvts/ivs318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501292PMC
December 2012

Is there benefit in smoking cessation prior to cardiac surgery?

Interact Cardiovasc Thorac Surg 2012 Oct 2;15(4):726-32. Epub 2012 Jul 2.

Department of Cardiothoracic Surgery, Wythenshawe Hospital, Manchester, UK.

A best evidence topic was written according to a structured protocol. The question addressed was whether smoking cessation prior to cardiac surgery would result in a greater freedom from postoperative complications. A total of 564 papers were found using the reported searches, of which five represented the best evidence to answer the clinical question. The authors, date, journal, study type, population, main outcome measures and results are tabulated. Reported measures were operative mortality, pulmonary complications, infective complications, neurological complications, transfusion requirements, duration of ventilation, intensive care unit and hospital stay, intensive care unit re-admission, postoperative gas exchange parameters and postoperative pulmonary function. The largest of the best evidence studies demonstrated a significant reduction in pulmonary complications in non-smokers (P < 0.001); however, there was an increased requirement for transfusion in this cohort (P = 0.002). There were non-significant reductions in neurological complications, infective complications and re-admissions to intensive care. Another large cohort study demonstrated significant reductions in non-smokers in mortality (P < 0.0001), pulmonary complications (P = 0.0002), infection (P < 0.0007), intensive care unit re-admission (P = 0.0002), duration of mechanical ventilation (P = 0.026) and intensive care unit stay (P = 0.002). A larger cohort study again demonstrated significant reductions in non-smokers in pulmonary complications (P < 0.002), duration of mechanical ventilation (P < 0.012) and intensive care unit stay (P < 0.005). A smaller prospective cohort study reported significantly raised PaO(2) (P = 0.0091) and reduced PaCO(2) (P < 0.0001) levels in the non-smokers as well as improved FVC and FEV(1) (P < 0.0001). There were also reductions in duration of intubation (P < 0.0001), intensive care unit stay (P < 0.0001) and hospital stay (P < 0.0013). Another small cohort study reporting outcomes of heart transplantation demonstrated significant improvement in non-smokers in terms of survival (P = 0.031), duration of intubation (P = 0.05) and intensive care unit stay (P = 0.021). We conclude that there is strong evidence demonstrating superior outcomes in non-smokers following cardiac surgery and advocate the necessity of smoking cessation as soon as possible prior to cardiac surgery.
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http://dx.doi.org/10.1093/icvts/ivs177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3445343PMC
October 2012

Spontaneous rupture of utero-ovarian vessels in pregnancy.

BMJ Case Rep 2012 May 30;2012. Epub 2012 May 30.

Department of Women's Health, William Harvey Hospital, Kent, UK.

Spontaneous rupture of utero-ovarian vessels in pregnancy is rare and usually involves utero-ovarian veins. Presenting symptoms include acute-onset abdominal pain and maternal hypovolemic shock secondary to haemoperitoneum. Although this condition had been documented over a century ago, an accurate diagnosis is rarely reached prior to laparotomy due to a multitude of other surgical and obstetrical presentations that may pose a similar clinical picture. In such an event an emergency exploratory laparotomy followed by caesarean section with ligation of the uterine vessels can help in preventing a maternal mortality.
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http://dx.doi.org/10.1136/bcr.02.2012.5904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4542847PMC
May 2012

What is the role of screening in the management of abdominal aortic aneurysms?

Interact Cardiovasc Thorac Surg 2012 Apr 19;14(4):399-405. Epub 2012 Jan 19.

Department of Surgery, Poole General Hospital, Poole, UK.

A best-evidence topic in vascular surgery was written according to a structured protocol. The question addressed was whether screening asymptomatic individuals for an abdominal aortic aneurysm (AAA) is feasible and improves disease-free survival. Seven studies presented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results and limitations of the studies are tabulated. In total, four randomized population-based studies have evaluated ultrasound screening for AAA: two British studies, Multicentre Aneurysm Screening Study (MASS) and the Chichester trial, and one each in Viborg County, Denmark and Western Australia. Participants were randomized to receive an invitation to screen or not. The MASS trial randomized 67 770 men, followed participants over 10 years and concluded that screening would almost half AAA-related deaths in men aged 65-74 years. The smaller Chichester trial included only 6040 men but demonstrated a 42% reduction in AAA-related mortality at 5 years, with ongoing benefit at 15 years (11% reduction). The Viborg County trial recruited 12 639 men aged 64-73 years, showed a 66% reduction in AAA-related mortality over 14 years. Finally, the Western Australia trial evaluated 41 000 men but included an older population of 65-83 years old. No benefit was seen in this age group but subgroup analysis of men aged 65-74 showed a significant mortality benefit. Only a small or insignificant benefit in all-cause mortality was seen in any of these studies. A recent meta-analysis of these trials has shown a significant benefit in AAA-related mortality in the long term and concluded that AAA screening is superior to other established screening programmes. The cost-effectiveness of screening was assessed in the MASS and Viborg County trials and was found to be substantially below the cost threshold set by the National Institute of Clinical Excellence for acceptance of interventions. Quality of life was assessed in the MASS and in a case-control study and showed no adverse effects that outweigh the benefits. We concluded that ultrasound screening for AAAs has met all the criteria to become a screening programme and would substantially reduce disease-related death with no adverse effect on quality of life.
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http://dx.doi.org/10.1093/icvts/ivr106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3309812PMC
April 2012

Should a patent foramen ovale found incidentally during isolated coronary surgery be closed?

Interact Cardiovasc Thorac Surg 2011 May 22;12(5):794-8. Epub 2011 Feb 22.

Department of Cardiothoracic Surgery, The London Chest Hospital, Bonner Road, London E2 9JX, UK.

A best evidence topic was written according to a structured protocol. The question addressed was whether incidentally found patent foramen ovale (PFO) during isolated coronary surgery should be closed. A total of 573 papers were found using the reported searches of which six represented the best evidence to answer the clinical question. The authors, date, journal, study type, population, main outcome measures and results are tabulated. There is currently no evidence to suggest that incidental PFO in patients undergoing cardiac surgery is linked with increased morbidity, mortality or decreased long-term survival. The most significant study identified examined the outcomes of 2277 patients with incidentally found PFO during cardiac surgery of whom 639 underwent closure. After propensity matched analysis, the authors found closure was associated with a significantly higher risk of postoperative stroke with no advantage in terms of long-term survival. A recent survey of 438 cardiac surgeons from the USA showed no consensus on decision-making behind closure, but that factors taken in to account include PFO size, right atrial pressure and a history of paradoxical embolism. This is not surprising given that morphological research has confirmed that larger PFO size is indeed associated with cryptogenic stroke.
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http://dx.doi.org/10.1510/icvts.2011.265835DOI Listing
May 2011

Improvised straight needle suture passer.

Ann R Coll Surg Engl 2010 Mar;92(2):172

Department of Trauma and Orthopaedics, Queen Elizabeth Hospital, Woolwich, London, UK.

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http://dx.doi.org/10.1308/003588410x12628812459058hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3025227PMC
March 2010
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