Publications by authors named "Jonathan Carter"

146 Publications

Tissue engineered skeletal muscle model of rheumatoid arthritis using human primary skeletal muscle cells.

J Tissue Eng Regen Med 2021 Nov 15. Epub 2021 Nov 15.

Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA.

Rheumatoid arthritis (RA) is a chronic inflammatory disease primarily targeting the joints. Autoreactive immune cells involved in RA affect other tissues, including skeletal muscle. Patients with RA experience diminished physical function, limited mobility, reduced muscle function, chronic pain, and increased mortality. To explore the impact of RA on skeletal muscle, we engineered electrically responsive, contractile human skeletal muscle constructs (myobundles) using primary skeletal muscle cells isolated from the vastus lateralis muscle of 11 RA patients (aged 57-74) and 10 aged healthy donors (aged 55-76), as well as from the hamstring muscle of six young healthy donors (less than 18 years of age) as a benchmark. Since all patients were receiving treatment for the disease, RA disease activity was mild. In 2D culture, RA myoblast purity, growth rate, and senescence were not statistically different than aged controls; however, RA myoblast purity showed greater variance compared to controls. Surprisingly, in 3D culture, contractile force production by RA myobundles was greater compared to aged controls. In support of this finding, assessment of RA myofiber maturation showed increased area of sarcomeric α-actinin (SAA) expression over time compared to aged controls. Furthermore, a linear regression test indicated a positive correlation between SAA protein levels and tetanus force production in RA and controls. Our findings suggest that medications prescribed to RA patients may maintain-or even enhance-muscle function, and this effect is retained and observed in in vitro culture. Future studies regarding the effects of RA therapeutics on RA skeletal muscle, in vivo and in vitro, are warranted.
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http://dx.doi.org/10.1002/term.3266DOI Listing
November 2021

ASMBS position statement on preoperative patient optimization before metabolic and bariatric surgery.

Surg Obes Relat Dis 2021 Dec 3;17(12):1956-1976. Epub 2021 Sep 3.

Clinical Issues Committee, American Society of Metabolic and Bariatric Surgeons; Department of Clinical Surgery, University of California-San Francisco, San Francisco, California.

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http://dx.doi.org/10.1016/j.soard.2021.08.024DOI Listing
December 2021

Optimal Surgical Treatment for Type 2 Diabetes: Sleeve Gastrectomy or Gastric Bypass?

Adv Surg 2021 09 6;55:1-8. Epub 2021 Jul 6.

Department of Surgery, University of California - San Francisco, 513 Parnassus Avenue, HSW1601, San Francisco, CA 94143, USA. Electronic address:

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http://dx.doi.org/10.1016/j.yasu.2021.05.001DOI Listing
September 2021

Study of the Interaction of an Iron Phthalocyanine Complex over Surface Modified Carbon Nanotubes.

Materials (Basel) 2021 Jul 21;14(15). Epub 2021 Jul 21.

Departamento Química Inorgánica y Técnica, Facultad de Ciencias UNED, Paseo Senda del Rey No. 9, 28040 Madrid, Spain.

Carbon nanotubes (CNT) were prepared by a modified chemical vapor deposition (CVD) method. The synthesized carbon materials were treated with acidic and basic solutions in order to introduce certain surface functional groups, mainly containing oxygen (OCNT) or amine (ACNT) species. These modified CNTs (OCNT and ACNT) as well as the originally prepared CNT were reacted with a non-ionic Fe complex, Iron (II) Phthalocyanine, and three composites were obtained. The amount of metal complex introduced in each case and the interaction between the complex and the CNT materials were studied with the aid of various characterization techniques such as TGA, XRD, and XPS. The results obtained in these experiments all indicated that the interaction between the complex and the CNT was greatly affected by the functionalization of the latter.
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http://dx.doi.org/10.3390/ma14154067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8347569PMC
July 2021

Using Monoclonal Antibody Therapies for Multiple Sclerosis: A Review.

Biologics 2021 30;15:255-263. Epub 2021 Jun 30.

Department of Neurology, Mayo Clinic, Scottsdale, AZ, USA.

Monoclonal antibody therapies have secured an important role in the therapeutic landscape for the treatment of both relapsing and progressive forms of multiple sclerosis due to their potent efficacy, convenient dosing schedules, and well-defined side effect profiles. Each therapy has unique risks and benefits associated with its specific mechanism of action which ultimately guides clinical decision-making for individual patients. This review will summarize the mechanisms of action, evidence leading to their approval, and clinically relevant considerations for each of the current monoclonal antibody therapies approved for the treatment of multiple sclerosis.
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http://dx.doi.org/10.2147/BTT.S267273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255409PMC
June 2021

Routine preoperative resting echocardiography does not predict adverse cardiopulmonary events after bariatric surgery.

Surg Obes Relat Dis 2021 Jun 23;17(6):1133-1137. Epub 2021 Jan 23.

Department of Surgery, University of California-San Francisco, San Francisco, California. Electronic address:

Background: A routine resting echocardiography has been suggested as a means to assess cardiac functioning and predict adverse cardiopulmonary events after bariatric surgery.

Objectives: To describe the findings of routine resting echocardiographs in bariatric surgical candidates over a 3-year period and correlate them with observed adverse cardiopulmonary outcomes.

Setting: Tertiary-care university-based referral hospital.

Methods: We retrospectively reviewed 422 consecutive patients who underwent a laparoscopic sleeve gastrectomy or laparoscopic gastric bypass at our center over 3 years, of whom 321 (76%) received a routine resting preoperative echocardiogram. Abnormal preoperative echocardiogram findings and patient characteristics were recorded. The primary outcome measure was the number of adverse cardiopulmonary events within 30 days of surgery, a composite measure defined as any instance of myocardial infarction, sustained hypotension, stroke, new-onset arrhythmia, heart failure, intensive care admission for cardiopulmonary monitoring, or cardiac arrest.

Results: Routine screening preoperative echocardiograms revealed left ventricular (LV) systolic dysfunction in 7 patients (2%), LV diastolic dysfunction in 71 patients (22%), LV hypertrophy in 73 patients (23%), wall motion abnormalities in 4 patients (1%), pulmonary hypertension in 47 patients (15%), left atrial enlargement in 45 patients (14%), and LV enlargement in 6 patients (1%). Adverse cardiopulmonary events occurred in only 4 patients, all of whom had a history of coronary revascularization, and 3 of whom had a prior myocardial infarction. No finding on the routine preoperative echocardiograms was associated with adverse cardiopulmonary events.

Conclusion: A routine resting preoperative echocardiography added little to the cardiopulmonary risk stratification of patients who underwent bariatric surgery. High-risk patients were identifiable based on their medical history, particularly those with a known history of coronary artery disease and coronary revascularization.
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http://dx.doi.org/10.1016/j.soard.2021.01.021DOI Listing
June 2021

Preventing Recurrence in Clean and Contaminated Hernias Using Biologic Versus Synthetic Mesh in Ventral Hernia Repair: The PRICE Randomized Clinical Trial.

Ann Surg 2021 04;273(4):648-655

Department of Surgery, University of California, San Francisco, CA.

Objective: The aim of this study was to evaluate which mesh type yields lower recurrence and complication rates after ventral hernia repair.

Summary Background Data: More than 400,000 ventral hernia repairs are performed annually in the United States. Although the most effective method for repairing ventral hernias involves using mesh, whether to use biologic mesh versus synthetic mesh is controversial.

Methods: Single-blind, randomized, controlled, pragmatic clinical trial conducted from March 2014 through October 2018; 165 patients enrolled with an average follow up of 26 months. Patients were randomized 1:1 to have their ventral hernias repaired using either a biologic (porcine) or synthetic (polypropylene) mesh. The primary study outcome measure was hernia recurrence at 2 years.

Results: A total of 165 patients (68 men), mean age 55 years, were included in the study with a mean follow-up of 26 months. An intention-to-treat analysis noted that hernias recurred in 25 patients (39.7%) assigned to biologic mesh and in 14 patients (21.9%) assigned to synthetic mesh (P = 0.035) at 2 years. Subgroup analysis identified an increased rate of hernia recurrence in the biologic versus the synthetic mesh group under contaminated wound conditions (50.0% vs 5.9%; P for interaction = 0.041). Postoperative complication rates were similar for the 2 mesh types.

Conclusions: The risk of hernia recurrence was significantly higher for patients undergoing ventral hernia repair with biologic mesh compared to synthetic mesh, with similar rates of postoperative complications. These data indicate that the use of synthetic mesh over biologic mesh to repair ventral hernias is effective and can be endorsed, including under contaminated wound conditions.

Trial Registration: ClinicalTrials.gov Identifier: NCT02041494.
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http://dx.doi.org/10.1097/SLA.0000000000004336DOI Listing
April 2021

Interleukin-6 inhibition with tocilizumab for relapsing MOG-IgG associated disorder (MOGAD): A case-series and review.

Mult Scler Relat Disord 2021 Feb 16;48:102696. Epub 2020 Dec 16.

Departments of Neurology, Mayo Clinic, Scottsdale, AZ, United States.

Background: Myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG) associated disorder (MOGAD) is a CNS demyelinating disease distinct from neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis. Some patients with MOGAD exhibit a highly-relapsing and steroid-dependent disease course for which optimal treatment is unknown. Interleukin-6 (IL-6) plays an important pathobiologic role in NMOSD with aquaporin-4 antibodies and preliminary data suggest similar mechanisms of CNS damage may occur in MOGAD.

Objective: To summarize our experience with and all current literature on the use of tocilizumab, an IL-6 inhibitor, for highly-relapsing MOGAD along with the underlying immunopathologic rationale.

Methods: This is a single-center report from a U.S. military tertiary referral hospital of all patients with clinically, radiographically, and serologically confirmed MOGAD who were treated with tocilizumab compiled with data from five other case series/reports from tertiary referral centers. The main outcomes of interest were reduction in annualized relapse rate and required dose of oral prednisone for symptomatic management.

Results: Ten total patients with relapsing MOGAD who were treated with intravenous or subcutaneous tocilizumab were identified. At our institution, a 20 year-old female with a 9-year history of highly-relapsing and steroid dependent MOGAD was treated with tocilizumab. In 28 months of follow up, she had no clinical relapses and was able to discontinue corticosteroids. Another 35 year-old female at our institution with a 10-year history of highly-relapsing and steroid dependent MOGAD was treated with tocilizumab for 6 months. Tocilizumab therapy was associated with relapse freedom, resolution of eye pain, and ability to discontinue corticosteroids. When compiled with data from all other case reports of relapsing MOGAD treated with tocilizumab, there have been zero clinical or radiographic relapses in 10 patients over an average treatment duration of 28.6 months.

Conclusions: Tocilizumab is an IL-6 inhibitor that may be a promising therapeutic option for patients with relapsing MOGAD that has not responded to other immunotherapies. Our results support a key role for IL-6-related mechanisms in MOGAD disease activity. Its safety and tolerability profile, both in our own experience and based on its use for other FDA approved conditions, may even justify its use a first line therapy in select patients. Further research is needed to establish the safety and efficacy of IL-6 inhibition in MOGAD.
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http://dx.doi.org/10.1016/j.msard.2020.102696DOI Listing
February 2021

The Application, Challenges, and Advancement Toward Regulatory Acceptance of Digital Toxicologic Pathology: Results of the 7th ESTP International Expert Workshop (September 20-21, 2019).

Toxicol Pathol 2021 06 10;49(4):720-737. Epub 2020 Dec 10.

572272Department of Histopathology, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom.

With advancements in whole slide imaging technology and improved understanding of the features of pathologist workstations required for digital slide evaluation, many institutions are investigating broad digital pathology adoption. The benefits of digital pathology evaluation include remote access to study or diagnostic case materials and integration of analysis and reporting tools. Diagnosis based on whole slide images is established in human medical pathology, and the use of digital pathology in toxicologic pathology is increasing. However, there has not been broad adoption in toxicologic pathology, particularly in the context of regulatory studies, due to lack of precedence. To address this topic, as well as practical aspects, the European Society of Toxicologic Pathology coordinated an expert international workshop to assess current applications and challenges and outline a set of minimal requirements needed to gain future regulatory acceptance for the use of digital toxicologic pathology workflows in research and development, so that toxicologic pathologists can benefit from digital slide technology.
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http://dx.doi.org/10.1177/0192623320975841DOI Listing
June 2021

An Australian, single-centre study of surgical management outcomes for early-stage cervical cancer.

Aust N Z J Obstet Gynaecol 2021 02 27;61(1):123-127. Epub 2020 Jul 27.

Lifehouse Gynaecological Oncology Group, Chris O'Brien Lifehouse, Sydney, NSW, Australia.

Background: The Laparoscopic Approach to Cervical Cancer (LACC) trial is the first phase III randomised, multicentred trial to compare oncologic outcomes associated with open radical hysterectomy vs minimally invasive surgery (MIS) for treatment of early cervical cancer.

Aim: To evaluate our surgical experience in patients with early cervical cancer.

Methods And Materials: The Lifehouse Gynaecologic Oncology database was queried based upon the eligibility criteria of the LACC study and included all FIGO 2009 stage (1A1 with lymph vascular space invasion, 1A2, 1B1) cervical cancer women from 2008-2018. Patients were also included in our study if they had abdominal radical trachelectomy (ART), laparoscopic radical hysterectomy (TLRH) and robotic radical trachelectomy (RRT).

Results: Forty-six women were identified with four exclusions. Thirty-seven women had stage 1B1 disease, 24 had a squamous cell carcinoma, 15 had an adenocarcinoma and three had an adenosquamous carcinoma of the cervix. Of the 42 eligible patients, 32 underwent an open abdominal approach (26 total abdominal radical hysterectomy (TARH), six ART) and ten a MIS approach (nine TLRH and one RRT) with a mean follow-up of 4.8 years. All 42 women had a pelvic lymph node dissection, eight women had nodal metastases and 16 patients received adjuvant chemoradiation. Two of the nine women in the laparoscopic radical hysterectomy group had a recurrence. Both had adenocarcinoma, stage 1B1 disease. There were no recurrences in the TARH group or radical trachelectomy groups.

Conclusion: Our data, albeit limited in number, have reflected the results of the LACC trial that MIS was associated with a lower disease-free survival than open radical hysterectomy.
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http://dx.doi.org/10.1111/ajo.13219DOI Listing
February 2021

Haemolymphatic cancer among children in Sardinia, Italy: 1974-2003 incidence.

BMJ Open 2020 11 3;10(11):e037163. Epub 2020 Nov 3.

Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.

Objectives: To explore the time trend and geographical distribution of childhood leukaemia incidence over the territory of the Italian region of Sardinia.

Setting: All hospitals departments, diagnostic centres and social security agencies in Sardinia were regularly screened in 1974-2003 to identify, register and review the diagnoses of incident cases of haematological malignancies (HM).

Participants: The whole child population aged 0-14 resident in Sardinia.

Primary And Secondary Outcome Measures: Incidence and time trend of childhood HM and childhood acute lymphoblastic leukaemia (ALL) over the study period, and use of Bayesian methods to plot the probability of areas with excess incidence on the regional map.

Results: Overall, 675 HM cases, including 378 ALL cases, occurred among children aged 0-14 years resident in Sardinia in 1974-2003, with an incidence rate of 6.97×10 (95% CI 6.47 to 7.51) and 3.85×10 (95% CI 3.48 to 4.26), respectively. Incidence of HM and ALL showed an upward trend along the study period especially among females. Three communes out of the 356 existing in 1974, namely Ittiri, Villa San Pietro and Carbonia, stand out as areas with excess incidence of HM and ALL in particular and another, Carloforte, for ALL only.

Conclusions: Our results might serve as convincing arguments for extending the coverage of routine cancer registration over the whole Sardinian population, while prompting further research on the genetic and environmental determinants in the areas at risk.
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http://dx.doi.org/10.1136/bmjopen-2020-037163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7640504PMC
November 2020

Assessment of current follow-up for complete molar pregnancies: A single centre review.

Aust N Z J Obstet Gynaecol 2021 04 8;61(2):213-216. Epub 2020 Oct 8.

Department of Gynaecology Oncology, Chris O'Brien Lifehouse, Sydney, Australia.

Background: Current guidelines recommend that resolution of a complete molar pregnancy (CMP) can only be confirmed once a negative β-human chorionic gonadotropin (β-hCG) has been maintained for six months following uterine surgical evacuation. However, multiple studies have found that the risk of developing gestational trophoblastic neoplasia (GTN) once a negative β-hCG had been obtained is negligible, which suggests that a shorter follow-up may be reasonable.

Aim: To determine the trend in β-hCG following diagnosis of a CMP and the incidence of GTN, in a single unit.

Materials And Methods: All patients presenting to the tertiary hospital, Royal Prince Alfred Hospital Early Pregnancy Assessment Service (RPAH EPAS), with a histopathological diagnosis of a CMP between 2010 and 2017 were included. Data collected included age, parity, β-hCG at diagnosis, subsequent β-hCG levels, incidence of GTN and treatment required.

Results: Sixty-seven patients were diagnosed with CMP between January 2010 and July 2017 through RPAH EPAS. The mean age of women diagnosed with a CMP was 33 years. None of the 40 patients who spontaneously achieved a negative β-hCG and completed their six months follow-up had a subsequent rise in β-hCG. The median number of days from surgical evacuation to normalisation of β-hCG was 55.5 days. Sixteen out of 67 patients who had a CMP required further management for persistent GTN. None of these patients achieved a negative β-hCG prior to further management.

Conclusions: Consideration could be made to decreasing the period of β-hCG monitoring for women who achieve a spontaneous negative β-hCG following surgical evacuation of a CMP.
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http://dx.doi.org/10.1111/ajo.13258DOI Listing
April 2021

Follow-up after treatment of high-grade cervical dysplasia: The utility of six-month colposcopy and cytology and routine 12-month colposcopy.

Aust N Z J Obstet Gynaecol 2020 12 15;60(6):959-964. Epub 2020 Sep 15.

Gynaecological Oncology, Chris O'Brien Lifehouse, Sydney, New South Wales, Australia.

Background: Australian Cervical Screening Program guidelines no longer recommend colposcopy and cytology at six months following treatment of cervical intraepithelial neoplasia (CIN2/3) and a co-test of cure can be performed at 12 months without colposcopy.

Aims: To determine the usefulness of six-month colposcopy and cytology and routine colposcopy with co-testing at 12 months in detecting persistent or recurrent disease in patients treated for CIN2/3.

Materials And Methods: We conducted a review of all patients with histologically proven CIN2/3 who underwent a cervical excisional procedure between March 2012 and March 2017 in one specialised centre.

Results: We examined 1215 cases and 750 remained after exclusions for analysis. At six months (722 cases, 96.2%) seven of 42 (16.7%) patients with high-grade cytology had a high-grade colposcopy and 24 of 42 (57.1%) had a normal colposcopy. Persistent CIN2/3 was diagnosed in 12 cases (1.7%) and only 1/3 had a high-grade colposcopy. Cytology was more useful than colposcopy in detecting persistent disease. At 12 months (638 cases, 85%) routine colposcopy at the time of co-testing had a high false positive rate with all high-grade changes negative on biopsy and co-test. Recurrent CIN2/3 was diagnosed in five cases, and four had normal colposcopy at co-testing.

Conclusions: There may be a delay in detection of persistent/recurrent CIN2/3 in a small number of cases without six-month colposcopy and cytology; however, it is not likely to negatively impact overall clinical outcome. Co-testing at 12 months following treatment of CIN2/3 without colposcopy is safe and routine colposcopy at collection of the co-test can be omitted.
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http://dx.doi.org/10.1111/ajo.13248DOI Listing
December 2020

Upper Gastrointestinal Endoscopy in an Academic General Surgical Program: Implications for Acute Care Surgeons.

Surg Innov 2020 Dec 7;27(6):669-674. Epub 2020 Sep 7.

Department of Surgery, 8785University of California San Francisco, San Francisco, CA, USA.

Esophagogastroduodenoscopy (EGD) is an important tool in the evolving specialty of acute care surgery (ACS). Understanding the types of nonelective EGDs performed by ACS groups is important for the development of ACS programs and the training of future general surgeons. We conducted a retrospective review of all EGDs performed by ACS surgeons at a single urban academic center over a 5-year period (January 2013-December 2018). A total of 495 EGDs were performed, of which 129 (26%) were urgent, nonelective procedures. Patients who underwent urgent EGD were younger than those who underwent elective procedures (median 55 vs 60 years, = .03), had higher American Society of Anesthesiologists (ASA) classes (median ASA 3 vs 2, = .0002), and longer hospital stays (median 5 days vs 0 days, < .0001). The most common indications for urgent endoscopies were the management of leak, dysphagia, or stenosis in patients with a history of foregut surgery, followed by the management of esophageal perforation. The success rate of endoscopic therapy was high (median 88%, interquartile range (IQR) 78-89%). However, some patients required multiple interventions (median 1, IQR 1-3), and patients treated for leaks were less likely to be successfully treated with endoscopic therapy alone than patients treated for other indications (success rate 65% vs 88%, = .003). Our experience suggests that EGD has an important role in current ACS practice and that endoscopic management is safe and effective in a range of urgent surgical scenarios. Future ACS surgeons should be facile with endoscopic techniques.
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http://dx.doi.org/10.1177/1553350620957802DOI Listing
December 2020

Robotic versus laparoscopic hysterectomy in morbidly obese women for endometrial cancer.

J Robot Surg 2021 Jun 31;15(3):483-487. Epub 2020 Jul 31.

Chris O'Brien Lifehouse, Sydney, Australia.

Surgery is the mainstay treatment for endometrial cancer and complex atypical endometrial hyperplasia. These conditions are more common in the obese women and as such these patients pose additional risks and challenges to surgery. Laparoscopic hysterectomy (LH) is preferred over open surgery in obese patients as it reduces surgical morbidity. However, more recently, robotic-assisted hysterectomy (RH) has been used in morbidly obese patients to overcome the limitations of conventional laparoscopy. To compare the surgical outcomes of morbidly obese patients undergoing LH or RH for endometrial cancer or complex atypical hyperplasia. A retrospective analysis of morbidly obese patients (BMI > 40 kg/m) who underwent LH or RH for endometrial cancer or complex atypical hyperplasia at the Chris O'Brien Lifehouse Gynaecological Oncology Unit from 2015 to 2019 was performed. Data was collected from the prospectively maintained gynaecology oncology database and descriptive analysis was performed. 33 (51.6%) underwent LH and 31 (48.4%) had RH. More LHs were performed 2015-2017 period, whereas there were more RHs performed in 2018-2019 period (p = 0.01). The difference between theatre time use and operating time for LH surgery compared to RH was significantly shorter (45.7 for LH versus 61.9 min for RH, p = 0.009). RH was performed more commonly when BMI was > 50 kg/m (p = 0.02). There has been an increase in the use of RH in morbidly obese patients, particularly for women with a BMI > 50 kg/m.
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http://dx.doi.org/10.1007/s11701-020-01133-zDOI Listing
June 2021

An evaluation of dimethyl fumarate for the treatment of relapsing remitting multiple sclerosis.

Expert Opin Pharmacother 2020 Aug 16;21(12):1399-1405. Epub 2020 Jun 16.

Department of Neurology, Mayo Clinic Arizona, Mayo Foundation for Medical Education and Research , Scottsdale, AZ, USA.

Introduction: In recent years there has been a dramatic rise in available disease-modifying therapies for the treatment of relapsing multiple sclerosis (MS). Dimethyl fumarate (DMF) is an oral drug approved by the FDA for relapsing MS with unique immunomodulatory and cytoprotective effects.

Areas Covered: Herein, the authors provide the reader with a review of the literature obtained via a PubMed database search and provide their expert opinion on the use of DMF in clinical practice. The article details DMF's mechanism of action, long-term data on efficacy, tolerability and safety.

Expert Opinion: Since approval, growing experience with DMF in clinical practice demonstrates a combination of efficacy, ease of administration along with an acceptable safety profile. The authors believe that DMF is a valuable long-term treatment option in patients with relapsing MS. However, long-term follow up studies are needed to provide further data on progressive multifocal leukoencephalopathy (PML) risk stratification for MS patients on treatment with DMF. Indeed, despite the strong association with lymphopenia, not all patients with DMF associated PML experienced prolonged overall lymphopenia, suggesting that additional predictive metrics are still needed.
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http://dx.doi.org/10.1080/14656566.2020.1763304DOI Listing
August 2020

Ampullary stenosis and choledocholithiasis post Roux-En-Y gastric bypass: challenges of biliary access and intervention.

HPB (Oxford) 2020 10 24;22(10):1496-1503. Epub 2020 Apr 24.

University of California San Francisco, Department of Surgery, 513 Parnassus Avenue S-321, San Francisco, CA, 94143-0470, United States; San Francisco Veterans Affairs Medical Center, Department of Surgery, 4150 Clement Street, Box 112, San Francisco, CA, 94121, United States. Electronic address:

Background: Ampullary stenosis following Roux-en-Y gastric bypass (RYGB) is increasingly encountered. We describe cases of biliary obstruction from ampullary stenosis and choledocholithiasis to illustrate the associated diagnostic and interventional challenges with this condition.

Methods: We reviewed medical records of patients with prior RYGB who underwent a biliary access procedure or surgery for non-malignant disease from January 2012-December 2018.

Results: We identified 15 patients (4 male, 11 female; mean age 53.7 years) who had RYGB on average 11.7 years (range 1-32) years before diagnosis of biliary obstruction. Fourteen patients reported abdominal pain, 5 had nausea/emesis, 12 had elevated liver function tests, and 6 had ascending cholangitis. Mean common bile duct (CBD) diameter at presentation was 16.9 mm (range 4.0-25.0 mm). Operations included 3 transduodenal ampullectomies (2 with biliary bypass), 2 CBD explorations with stone extraction, 1 laparoscopic cholecystectomy alone, 1 Whipple procedure, 1 balloon enteroscopy with sphincterotomy, and 7 transgastric endoscopic retrograde cholangiopancreatography. All ampulla pathology was benign in patients who underwent resection. At follow-up (mean 15.4 months; range 0.23-44.5 months), 12/15 (80%) reported symptom resolution or improvement.

Discussion: Ampullary stenosis after RYGB presents challenges for diagnostic evaluation and intervention, often requiring multi-disciplinary expertise. The underlying pathology remains to be elucidated.
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http://dx.doi.org/10.1016/j.hpb.2020.02.004DOI Listing
October 2020

Transcriptome-wide association study of breast cancer risk by estrogen-receptor status.

Genet Epidemiol 2020 07 1;44(5):442-468. Epub 2020 Mar 1.

Department of Radiation Oncology, Hannover Medical School, Hannover, Germany.

Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta-analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER-). We further compared associations with ER+ and ER- subtypes, using a case-only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER- breast cancer. We further identified 30 TWAS-significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast-cancer gene in three of six regions harboring multiple TWAS-significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER- breast cancer.
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http://dx.doi.org/10.1002/gepi.22288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987299PMC
July 2020

The effect of laparoscopic salpingectomy for ectopic pregnancy on ovarian reserve.

Aust N Z J Obstet Gynaecol 2020 04 17;60(2):278-283. Epub 2020 Feb 17.

School of Women's and Children's Health, UNSW, Sydney, New South Wales, Australia.

Background: Salpingectomy may damage ovarian reserve by direct vascular interruption to the ovary or thermal vascular injury from electrosurgery. It is plausible that this risk may increase in the context of salpingectomy conducted for ectopic pregnancy due to the distension of the fallopian tube and vascular changes associated with pregnancy.

Aim: To report anti-Müllerian hormone (AMH) concentrations before and after laparoscopic salpingectomy for ectopic pregnancy as an indicator of change in ovarian reserve.

Materials And Methods: Women aged 18-44 years scheduled for salpingectomy for tubal ectopic pregnancy were prospectively recruited. Serum AMH concentrations were measured immediately prior to surgery, then repeated four months post-operatively. In all cases, salpingectomy was conducted laparoscopically using bipolar electrosurgery and mechanical scissors. A group of women scheduled for uterine curettage for first trimester miscarriage was recruited to ensure any observed change in AMH concentration in the women undergoing salpingectomy was secondary to surgery, rather than an effect of pregnancy.

Results: Paired pre- and post-operative serum AMH concentrations were obtained from 32 women with tubal ectopic pregnancy. The mean age of the women was 33.6 ± 4.6 years. There was no significant difference in the median pre- and post-operative AMH concentrations (13.00 pmol/L (range 5-67 pmol/L) vs 15.25 pmol/L (range 3-96 pmol/L), P = 0.575). Median AMH concentrations also remained stable in women experiencing a first trimester miscarriage (10.40 pmol/L (range 3.9-37.8 pmol/L) vs 13.67 pmol/L (range 2.8-30.5 pmol/L), P = 0.185).

Conclusion: Laparoscopic salpingectomy using electrosurgery and mechanical scissors does not damage ovarian reserve. AMH concentrations do not fluctuate from baseline in the first trimester of pregnancy.
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http://dx.doi.org/10.1111/ajo.13129DOI Listing
April 2020

Increases in PYY and uncoupling of bone turnover are associated with loss of bone mass after gastric bypass surgery.

Bone 2020 02 2;131:115115. Epub 2019 Nov 2.

Departments of Medicine, University of California, San Francisco, San Francisco, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, USA; Endocrine Research Unit, San Francisco VA Health Care System, San Francisco, USA.

Context: The gut hormones peptide YY (PYY) and ghrelin mediate in part the metabolic benefits of Roux-en-Y gastric bypass (RYGB) surgery. However, preclinical data suggest these hormones also affect the skeleton and could contribute to postoperative bone loss.

Objective: We investigated whether changes in fasting serum total PYY and ghrelin were associated with bone turnover marker levels and loss of bone mineral density (BMD) after RYGB.

Design, Setting, Participants: Prospective cohort of adults undergoing RYGB (n=44) at San Francisco academic hospitals.

Main Outcome Measures: We analyzed 6-month changes in PYY, ghrelin, bone turnover markers, and BMD by dual-energy x-ray absorptiometry (DXA) and quantitative computed tomography (QCT). We calculated the uncoupling index (UI), reflecting the relative balance of bone resorption and formation.

Results: Postoperatively, there was a trend for an increase in PYY (+25pg/mL, p=0.07) and a significant increase in ghrelin (+192pg/mL, p<0.01). PYY changes negatively correlated with changes in spine BMD by QCT (r=-0.36, p=0.02) and bone formation marker P1NP (r=-0.30, p=0.05). Relationships were significant after adjustments for age, sex, and weight loss. No consistent relationships were found between ghrelin and skeletal outcomes. Mean 6-month UI was -3.3; UI correlated with spine BMD loss by QCT (r=0.40, p=0.01).

Conclusions: Postoperative PYY increases were associated with attenuated increases in P1NP and greater declines in spine BMD by QCT. Uncoupling of bone turnover correlated with BMD loss. These findings suggest a role for PYY in loss of bone mass after RYGB and highlight the relationship between intestinal and skeletal metabolism.
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http://dx.doi.org/10.1016/j.bone.2019.115115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930344PMC
February 2020

An unusual cause of massive GI hemorrhage in an adult.

Gastrointest Endosc 2019 11 17;90(5):855-856. Epub 2019 Jun 17.

Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.

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http://dx.doi.org/10.1016/j.gie.2019.06.011DOI Listing
November 2019

Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers.

Br J Cancer 2019 07 19;121(2):180-192. Epub 2019 Jun 19.

Department of Gynaecological Oncology, Chris O'Brien Lifehouse and The University of Sydney, Camperdown, NSW, Australia.

Background: Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown.

Methods: We applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants. Associations were assessed using weighted Cox models.

Results: Observed height was not associated with ovarian cancer risk (hazard ratio [HR]: 1.07 per 10-cm increase in height, 95% confidence interval [CI]: 0.94-1.23). Height-GS showed similar results (HR = 1.02, 95% CI: 0.85-1.23). Higher BMI was significantly associated with increased risk in premenopausal women with HR = 1.25 (95% CI: 1.06-1.48) and HR = 1.59 (95% CI: 1.08-2.33) per 5-kg/m increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (P < 0.05).

Conclusion: Our observation of a positive association between BMI and ovarian cancer risk in premenopausal BRCA1/2 mutation carriers is consistent with findings in the general population.
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http://dx.doi.org/10.1038/s41416-019-0492-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6738050PMC
July 2019

Safety of laparoscopy in cervical cancer.

Authors:
Jonathan Carter

Aust N Z J Obstet Gynaecol 2019 06;59(3):E9

Gynaecologic Oncology, The University of Sydney, Sydney, Australia.

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http://dx.doi.org/10.1111/ajo.12934DOI Listing
June 2019

Changes in mammographic density following bariatric surgery.

Surg Obes Relat Dis 2019 Jun 23;15(6):964-968. Epub 2019 Mar 23.

Department of Surgery, University of California, San Francisco, San Francisco, CA.

Background: Obesity and high breast density both increase breast cancer risk but paradoxically are inversely related. Bariatric surgery decreases breast cancer risk, but its impact on mammographic breast density is not well understood.

Objectives: We investigated how mammographic density changes after bariatric surgery and whether this change is related to weight loss.

Setting: University of California, San Francisco Medical Center.

Methods: We reviewed records from 349 prospectively collected patients who underwent bariatric surgery between 2013 and 2015 and identified 42 women with pre- and postoperative screening mammograms within 1.5 years of surgery. We recorded body mass index (BMI), height and Breast Imaging Reporting and Data System density and calculated BMI loss and total weight loss. Data were analyzed in Stata 14.2.

Results: Average age was 54.2 years, mean preoperative BMI was 43.8 kg/m, mean BMI lost was 30.9%, and total weight loss was 31.1% at 1.3 years. Over one-third had a change in mammographic breast density, which increased 93.3% of the time (P < .001). Amount of weight loss was not associated with a density change. Patients with the lowest mammographic density preoperatively were most likely to have a density change (P = .02).

Conclusions: Most women with a mammographic change had an increase in breast density, despite bariatric surgery being associated with reduced breast cancer risk. Baseline breast density was associated with a density change, but amount of weight loss was not. These findings suggest the metabolic effects of bariatric surgery have an effect on breast parenchyma independent of absolute BMI reduction or weight loss.
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http://dx.doi.org/10.1016/j.soard.2019.03.037DOI Listing
June 2019

Safety of concomitant cholecystectomy with laparoscopic sleeve gastrectomy and gastric bypass: a MBSAQIP analysis.

Surg Obes Relat Dis 2019 Jun 20;15(6):864-870. Epub 2019 Mar 20.

Department of Surgery, University of California, San Francisco, California.

Background: Gallstone disease occurs more commonly in the obese population and is often diagnosed during the preoperative evaluation for bariatric surgery.

Objectives: This study analyzed outcomes of laparoscopic gastric bypass (LGB) and laparoscopic sleeve gastrectomy (SG), with and without cholecystectomy (LC), using data from the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program.

Setting: Patients reported to Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program participating centers in the United States and Canada in 2015.

Methods: All cases of LGB and SG, with and without LC, were analyzed. A 1:1 propensity-matched cohort was created for both SG and LGB, with and without concomitant LC. Multivariate logistic regression stratified by procedure was used to identify predictors of major complications after SG and LGB, using concomitant LC as a predictor. We also constructed a model for surgical site infections (SSIs) for SG group.

Results: Of 98,292 sleeve operations, 2046 (2%) had concomitant LC. Of 44,427 bypass operations, 1426 (3%) had concomitant LC. For the sleeve group, concomitant LC increased operative time by an average of 27 minutes but did not affect length of stay, mortality, or major complications. Concomitant LC was associated with increased SSI (1% versus .4%) and need for reoperation (1.6% versus .7%) in univariate models. After adjusting for other predictors, concomitant LC was associated with increased risk for SSI (odds ratio 2.5, confidence interval 1.0-5.9, P = .04). For the bypass group, concomitant LC increased operative time by an average of 28 minutes to the operation, and postoperative length of stay averaged ∼5 hours longer (2.4 versus 2.2 d, P = .03). Thirty-day complications were similar between the groups. On multivariate analysis, concomitant LC was not a significant risk factor for major complications. Only operative time was an independent factor for major complications.

Conclusions: Concomitant LC with laparoscopic sleeve gastrectomy or gastric bypass did not affect mortality or risk of major complication. For sleeve patients, concomitant LC was associated with a .6% increased risk (.4% to 1.0%) of SSI. Concomitant LC with laparoscopic sleeve gastrectomy or gastric bypass is safe when indicated for gallstone disease.
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http://dx.doi.org/10.1016/j.soard.2019.03.004DOI Listing
June 2019

Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer.

Nat Commun 2019 04 15;10(1):1741. Epub 2019 Apr 15.

Molecular Oncology Laboratory, CIBERONC, Hospital Clinico San Carlos, IdISSC (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos), 28040, Madrid, Spain.

Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.
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http://dx.doi.org/10.1038/s41467-018-08053-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6465407PMC
April 2019

Pathways to a cancer-free future: A protocol for modelled evaluations to maximize the future impact of interventions on cervical cancer in Australia.

Gynecol Oncol 2019 03;152(3):465-471

Cancer Research Division, Cancer Council NSW, Sydney, NSW, Australia; School of Public Health, University of Sydney, NSW, Australia; Prince of Wales Clinical School, University of New South Wales, Australia.

Objective: Australia's HPV vaccination and HPV-based cervical screening programs are changing the landscape in cervical cancer prevention. We aim to identify areas which can make the biggest further impact on cervical cancer burden. This protocol describes the first stage of a program of work called Pathways-Cervix that aims to generate evidence from modelled evaluations of interventions across the cervical cancer spectrum.

Methods: Based on evidence from literature reviews and guidance from a multi-disciplinary Scientific Advisory Committee (SAC), the most relevant evaluations for prevention, diagnosis and treatment were identified.

Results: Priority evaluations agreed by the SAC included: increasing/decreasing and retaining vaccination uptake at the current level; vaccinating older women; increasing screening participation; methods for triaging HPV-positive women; improving the diagnosis of cervical intraepithelial neoplasia (CIN) and cancer; treating cervical abnormalities and cancer; and vaccinating women treated for CIN2/3 to prevent recurrence. Evaluations will be performed using a simulation model, Policy1-Cervix previously used to perform policy evaluations in Australia. Exploratory modelling of interventions using idealised scenarios will initially be conducted in single birth cohorts. If these have a significant impact on findings then evaluations with more realistic assumptions will be conducted. Promising strategies will be investigated further by multi-cohort simulations predicting health outcomes, resource use and cost outcomes.

Conclusions: Pathways-Cervix will assess the relative benefits of strategies and treatment options in a systematic and health economic framework, producing a list of 'best buys' for future decision-making in cervical cancer control.
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http://dx.doi.org/10.1016/j.ygyno.2018.12.019DOI Listing
March 2019

Changes in Lean Mass, Absolute and Relative Muscle Strength, and Physical Performance After Gastric Bypass Surgery.

J Clin Endocrinol Metab 2019 03;104(3):711-720

Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Francisco, San Francisco, California.

Context: Bariatric surgery results in reduced muscle mass as weight is lost, but postoperative changes in muscle strength and performance are incompletely understood.

Objective: To examine changes in body composition, strength, physical activity, and physical performance following Roux-en-Y gastric bypass (RYGB).

Design, Participants, Outcomes: In a prospective cohort of 47 adults (37 women, 10 men) aged 45 ± 12 years (mean ± SD) with body mass index (BMI) 44 ± 8 kg/m2, we measured body composition by dual-energy X-ray absorptiometry, handgrip strength, physical activity, and physical performance (chair stand time, gait speed, 400-m walk time) before and 6 and 12 months after RYGB. Relative strength was calculated as absolute handgrip strength/BMI and as absolute strength/appendicular lean mass (ALM).

Results: Participants experienced substantial 12-month decreases in weight (-37 ± 10 kg or 30% ± 7%), fat mass (-48% ± 12%), and total lean mass (-13% ± 6%). Mean absolute strength declined by 9% ± 17% (P < 0.01). In contrast, relative strength increased by 32% ± 25% (strength/BMI) and 9% ± 20% (strength/ALM) (P < 0.01 for both). There were clinically significant postoperative improvements in all physical performance measures, including mean improvement in gait speed of >0.1 m/s (P < 0.01) and decrease in 400-m walk time of nearly a full minute.

Conclusions: In the setting of dramatic weight loss, lean mass and absolute grip strength declined after RYGB. However, relative muscle strength and physical function improved meaningfully and are thus noteworthy positive outcomes of gastric bypass.
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http://dx.doi.org/10.1210/jc.2018-00952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6339456PMC
March 2019

The spectrum of acute cardiopulmonary events associated with multiple sclerosis exacerbations.

Mult Scler 2019 05 18;25(6):758-765. Epub 2019 Jan 18.

Department of Neurology, Mayo Clinic Arizona, Scottsdale, AZ, USA.

Diverse acute neurological injuries may cause acute cardiopulmonary events including neurogenic pulmonary edema (NPE) and neurogenic stunned myocardium (NSM). The mechanism is probably mediated by sympathetic nervous system activation. Focal central nervous system (CNS) lesions, such as demyelinating lesions in multiple sclerosis (MS), may also cause cardiopulmonary disturbances. We aim to review the acute cardiopulmonary events associated with MS relapses. We performed a literature search using PubMed, and selected case reports of acute cardiac and/or pulmonary events related to MS exacerbations. We grouped these events into three categories: 1) NPE with normal cardiac function; 2) NSM and Takotsubo cardiomyopathy (TTC); 3) coexisting myocardial dysfunction and pulmonary edema. In some cases, cardiac and pulmonary symptoms preceded the onset of neurological symptoms. The majority of cases were associated with acute demyelinating lesions located in the medulla. Acute brainstem MS relapses, with demyelinating lesions affecting the medulla, may cause acute cardiac and pulmonary events presumably secondary to sympathetic hyperstimulation. Specific regions in the medulla that regulate cardiac function, systemic blood pressure and pulmonary hydrostatic pressure seem to be responsible for these events.
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http://dx.doi.org/10.1177/1352458518823482DOI Listing
May 2019
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