Publications by authors named "Samir Patel"

467 Publications

Antimicrobial susceptibility profiles of invasive isolates of anaerobic bacteria from a large Canadian reference laboratory: 2012-2019.

Anaerobe 2021 May 25;70:102386. Epub 2021 May 25.

Department of Laboratory Medicine and Pathobiology, University of Toronto, Medical Sciences Building Room 6231, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada; Public Health Ontario, 661 University Avenue, Suite 1701, Toronto, Ontario, M5G 1M1, Canada. Electronic address:

Anaerobic bacteria can cause severe and life threatening infections. Susceptibility data are relatively limited on anaerobic organisms despite the clinical importance in guiding empiric treatment of infections. To determine antimicrobial susceptibility profiles of clinically significant anaerobic bacteria, isolates obtained from sterile sites submitted to Public Health Ontario Laboratory (2012-2019) were included in this study (N = 5712). Cefoxitin, clindamycin, metronidazole, meropenem, penicillin and piperacillin-tazobactam were tested using the gradient strip method with MICs interpreted based on Clinical and Laboratory Standards Institute guidelines. Bacteroides spp. (N = 958; 16.7%), Clostridium spp. (N = 798; 14.0%), Cutibacterium spp. (N =659; 11.5%) and Actinomyces spp. (N = 551; 7.0%) were the most commonly isolated genera. Bacteroides fragilis isolates were susceptible to cefoxitin (88.4%), clindamycin (68.4%), metronidazole (96.0%), meropenem (99.0%) and piperacillin-tazobactam (98.4%). Other Bacteroides spp. showed reduced susceptibility to several antimicrobials. Clostridium spp. isolates were susceptible to penicillin (69.7%), clindamycin (69.7%) and cefoxitin (76.3%); C. perfringens and C. ramosum showed distinct susceptibility profiles. Susceptibility rates among anaerobes remained relatively unchanged over 8 years with a few exceptions: C. perfringens susceptibility to clindamycin decreased from 91.3% to 60% (p = 0.03); Clostridium spp. susceptibility to penicillin similarly decreased from 82.1% to 65.9% (p = 0.03); Eggerthella spp. susceptibility to piperacillin-tazobactam decreased from 100% to 24.3% (p < 0.001); B. fragilis group susceptibility to cefoxitin decreased from 70.4% to 48.2% (p = 0.05); and Parabacteroides spp. susceptibility to piperacillin-tazobactam decreased from 100% to 25% (p = 0.01). Our findings underscore the need for ongoing surveillance and periodic monitoring of antimicrobial resistance in order to guide empiric therapy.
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http://dx.doi.org/10.1016/j.anaerobe.2021.102386DOI Listing
May 2021

The influence of universal face mask use on endophthalmitis risk after intravitreal anti-VEGF injections during the COVID-19 pandemic.

Ophthalmology 2021 May 18. Epub 2021 May 18.

Objective: Routine use of face masks for patients and physicians during intravitreal anti-vascular endothelial growth factor (VEGF) injections has increased with the emergence of the COVID-19 pandemic. This study evaluates the impact of physician, ancillary staff, and patient face mask use on rates and outcomes of post-injection endophthalmitis.

Design: Retrospective, multicenter, comparative cohort study PARTICIPANTS: Eyes receiving intravitreal anti-VEGF injections from 10/1/2019 to 7/31/2020 at twelve centers from the United States of America.

Intervention: Cases were divided into a "no face mask" group if no face masks were worn by the physician or patient during intravitreal injections or a "universal face mask" group if face masks were worn by the physician, ancillary staff, and patient during intravitreal injections.

Main Outcome Measures: Rate of endophthalmitis, microbial spectrum, and visual acuity.

Results: Of 505,968 intravitreal injections from 110,547 eyes administered, 85 of 294,514 (0.0289%; 1 in 3,464 injections) cases of presumed endophthalmitis occurred in the "no face mask" group, and 45 of 211,454 (0.0213%; 1 in 4,699) cases occurred in the "universal face mask" group (odds ratio [OR], 0.74; 95%CI, 0.51-1.18; p=0.097). In the "no face mask" group, there were 27 cases (0.0092%; 1 in 10,908 injections) of culture-positive endophthalmitis compared to 9 cases (0.004%; 1 in 23,494) in the "universal face mask" group (OR, 0.46; 95%CI, 0.22-0.99; p=0.041). Three cases of oral flora-associated endophthalmitis occurred in the "no face mask" group (0.001%; 1 in 98,171 injections) compared to one (0.0005%; 1 in 211,454) in the "universal face mask" group (p=0.645). Patients presented a mean (range) 4.9 (1-30) days after the causative injection, and mean logMAR visual acuity at endophthalmitis presentation was 2.04 [∼20/2200] for "no face mask" group compared to 1.65 [∼20/900] for the "universal face mask" group (p=0.022), although no difference was observed three months after treatment (p=0.764).

Conclusion: In a large, multicenter, retrospective study, physician and patient face mask use during intravitreal anti-VEGF injections did not alter the risk of presumed acute-onset bacterial endophthalmitis, but there was a reduced rate of culture-positive endophthalmitis. Three months following presentation, there was no difference in visual acuity between the groups.
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http://dx.doi.org/10.1016/j.ophtha.2021.05.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130590PMC
May 2021

Geographic Access Disparities to Clinical Trials in Retinopathy of Prematurity in the United States.

Retina 2021 May 13. Epub 2021 May 13.

Wills Eye Hospital, Mid Atlantic Retina, Thomas Jefferson University, Philadelphia, PA.

Purpose: To identify geographic and socioeconomic variables predictive of residential proximity to retinopathy of prematurity (ROP) clinical trial locations.

Methods: This cross-sectional epidemiological study employed census-tract level data from 3 national public datasets and trial-level data from ClinicalTrials.gov. Socioeconomic predictors of driving distance and time to the nearest ROP clinical trial location were identified. Primary outcomes were time >60 minutes and distance >60 miles traveled to the nearest ROP clinical trial.

Results: Multivariate analysis showed that residents were more likely to travel >60 minutes to the nearest ROP clinical trial if they lived in census tracts that were rural [adjusted odds ratio (aOR) 1.20, (P = 0.0002], had higher percentages of the population living ≤ federal poverty level (4th Quartile vs 1st Quartile, aOR 1.19, P < 0.0001), or had less education (Associates vs. Bachelor's degree, aOR 1.01 , P <0.007). In contrast, counties with higher percentages of births <1500g (aOR 0.88, P = 0.0062) were less likely to travel >60 minutes. Similar variables predicted travel distance.

Conclusions: Although counties with higher incidences of very-low birth weight infants were closer to ROP clinical trial sites, residents living in rural and low-income census tracts had significantly greater travel burdens.
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http://dx.doi.org/10.1097/IAE.0000000000003218DOI Listing
May 2021

Surgical failures after primary scleral buckling for rhegmatogenous retinal detachment: comparison of eyes with and without proliferative vitreoretinopathy.

Retina 2021 May 10. Epub 2021 May 10.

Wills Eye Hospital, Mid Atlantic Retina, Thomas Jefferson University, Philadelphia, PA.

Purpose: To compare proliferative vitreoretinopathy (PVR)-related surgical failure and non-PVR associated failure following scleral buckling (SB) for primary rhegmatogenous retinal detachment (RRD).

Methods: In this single-center, retrospective, consecutive case series, eyes with surgical failure after SB for primary RRD were identified. Eyes with surgical failure were categorized as PVR and non-PVR associated failure, and these groups were compared.

Results: Of 530 SB procedures performed, 69 were surgical failures (13%), of which 27/530 (5%) were due to PVR and 42/530 (8%) were from non-PVR causes. Patients with PVR-associated failure were more likely to be smokers (P<0.001), have a delayed presentation after symptoms (P=0.011), have pre-operative vitreous hemorrhage (P=0.004), and have pre-operative PVR (P=0.002). Multivariate logistic regression models showed the odds of PVR-associated failure were greater in eyes with preoperative vitreous hemorrhage (OR, 8.2; P=0.048), preoperative PVR (OR, 22.7; P=0.023), and among prior smokers (OR, 28.8; P<0.001). Thirty-two of 69 (46%) patients required one additional surgical intervention, and 37/69 (53%) required two or more additional interventions to achieve final reattachment.

Conclusion: PVR-related surgical failure after primary SB was 5%. Risk factors for PVR-associated failure parallel those commonly referenced for pars plan vitrectomy, including smoking history, preoperative vitreous hemorrhage and preoperative PVR.
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http://dx.doi.org/10.1097/IAE.0000000000003214DOI Listing
May 2021

Monitoring the patterns of submission and presence of tick-borne pathogens in Ixodes scapularis collected from humans and companion animals in Ontario, Canada (2011-2017).

Parasit Vectors 2021 May 17;14(1):260. Epub 2021 May 17.

Field Studies, Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada.

Background: The universal nature of the human-companion animal relationship and their shared ticks and tick-borne pathogens offers an opportunity for improving public and veterinary health surveillance. With this in mind, we describe the spatiotemporal trends for blacklegged tick (Ixodes scapularis) submissions from humans and companion animals in Ontario, along with pathogen prevalence.

Methods: We tested tick samples submitted through passive surveillance (2011-2017) from humans and companion animals for Borrelia burgdorferi, Borrelia miyamotoi, Anaplasma phagocytophilum and Babesia microti. We describe pathogen prevalence in ticks from humans and from companion animals and constructed univariable Poisson and negative binomial regression models to explore the spatiotemporal relationship between the rates of tick submissions by host type.

Results: During the study, there were 17,230 blacklegged tick samples submitted from humans and 4375 from companion animals. Tick submission rates from companion animals were higher than expected in several public health units (PHUs) lacking established tick populations, potentially indicating newly emerging populations. Pathogen prevalence in ticks was higher in PHUs where established blacklegged tick populations exist. Borrelia burgdorferi prevalence was higher in ticks collected from humans (maximum likelihood estimate, MLE = 17.5%; 95% confidence interval, CI 16.97-18.09%) than from companion animals (9.9%, 95% CI 9.15-10.78%). There was no difference in pathogen prevalence in ticks by host type for the remaining pathogens, which were found in less than 1% of tested ticks. The most common co-infection B. burgdorferi + B. miyamotoi occurred in 0.11% of blacklegged ticks from humans and animals combined. Borrelia burgdorferi prevalence was higher in unengorged (21.9%, 95% CI 21.12-22.65%) than engorged ticks (10.0%, 95% CI 9.45-10.56%). There were no consistent and significant spatiotemporal relationships detected via regression models between the annual rates of submission of each host type.

Conclusions: While B. burgdorferi has been present in blacklegged ticks in Ontario for several decades, other tick-borne pathogens are also present at low prevalence. Blacklegged tick and pathogen surveillance data can be used to monitor risk in human and companion animal populations, and efforts are under consideration to unite surveillance efforts for the different target populations.
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http://dx.doi.org/10.1186/s13071-021-04750-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127263PMC
May 2021

Stereotactic Radiosurgery for Differentiated Thyroid Cancer Brain Metastases: An International, Multicenter Study.

Thyroid 2021 May 11. Epub 2021 May 11.

Department of Neurosurgery, University of Virginia, Charlottesville, Virginia, USA.

Brain metastases (BM) from differentiated thyroid cancer are rare. Stereotactic radiosurgery (SRS) is commonly used for the treatment of BMs; however, the experience with SRS for thyroid cancer BMs remains limited. The goal of this international, multi-centered study was to evaluate the efficacy and safety of SRS for thyroid cancer BMs. From 10 institutions participating in the International Radiosurgery Research Foundation, we pooled patients with established papillary or follicular thyroid cancer diagnosis who underwent SRS for histologically confirmed or radiologically suspected BMs. We investigated patient overall survival (OS), local tumor control, and adverse radiation events (AREs). We studied 42 (52% men) patients who underwent SRS for 122 papillary (83%) or follicular (17%) thyroid cancer BMs. The mean age at SRS was 59.86 ± 12.69 years. The mean latency from thyroid cancer diagnosis to SRS for BMs was 89.05 ± 105.49 months. The median number of BMs per patient was 2 (range: 1-10 BMs). The median SRS treatment volume was 0.79 cm (range: 0.003-38.18 cm), and the median SRS prescription dose was 20 Gy (range: 8-24 Gy). The median survival after SRS for BMs was 14 months (range: 3-58 months). The OS was significantly shorter in patients harboring ≥2 BMs, when compared with patients with one BM (Log-rank = 5.452,  = 0.02). Two or more BMs (odds ratio [OR] = 3.688; confidence interval [CI]: 1.143-11.904;  = 0.03) and lower Karnofsky performance score at the time of SRS (OR = 0.807; CI: 0.689-0.945;  = 0.008) were associated with shorter OS. During post-SRS imaging follow-up of 25.21 ± 30.49 months, local failure (progression and/or radiation necrosis) of BMs treated with SRS was documented in five (4%) BMs at 7.2 ± 7.3 months after the SRS. At the last imaging follow-up, the majority of patients with available imaging data had stable intracranial disease (33%) or achieved complete (26%) or partial (24%) response. There were no clinical AREs. Post-SRS peritumoral T2/fluid attenuated inversion recovery signal hyperintensity was noted in 7% BMs. The SRS allows durable local control of papillary and follicular thyroid cancer BMs in the vast majority of patients. Higher number of BMs and worse functional status at the time of SRS are associated with shorter OS in patients with thyroid cancer BMs. The SRS is safe and is associated with a low risk of AREs.
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http://dx.doi.org/10.1089/thy.2020.0947DOI Listing
May 2021

Temporal Dynamics and Evolution of SARS-CoV-2 Demonstrate the Necessity of Ongoing Viral Genome Sequencing in Ontario, Canada.

mSphere 2021 05 5;6(3). Epub 2021 May 5.

Division of Microbiology, Kingston Health Sciences Centre, Kingston, Ontario, Canada.

Genome-wide variation in SARS-CoV-2 reveals evolution and transmission dynamics which are critical considerations for disease control and prevention decisions. Here, we review estimates of the genome-wide viral mutation rates, summarize current COVID-19 case load in the province of Ontario, Canada (5 January 2021), and analyze published SARS-CoV-2 genomes from Ontario (collected prior to 24 November 2020) to test for more infectious genetic variants or lineages. The reported mutation rate (∼10 nucleotide [nt] cycle) for SARS-CoV-2 is typical for coronaviruses. Analysis of published SARS-CoV-2 genomes revealed that the G614 spike protein mutation has dominated infections in Ontario and that SARS-CoV-2 lineages present in Ontario have not differed significantly in their rate of spread. These results suggest that the SARS-CoV-2 population circulating in Ontario has not changed significantly to date. However, ongoing genome monitoring is essential for identification of new variants and lineages that may contribute to increased viral transmission.
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http://dx.doi.org/10.1128/mSphere.00011-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103981PMC
May 2021

Projected shifts in loggerhead sea turtle thermal habitat in the Northwest Atlantic Ocean due to climate change.

Sci Rep 2021 Apr 23;11(1):8850. Epub 2021 Apr 23.

Coonamessett Farm Foundation, 277 Hatchville Road, East Falmouth, MA, 02536, USA.

It is well established that sea turtles are vulnerable to atmospheric and oceanographic shifts associated with climate change. However, few studies have formally projected how their seasonal marine habitat may shift in response to warming ocean temperatures. Here we used a high-resolution global climate model and a large satellite tagging dataset to project changes in the future distribution of suitable thermal habitat for loggerheads along the northeastern continental shelf of the United States. Between 2009 and 2018, we deployed 196 satellite tags on loggerheads within the Middle Atlantic Bight (MAB) of the Northwest Atlantic continental shelf region, a seasonal foraging area. Tag location data combined with depth and remotely sensed sea surface temperature (SST) were used to characterize the species' current thermal range in the MAB. The best-fitting model indicated that the habitat envelope for tagged loggerheads consisted of SST ranging from 11.0° to 29.7 °C and depths between 0 and 105.0 m. The calculated core bathythermal range consisted of SSTs between 15.0° and 28.0 °C and depths between 8.0 and 92.0 m, with the highest probability of presence occurred in regions with SST between 17.7° and 25.3 °C and at depths between 26.1 and 74.2 m. This model was then forced by a high-resolution global climate model under a doubling of atmospheric CO to project loggerhead probability of presence over the next 80 years. Our results suggest that loggerhead thermal habitat and seasonal duration will likely increase in northern regions of the NW Atlantic shelf. This change in spatiotemporal range for sea turtles in a region of high anthropogenic use may prompt adjustments to the localized protected species conservation measures.
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http://dx.doi.org/10.1038/s41598-021-88290-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065110PMC
April 2021

Efficacy and Safety of Once-Daily LCP-Tacrolimus Versus Twice-Daily Immediate-Release Tacrolimus in Adult Hispanic Stable Kidney Transplant Recipients: Sub-Group Analysis from a Phase 3 Trial.

Ann Transplant 2021 Apr 16;26:e929535. Epub 2021 Apr 16.

Department of Medicine, Ronald Reagan UCLA Medical Center, Los Angeles, CA, USA.

BACKGROUND The pharmacokinetics and metabolism of tacrolimus, an immunosuppressant commonly used to prevent transplant rejection, can differ in specific subpopulations. This analysis examined treatment outcomes and safety of immediate-release tacrolimus (IR-Tac) and LCP-tacrolimus (LCPT) in stable Hispanic kidney transplant recipients. MATERIAL AND METHODS This was a post hoc analysis of clinical trial data from Hispanic adult stable kidney transplant recipients randomized to remain on IR-Tac or convert from IR-Tac to a reduced dose of LCPT (NCT00817206). Composite treatment failure was evaluated at 12 months. Estimated glomerular filtration rate and tacrolimus trough concentrations were evaluated over 12 months. RESULTS Fifty-five stable (LCPT n=26, IR-Tac n=29) kidney transplant recipients who self-identified as Hispanic or Latino were included in this analysis. Composite treatment failure occurred in 1 patient (4%) who converted to LCPT and 1 (3%) who remained on IR-Tac. The estimated glomerular filtration rate was stable over time and similar in the 2 treatment groups (P=0.08). Tacrolimus trough levels for both groups were similar over time in the 2 treatment groups (P=0.98). Treatment-emergent adverse events were similar in patients who converted to LCPT and in those who remained on IR-Tac. CONCLUSIONS Efficacy and safety were similar in Hispanic kidney transplant recipients who converted from IR-Tac to LCPT and in those remaining on IR-Tac.
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http://dx.doi.org/10.12659/AOT.929535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056872PMC
April 2021

Geographic Access Disparities of Clinical Trials in Neovascular Age-Related Macular Degeneration in the United States.

Am J Ophthalmol 2021 Apr 20;229:160-168. Epub 2021 Apr 20.

From Wills Eye Hospital, Mid Atlantic Retina, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. Electronic address:

To identify geographic and socioeconomic variables predictive of residential proximity to neovascular age-related macular degeneration (nAMD) clinical trial locations.

Design: Retrospective, cross-sectional study.

Methods: Census tract-level data from public datasets and trial-level data from ClinicalTrials.gov were analyzed. We calculated the driving distance (>60 miles) and time (>60 minutes) from the population-weighted US census tract centroid to the nearest clinical trial site.

Results: We identified 42 trials studying nAMD across 829 unique clinical trial sites in the United States. In a multivariable model, driving distance >60 miles had a significant association with rural location (adjusted odds ratio [aOR] 5.54; 95% confidence interval [CI] 3.86-7.96, P < .0001) and with Midwest (aOR 2.30; 95% CI 1.21-4.38, P = .01) and South (aOR 2.43; 95% CI 1.21-4.91, P = .01) as compared to the Northeast region, and with some college or an associate's degree, as compared to a bachelor's degree (aOR 1.02; 95% CI 1.01-1.04, P = .0007, and aOR 1.05; 95% CI 1.00-1.10, P = .04, respectively). Lower odds of traveling >60 miles to the nearest nAMD trial site were associated with census tracts with a higher percentage of blacks (aOR 0.98; 95% CI 0.97-0.99, P < .0001), Hispanics (aOR 0.97; 95% CI 0.95-0.99, P = .002), and Asians (aOR 0.90; 95% CI 0.88-0.93, P < .0001), as compared to whites, and with a lower percentage of the population <200% of the federal poverty level. Similar predictors were found in time traveled >60 minutes.

Conclusions: There are geographic access disparities of clinical trial sites for nAMD in the United States.
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http://dx.doi.org/10.1016/j.ajo.2021.04.001DOI Listing
April 2021

Supportive care for toxicities in children undergoing radiation therapy.

Pediatr Blood Cancer 2021 May;68 Suppl 2:e28597

Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.

Radiation therapy (RT) is an integral part of the management of many pediatric tumors; however, it is associated with both acute and permanent adverse events that can significantly impact a child's quality of life, lead to treatment delays, and potentially affect outcomes of cancer therapy. Prevention, early detection, and optimal management of these adverse effects will help reduce their impact on the patients' quality of life and overall well-being. Unfortunately, there has not been a coordinated effort to study the etiology, evaluate risk factors, and explore novel treatments for these conditions. Studies of supportive care for children undergoing RT are often small and uncontrolled. This review will focus on the impact of irradiation on the different organ systems and their current management. Further studies are required to improve our understanding of the contributing factors and explore novel treatment options for these adverse effects and to enable children and their families to better cope with some of the unavoidable toxicities following multimodality therapy.
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http://dx.doi.org/10.1002/pbc.28597DOI Listing
May 2021

Rare tumors: Retinoblastoma, nasopharyngeal cancer, and adrenocorticoid tumors.

Pediatr Blood Cancer 2021 May;68 Suppl 2:e28253

Department of Radiation Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.

The role of surgery, chemotherapy, and radiation therapy for retinoblastoma has evolved considerably over the years with the efficacy of intraarterial chemotherapy and the high incidence of secondary malignant neoplasms following radiation therapy. The use of spot scanning intensity-modulated proton therapy may reduce the risk of secondary malignancies. For pediatric nasopharyngeal carcinoma, the current standard of care is induction chemotherapy followed by chemoradiation therapy. For adrenocortical carcinoma, the mainstay of treatment is surgery and chemotherapy. The role of radiation therapy remains to be defined.
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http://dx.doi.org/10.1002/pbc.28253DOI Listing
May 2021

Chemoport Insertion-Less Is More.

Indian J Surg Oncol 2021 Mar 7;12(1):139-145. Epub 2021 Jan 7.

HCG Cancer Hospital, Ahmedabad, India.

Implantable chemoport is a very useful device for long-term venous access for infusion of chemotherapeutic drugs and other agents. There are few studies from resource poor countries reporting complications of chemoport. The aim of the present study is to evaluate the feasibility of chemoport insertion without image guidance and by closed technique without direct visualisation of a major vein (mainly IJV) and to study the complications associated with the procedure. This was a prospective observational study which analysed 263 patients who underwent chemoport insertion. The medical records of these patients were analysed for the patient characteristics, diagnosis, port-related complications, and their management. A total of 263 patients who were harbouring either locoregionally advanced or metastatic tumour requiring either chemotherapy or targeted treatment or both were included in the study. In total, 133 (50.57%) were female patients and 130 were male patients (49.43%). A total of 236 patients (89.73%) underwent port insertion procedures under local anaesthesia. None of the patients had any major intra-operative complications. Postoperatively, 4 patients (1.52%) were found to have port catheter malposition; 3 out of this 4 were corrected under IITV guidance as a second procedure under local anaesthesia only. One patient (0.38%) required formal removal and replacement of port. Four patients (1.52%) developed IJV thrombosis requiring port removal and anti-coagulation. One patient (0.38%) developed thrombus in the right atrium. There were 2 port site infections (0.74%) requiring port removal (SSI cat. 5). Low complication rates of port insertion were observed in the present, large, prospective study. Complication rates may be further reduced by using a well-designed procedure, experienced surgeons, an aseptic environment, ultrasound-guided puncture, and fluoroscopy with contrast media.

Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-020-01265-6.
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http://dx.doi.org/10.1007/s13193-020-01265-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960807PMC
March 2021

Epiretinal Membrane Surgery after Retinal Detachment Repair: Visual Acuity Outcomes and OCT Analysis.

Ophthalmol Retina 2021 Mar 29. Epub 2021 Mar 29.

Wills Eye Hospital, Mid Atlantic Retina, Thomas Jefferson University, Philadelphia, Pennsylvania. Electronic address:

Purpose: To assess visual acuity (VA) outcomes of epiretinal membrane (ERM) surgery following primary rhegmatogenous retinal detachment (RD) repair and to identify OCT features predictive of visual outcomes.

Design: Retrospective, consecutive case series.

Subjects: Eyes undergoing pars plana vitrectomy (PPV) with membrane peel (MP) surgery for ERM following primary RD repair (PPV with or without scleral buckle (SB) and gas tamponade).

Methods: Retrospective chart review from 2015 to 2018. A previously described ERM grading scale was utilized for OCT structural analysis.

Main Outcome Measures: Visual acuity (VA) and change in VA from pre- MP to 6 months and final follow-up. Secondary outcomes included RD and OCT features predictive of VA, as well as RD factors associated with need for subsequent MP surgery.

Results: 53 eyes of 53 patients underwent MP following RD repair. VA improved significantly from logMAR 1.00 ± 0.51 (Snellen 20/200) pre-MP to 0.45 ± 0.41 (20/56) at 6 months and 0.42 ± 0.41 (20/53) at final follow-up, (p<0.001) for each respectively. Macula on eyes had better 6 month [0.29 ± 0.18 (20/39) vs. 0.51 ± 0.46 (20/65), p=0.02] and final VA [0.29 ± 0.14 (20/39) vs. 0.46 ± 0.47 (20/58), p=0.04] after MP surgery. VA improved significantly from pre-MP to 6 months and final follow-up regardless of macula status. MP occurring ≤180 days from RD repair and IS/OS loss were associated with worse pre-MP VA [1.13 ± 0.09 (20/270) vs. 0.82 ± 0.07(20/132), p=0.01 and 1.21 ± 0.07 (20/324) vs. 0.74 ± 0.09 (20/110) p=0.0003, respectively]. IS/OS loss [adjusted means 0.54 ± 0.07 (20/69) vs. 0.25 ± 0.08 (20/36) at final visit, p=0.006] and RD repair with PPV/SB [0.53 ± 0.08 (20/68) vs. 0.31 ±0.07 (20/41) at final visit, p=0.03] were significantly associated with worse VA at both 6 months and final follow-up.

Conclusions: Eyes undergoing MP after RD repair have significant visual acuity gains independent of macula-status at time of RD repair. Pre-operative IS/OS disruption was the OCT feature best predictive of visual acuity.
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http://dx.doi.org/10.1016/j.oret.2021.03.013DOI Listing
March 2021

The Reality of Randomized Controlled Trials for Assessing the Benefit of Proton Therapy: Critically Examining the Intent-to-Treat Principle in the Presence of Insurance Denial.

Adv Radiat Oncol 2021 Mar-Apr;6(2):100635. Epub 2020 Dec 2.

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Purpose: This study hypothesized that insurance denial would lead to bias and loss of statistical power when evaluating the results from an intent-to-treat (ITT), per-protocol, and as-treated analyses using a simulated randomized clinical trial comparing proton therapy to intensity modulated radiation therapy where patients incurred increasing rates of insurance denial.

Methods And Materials: Simulations used a binary endpoint to assess differences between treatment arms after applying ITT, per-protocol, and as-treated analyses. Two scenarios were developed: 1 with clinical success independent of age and another assuming dependence on age. Insurance denial was assumed possible for patients <65 years. All scenarios considered an age distribution with mean ± standard deviation: 55 ± 15 years, rates of insurance denial ranging from 0%-40%, and a sample of N = 300 patients (150 per arm). Clinical success rates were defined as 70% for proton therapy and 50% for intensity modulated radiation therapy. The average treatment effect, bias, and power were compared after applying 5000 simulations.

Results: Increasing rates of insurance denial demonstrated inherent weaknesses among all 3 analytical approaches. With clinical success independent of age, a per-protocol analysis demonstrated the least bias and loss of power. When clinical success was dependent on age, the per-protocol and ITT analyses resulted in a similar trend with respect to bias and loss of power, with both outperforming the as-treated analysis.

Conclusions: Insurance denial leads to misclassification bias in the ITT analysis, a missing data problem in the per-protocol analysis, and covariate imbalance between treatment arms in the as-treated analysis. Moreover, insurance denial forces the critical appraisal of patient features (eg, age) affected by the denial and potentially influencing clinical success. In the presence of insurance denial, our study suggests cautious reporting of ITT and as-treated analyses, and placing primary emphasis on the results of the per-protocol analysis.
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http://dx.doi.org/10.1016/j.adro.2020.100635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940795PMC
December 2020

Phenotypic and Genomic Profiling of Staphylococcus argenteus in Canada and the United States and Recommendations for Clinical Result Reporting.

J Clin Microbiol 2021 May 19;59(6). Epub 2021 May 19.

Public Health Ontario, Toronto, Ontario, Canada

is a newly described species, formerly known as clonal complex 75 (CC75). Here, we describe the largest collection of isolates in North America, highlighting identification challenges. We present phenotypic and genomic characteristics and provide recommendations for clinical reporting. Between 2017 and 2019, 22 isolates of were received at 2 large reference laboratories for identification. Identification with routine methods (biochemical, matrix-assisted laser desorption ionization-time of flight mass spectrometry [MALDI-TOF MS], 16S rRNA gene analysis) proved challenging to confidently distinguish these isolates from Whole-genome sequencing analysis was employed to confirm identifications. Using several different sequence-based analyses, all clinical isolates under investigation were confirmed to be with clear differentiation from Seven of 22 isolates were recovered from sterile sites, 11 from nonsterile sites, and 4 from surveillance screens. While sequence types ST1223/ type XV, ST2198/ type XIV, and ST2793/ type XId were identified among the Canadian isolates, the majority of isolates (73%) belonged to multilocus sequence types (MLST) ST2250/ type XId and exhibited a high degree of homology at the genomic level. Despite this similarity, 5 types were identified among ST2250 isolates, demonstrating some diversity between strains. Several isolates carried , as well as other resistance and virulence determinants (e.g., PVL, TSST-1) commonly associated with Based on our findings, the growing body of literature on , the potential severity of infections, and possible confusion associated with reporting, including use of incorrect breakpoints for susceptibility results, we make recommendations for clinical laboratories regarding this organism.
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http://dx.doi.org/10.1128/JCM.02470-20DOI Listing
May 2021

Clinical Outcomes of the CHIRP Trial: A Phase II Prospective Randomized Trial of Conventionally Fractionated Versus Moderately Hypofractionated Prostate and Pelvic Nodal Radiation Therapy in Patients With High-Risk Prostate Cancer.

Pract Radiat Oncol 2021 Mar 9. Epub 2021 Mar 9.

Division of Radiation Oncology, Cross Cancer Institute, Edmonton, AB, Canada; Department of Oncology, University of Alberta, Edmonton, AB, Canada. Electronic address:

Purpose: Hypofractionated radiation therapy (HFRT) may offer treatment advantages for patients with prostate cancer. However, HFRT may also increase the risk of gastrointestinal (GI) or genitourinary (GU) toxicity compared with conventionally fractionated radiation therapy (CFRT). Several large trials have found that HFRT is well tolerated in mixed risk population studies. Here, we report on a phase II, randomized controlled study conducted to evaluate these endpoints in exclusively high-risk patients with prostate cancer treated with prostate and pelvic nodal radiation.

Methods And Materials: After giving informed consent, patients with high-risk prostate cancer were randomly assigned to prostate plus pelvic nodal radiation therapy with either HFRT (68 Gy in 25 fractions) or CFRT (78 Gy in 39 fractions) and 18 months of androgen suppression therapy. Toxicity was scored using the Common Terminology Criteria for Adverse Events (version 4.0). Biochemical failure was determined by the Phoenix definition. Patients were analyzed on an intention-to-treat basis.

Results: From 2012 to 2018, 111 patients with high-risk prostate cancer were enrolled and 109 patients were treated. The cumulative incidence of grade 2 or higher acute GI toxicity was not significantly different between the arms (HFRT 18.9% vs CFRT 21.8%; P = .812). Similarly, acute GU (HFRT 30.2% vs CFRT 30.9%; P = 1.00), late GI (HFRT 16.0% vs CFRT 10.0%; P = .554), and late GU (HFRT 16.0% vs CFRT 6.0%; P = .200) were not significantly different between the arms. Median follow-up was 38.0 months (4.8-77.8 months). The 3-year biochemical recurrence-free survival was not significantly different between the 2 arms (97.3% for HFRT vs 91.0% for CFRT; P = .606). The 3-year overall survival was 94.8% in the HFRT arm and 100.0% in the CFRT arm (P = .116).

Conclusions: HFRT and CFRT using intensity modulated radiation therapy were both well tolerated for patients with high-risk prostate cancer and resulted in similar 3-year biochemical recurrence-free survival and overall survival.
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http://dx.doi.org/10.1016/j.prro.2021.02.011DOI Listing
March 2021

Quantification of Potential Inequities in Breast Cancer Incidence in New Mexico Through Bayesian Disease Mapping.

Prev Chronic Dis 2021 Mar 11;18:E23. Epub 2021 Mar 11.

Department of Health Sciences Research, Mayo Clinic, Scottsdale, Arizona.

Introduction: The incidence of breast cancer among non-Hispanic American Indian and Alaska Native (AI/AN) women varies across the United States. We applied county-level Bayesian disease mapping to quantify potential inequities in 10-year breast cancer incidence in New Mexico to better inform health equity initiatives among its non-Hispanic at-risk AI/AN population.

Methods: We used data from the Surveillance, Epidemiology, and End Results (SEER) program from 2005 through 2014 to identify new cases of breast cancer in New Mexico's 33 counties. To account for spatial variation, a county-level Area Deprivation Index, and the small area estimation problem inherent in these data, we borrowed strength globally and locally by applying Bayesian disease mapping to the counts of age-adjusted county-level breast cancer incidence. We quantified the disparity effect, as measured by the age-adjusted rate ratio, comparing the incidence of breast cancer between at-risk non-Hispanic AI/AN and non-Hispanic White women and assessed whether the ratio differed among counties.

Results: Accounting for over-dispersion and spatial correlation among the 33 counties and a county-level Area Deprivation Index, the posterior mean of the overall age-adjusted rate ratio was 0.384 (95% credible interval, 0.253--0.546). The age-adjusted rate of breast cancer in non-Hispanic AI/AN women was 0.38 times the corresponding age-adjusted rate for non-Hispanic White women; however, a significant reduction in breast cancer incidence was observed in 16 of the 33 counties.

Conclusion: The application of Bayesian disease mapping to these data provided substantial evidence of an overall disparity in breast cancer incidence between at-risk non-Hispanic AI/AN and non-Hispanic White women in New Mexico, which was more marked than previously reported and limited to certain counties. Targeted statewide and county-level health-equity initiatives may lead to a reduction in these disparities.
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http://dx.doi.org/10.5888/pcd18.200468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986972PMC
March 2021

The Benefits and Harms of Antibiotic Prophylaxis for Urinary Tract Infection in Older Adults.

Clin Infect Dis 2021 Feb 17. Epub 2021 Feb 17.

Public Health Ontario, Sunnybrook Health Sciences Center, ICES, Institute of Health Policy Management and Evaluation, University of Toronto, Toronto , ON, Canada.

Background: The role of antibiotics in preventing urinary tract infection (UTI) in older adults is unknown. We sought to quantify the benefits and risks of antibiotic prophylaxis among older adults.

Methods: We conducted a matched cohort study comparing older adults (≥66 years) receiving antibiotic prophylaxis, defined as antibiotic treatment for at least 30 days starting within 30 days of a positive culture, to patients with positive urine cultures that received antibiotic treatment but did not receive prophylaxis. We matched each prophylaxis recipient to 10 non-recipients based on organism, number of positive cultures, and propensity score. Outcomes included 1) emergency department (ED) visit or hospitalization for UTI, sepsis, or bloodstream infection within 1 year; 2) acquisition of antibiotic resistance in urinary tract pathogens; 3) antibiotic-related complications.

Results: Overall 4.7% (151/3,190) of UTI prophylaxis patients and 3.6% (n=1,092/30,542) controls required an ED visit or hospitalization for UTI, sepsis, or bloodstream infection (Hazard Ratio (HR) 1.33, 95%CI 1.12 to 1.57). Acquisition of antibiotic resistance to any urinary antibiotic (HR 1.31, 95%CI 1.18 to 1.44) and to the specific prophylaxis agent (HR 2.01, 95% CI 1.80 to 2.24) were higher in patients receiving prophylaxis. While the overall risk of antibiotic-related complications was similar between groups (HR 1.08, 95%CI 0.94 to 1.22) the risk of C. difficile and general medication adverse events was higher in prophylaxis recipients (HR 1.56, 95%CI 1.05 to 2.23; HR 1.62, 95%CI 1.11 to 2.29, respectively).

Conclusions: Among older adults with UTI, the harms of long-term antibiotic prophylaxis may outweigh their benefits.
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http://dx.doi.org/10.1093/cid/ciab116DOI Listing
February 2021

Effect of Taping Face Masks on Quantitative Particle Counts Near the Eye: Implications for Intravitreal Injections in the COVID-19 Era.

Am J Ophthalmol 2021 05 31;225:166-171. Epub 2021 Jan 31.

From the Sidney Kimmel Medical College (WGS, SNP, AEK, AC, SJG, JH), Thomas Jefferson University, Philadelphia, Pennsylvania, USA; Retina Service of Wills Eye Hospital (SNP, AEK, AC, SJG, JH), Mid Atlantic Retina, Philadelphia, Pennsylvania, USA. Electronic address:

Purpose: To determine the effect of taping the top of face masks on air particle counts directed toward the eye during simulated intravitreal injections.

Design: Prospective observational crossover study.

Methods: Thirteen healthy subjects were recruited. Each wore a cloth, surgical, or N95 mask in randomized order. The number of air particles were quantified by using a particle counter suspended over the right eye while each subject breathed normally, deeply, or spoke using a standardized script. Particle counts were obtained with the top of each mask taped and not taped. The main outcome measurements were particle counts of 0.3, 0.5, 1, 3, 5, and 10 μm and total particle counts.

Results: Taping cloth masks while subjects were speaking significantly reduced particle counts for the 0.3- (P = .03), 0.5- (P = .01), and 1-μm (P = .03) particles and total particle counts (P = .008) compared to no taping. Taping the top of cloth masks during normal or deep breathing did not significantly affect particle counts compared to no taping. Taping the top of surgical or N95 masks did not significantly alter particle counts for any breathing condition tested.

Conclusions: Taping the top of cloth masks prior to simulated intravitreal injections significantly reduced air particle counts directed toward the eye when subjects were speaking compared to no taping. This may have implications for decreasing air particles reaching the eye during intravitreal injections, including aerosolized droplets from a patient's mouth that may carry oral pathogens.
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http://dx.doi.org/10.1016/j.ajo.2021.01.021DOI Listing
May 2021

Endophthalmitis following Intravitreal Anti-Vascular Endothelial Growth Factor Therapy: Changes in Incidence and Outcomes over a 9-Year Period.

Curr Eye Res 2021 Jan 31:1-8. Epub 2021 Jan 31.

Mid Atlantic Retina, The Retina Service of Wills Eye Hospital, Philadelphia, Pennsylvania, USA.

: To evaluate whether the incidence, microbial spectrum, and visual outcomes of endophthalmitis following intravitreal injections have changed over time.: Retrospective cohort study of endophthalmitis in eyes receiving intravitreal injection of anti-vascular endothelial growth factor between 2009-2012 and 2016-2017 at a single, large retina practice.: A total of 283,315 injections resulted in 96 suspected infectious endophthalmitis cases. Comparing 2009-2012 and 2016-2017, the rate of suspected endophthalmitis changed from 1 in 2,663 injections to 1 in 3,195 injections ( = .37). Visual outcomes 6 months after endophthalmitis were significantly better during the latter period ( = .04), with an average loss of 6.3 lines of VA in 2009-2012 compared to a loss of 3.6 lines in 2016-2017. In multivariate analysis, a "no-talking" policy during injections resulted in a trend towards a decrease in endophthalmitis incidence ( = .08). Cessation of post-injection topical antibiotic use did not independently decrease endophthalmitis incidence ( = .24) when the effect of a "no-talking" policy was taken into account. A lower rate of endophthalmitis was seen after prefilled vs. conventionally prepared ranibizumab syringe use for injection (0.014% vs. 0.035%, respectively), though this difference did not meet statistical significance ( = .16).: The incidence of endophthalmitis after intravitreal injection decreased and visual outcomes improved between the periods of 2009-2012 and 2016-2017. A "no-talking" policy during injections was associated with a trend toward a decrease in endophthalmitis rate.
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http://dx.doi.org/10.1080/02713683.2021.1874023DOI Listing
January 2021

Quantification of Scopoletin from Roots of Argyreia Speciosa (Linn. F) Sweet Using HPLC through the Concept of Design of Experiment.

J AOAC Int 2021 Jan 30. Epub 2021 Jan 30.

Department of Pharmaceutics and Pharmaceutical Technology, Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, CHARUSAT-Campus, Changa-, 388421, Anand, Gujarat, India.

Background: Roots of Argyreia speciosa (Linn. F) Sweet (family: Convolvulaceae) are used in Ayurveda to treat male reproductive and nervous system disorders.

Objective: Isolation of scopoletin from the roots of Argyreia speciosa, development and validation of an analytical method using HPLC for the quantification of scopoletin from the root powder of Argyreia speciosa.

Method: Scopoletin was isolated from chloroform fraction prepared from hydrolyzed methanolic extract and identified using spectral studies. A reverse-phase HPLC based analytical method was developed and optimized using the DoE approach to estimate scopoletin from the roots of Argyreia speciosa. Scopoletin was separated and quantified using HPLC containing C18 column and a PDA detector. The optimized mobile phase was methanol: water (pH∼3.2) [25: 75, %v/v].

Results: The Box-Behnken design was used to optimize chromatographic parameters and the extraction procedure. The validation studies showed a linear relationship (r2=0.998) in the range of 1-40 µg/ml. The limit of Detection and Limit of Quantification were found to be 0.28 µg/ml and 0.84 µg/ml, respectively and the recovery values were found between 91.94 to 97.86%. The developed analytical method was found robust too. The amount of scopoletin was estimated to be 0.024 ± 0.0016%w/w from dried root powder.

Conclusion: The recorded chromatogram and amount of scopoletin determined would serve as one of the standardization parameters to access the quality of raw material containing Argyreia speciosa.

Highlights: Developed analytical method may be adopted as a part of the standardization procedure for Argyreia speciosa in the quality control laboratory.
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http://dx.doi.org/10.1093/jaoacint/qsab013DOI Listing
January 2021

Stereotactic Radiosurgery for Perioptic Meningiomas: An International, Multicenter Study.

Neurosurgery 2021 03;88(4):828-837

Department of Radiation Oncology, University of Colorado, Denver, Colorado.

Background: Stereotactic radiosurgery (SRS) is increasingly used for management of perioptic meningiomas.

Objective: To study the safety and effectiveness of SRS for perioptic meningiomas.

Methods: From 12 institutions participating in the International Radiosurgery Research Foundation (IRRF), we retrospectively assessed treatment parameters and outcomes following SRS for meningiomas located within 3 mm of the optic apparatus.

Results: A total of 438 patients (median age 51 yr) underwent SRS for histologically confirmed (29%) or radiologically suspected (71%) perioptic meningiomas. Median treatment volume was 8.01 cm3. Median prescription dose was 12 Gy, and median dose to the optic apparatus was 8.50 Gy. A total of 405 patients (93%) underwent single-fraction SRS and 33 patients (7%) underwent hypofractionated SRS. During median imaging follow-up of 55.6 mo (range: 3.15-239 mo), 33 (8%) patients experienced tumor progression. Actuarial 5-yr and 10-yr progression-free survival was 96% and 89%, respectively. Prescription dose of ≥12 Gy (HR: 0.310; 95% CI [0.141-0.679], P = .003) and single-fraction SRS (HR: 0.078; 95% CI [0.016-0.395], P = .002) were associated with improved tumor control. A total of 31 (10%) patients experienced visual decline, with actuarial 5-yr and 10-yr post-SRS visual decline rates of 9% and 21%, respectively. Maximum dose to the optic apparatus ≥10 Gy (HR = 2.370; 95% CI [1.086-5.172], P = .03) and tumor progression (HR = 4.340; 95% CI [2.070-9.097], P < .001) were independent predictors of post-SRS visual decline.

Conclusion: SRS provides durable tumor control and quite acceptable rates of vision preservation in perioptic meningiomas. Margin dose of ≥12 Gy is associated with improved tumor control, while a dose to the optic apparatus of ≥10 Gy and tumor progression are associated with post-SRS visual decline.
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http://dx.doi.org/10.1093/neuros/nyaa544DOI Listing
March 2021

Preliminary Study of the Effects of Eccentric-Overload Resistance Exercise on Physical Function and Torque Capacity in Chronic Kidney Disease.

J Funct Morphol Kinesiol 2020 Dec 18;5(4). Epub 2020 Dec 18.

Department of Physical Medicine and Rehabilitation, University of Colorado, Aurora, CO 80045, USA.

The purpose of this preliminary study was to describe changes in physical function and torque capacity in adults with chronic kidney disease (CKD) in response to a novel progressive eccentric-overload resistance exercise (ERE) regime. Participants included men ( = 4) diagnosed with CKD according to estimated glomerular filtration rate (eGFR) between 59 and 15 mL/kg/1.73 m and not requiring dialysis. Physical function was determined by the Short Physical Performance Battery (SPPB), five repetitions of a sit-to-stand (STS) task, and timed-up and go (TUG). Knee extensor strength was assessed using both isometric and isokinetic contractions and performance fatigability indexes were calculated during a 30-s maximal isometric test and a 30-contraction isokinetic test at 180°/second. None of the patients exhibited significant worsening in their health status after training. Participants demonstrated improvements in several measures of physical function and torque capacity following 24 sessions of ERE. Following training, performance fatigability remained relatively stable despite the increases in torque capacity, indicating the potential for greater fatigue resistance. These findings provide initial evidence for ERE as a potential treatment option to combat declines in physical function and neuromuscular impairments in people with CKD. Future research is required to determine optimal progression strategies for maximizing specific neuromuscular and functional outcomes when using ERE in this patient population.
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http://dx.doi.org/10.3390/jfmk5040097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804887PMC
December 2020

Mitochondria exert age-divergent effects on recovery from spinal cord injury.

Exp Neurol 2021 Mar 7;337:113597. Epub 2021 Jan 7.

Department of Physiology, College of Arts and Sciences, University of Kentucky, Lexington, KY 40536, USA; Spinal Cord and Brain Injury Research Center, University of College of Medicine, College of Arts and Sciences, University of Kentucky, Lexington, KY 40536, USA. Electronic address:

The extent that age-dependent mitochondrial dysfunction drives neurodegeneration is not well understood. This study tested the hypothesis that mitochondria contribute to spinal cord injury (SCI)-induced neurodegeneration in an age-dependent manner by using 2,4-dinitrophenol (DNP) to uncouple electron transport, thereby increasing cellular respiration and reducing reactive oxygen species (ROS) production. We directly compared the effects of graded DNP doses in 4- and 14-month-old (MO) SCI-mice and found DNP to have increased efficacy in mitochondria isolated from 14-MO animals. In vivo, all DNP doses significantly exacerbated 4-MO SCI neurodegeneration coincident with worsened recovery. In contrast, low DNP doses (1.0-mg/kg/day) improved tissue sparing, reduced ROS-associated 3-nitrotyrosine (3-NT) accumulation, and improved anatomical and functional recovery in 14-MO SCI-mice. By directly comparing the effects of DNP between ages we demonstrate that mitochondrial contributions to neurodegeneration diverge with age after SCI. Collectively, our data indicate an essential role of mitochondria in age-associated neurodegeneration.
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http://dx.doi.org/10.1016/j.expneurol.2021.113597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870583PMC
March 2021

Stereotactic radiosurgery for treatment of radiation-induced meningiomas: a multiinstitutional study.

J Neurosurg 2021 Jan 1:1-9. Epub 2021 Jan 1.

1Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia.

Objective: Radiation-induced meningiomas (RIMs) are associated with aggressive clinical behavior. Stereotactic radiosurgery (SRS) is sometimes considered for selected RIMs. The authors investigated the effectiveness and safety of SRS for the management of RIMs.

Methods: From 12 institutions participating in the International Radiosurgery Research Foundation, the authors pooled patients who had prior cranial irradiation and were subsequently clinically diagnosed with WHO grade I meningiomas that were managed with SRS.

Results: Fifty-two patients underwent 60 SRS procedures for histologically confirmed or radiologically suspected WHO grade I RIMs. The median ages at initial cranial radiation therapy and SRS for RIM were 5.5 years and 39 years, respectively. The most common reasons for cranial radiation therapy were leukemia (21%) and medulloblastoma (17%). There were 39 multiple RIMs (35%), the mean target volume was 8.61 ± 7.80 cm3, and the median prescription dose was 14 Gy. The median imaging follow-up duration was 48 months (range 4-195 months). RIM progressed in 9 patients (17%) at a median duration of 30 months (range 3-45 months) after SRS. Progression-free survival at 5 years post-SRS was 83%. Treatment volume ≥ 5 cm3 predicted progression (HR 8.226, 95% CI 1.028-65.857, p = 0.047). Seven patients (14%) developed new neurological symptoms or experienced SRS-related complications or T2 signal change from 1 to 72 months after SRS.

Conclusions: SRS is associated with durable local control of RIMs in the majority of patients and has an acceptable safety profile. SRS can be considered for patients and tumors that are deemed suboptimal, poor surgical candidates, and those whose tumor again progresses after removal.
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http://dx.doi.org/10.3171/2020.7.JNS202064DOI Listing
January 2021

Costs of Definitive Chemoradiation, Surgery, and Adjuvant Radiation Versus De-Escalated Adjuvant Radiation per MC1273 in HPV+ Cancer of the Oropharynx.

Int J Radiat Oncol Biol Phys 2021 Jun 23;110(2):396-402. Epub 2020 Dec 23.

Division of Radiation Oncology, University of Tennessee, Knoxville, Tennessee. Electronic address:

Purpose: De-escalated treatment for human papillomavirus (HPV)+ oropharynx squamous cell carcinoma (OPSCC) has shown promising initial results. Health-care policy is increasingly focusing on high-value care. This analysis compares the cost of care for HPV+ OPSCC treated with definitive chemoradiation (CRT), surgery and adjuvant radiation (RT), and surgery and de-escalated CRT on MC1273.

Methods And Materials: MC1273 is a prospective, phase 2 study evaluating adjuvant CRT to 30 to 36 Gy plus docetaxel for HPV+ OPSCC after surgery for high-risk patients. Matched standard-of-care control groups were retrospectively identified for patients treated with definitive CRT or adjuvant RT. Standardized costs were evaluated before radiation, during treatment (during RT), and at short-term (6 month) and long-term (7-24 month) follow-up periods.

Results: A total of 56 definitive CRT, 101 adjuvant RT, and 66 MC1273 patients were included. The CRT arm had more T3-4 disease (63% vs 17-21%) and higher N2c-N3 disease (52% vs 20-24%) vs both other groups. The total treatment costs in the CRT, adjuvant RT, and MC1273 groups were $47,763 (standard deviation [SD], $19,060], $57,845 (SD, $17,480), and $46,007 (SD, $9019), respectively, and the chemotherapy and/or RT costs were $39,936 (SD, $18,480), $26,603 (SD, $12,542), and $17,864 (SD, $3288), respectively. The per-patient, per-month, average short-term follow-up costs were $3860 (SD, $10,525), $1072 (SD, $996), and $972 (SD, $833), respectively, and the long-term costs were $978 (SD, $2294), $485 (SD, $1156), and $653 (SD, $1107), respectively. After adjustment for age, T-stage, and N-stage, treatment costs remained lower for CRT and MC1273 versus adjuvant RT ($45,450 and $47,114 vs $58,590, respectively; P < .001), whereas the total per-patient, per-month follow-up costs were lower in the MC1273 study group and adjuvant RT versus CRT ($853 and $866 vs $2030, respectively; P = .03).

Conclusions: MC1273 resulted in 10% and 20% reductions in global costs compared with standard-of-care adjuvant RT and definitive CRT treatments. Substantial cost savings may be an added benefit to the already noted low toxicity and maintained quality of life of treatment per MC1273.
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http://dx.doi.org/10.1016/j.ijrobp.2020.12.021DOI Listing
June 2021

Loop Diuretic Prescription and Long-Term Outcomes in Heart Failure: Association Modification by Congestion.

Am J Med 2021 06 28;134(6):797-804. Epub 2021 Jan 28.

Veterans Affairs Medical Center, Washington, DC; George Washington University, Washington, DC; Georgetown University, Washington, DC. Electronic address:

Background: The effect of loop diuretics on clinical outcomes in heart failure has not been evaluated in randomized controlled trials. In hospitalized patients with heart failure, a discharge loop diuretic prescription has been shown to be associated with improved 30-day outcomes, which appears to be more pronounced in subgroups with congestion. In the current study, we examined these associations and association modifications during longer follow-up.

Methods: We assembled a propensity score-matched cohort of 2191 pairs of hospitalized heart failure patients discharged with, vs without, a prescription for loop diuretics, balanced on 74 baseline characteristics (mean age 78 years; 54% women; 11% African American).

Results: Hazard ratio (HR) and 95% confidence interval (CI) for 6-year combined endpoint of heart failure readmission or all-cause mortality was 1.02 (0.96-1.09). HRs and 95% CIs for this combined endpoint in patients with no, mild-to-moderate, and severe pulmonary rales were 1.19 (1.07-1.33), 0.95 (0.86-1.04), and 0.77 (0.63-0.94), respectively (P for interaction, < .001). Respective HRs (95% CIs) for no, mild-to-moderate, and severe lower extremity edema were 1.16 (1.06-1.28), 0.94 (0.85-1.04), and 0.71 (0.56-0.89; interaction P < .001).

Conclusions: The association between a discharge loop diuretic prescription and long-term clinical outcomes in hospitalized patients with heart failure is modified by admission congestion with worse, neutral, and better outcomes in patients with no, mild-to-moderate, and severe congestion, respectively. If these findings can be replicated, congestion may be used to risk-stratify patients with heart failure for potential optimization of loop diuretic prescription and outcomes.
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http://dx.doi.org/10.1016/j.amjmed.2020.11.019DOI Listing
June 2021