bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterizing and Measuring Tuberculosis Stigma in the Community: A Mixed-Methods Study in Cambodia
Authors: Teo Alvin Kuo Jing , Tan Rayner Kay Jin , Smyth Caoimhe , Soltan Viorel , Eng Sothearith , Ork Chetra , Sok Ngovlyly , Tuot Sovannary , Hsu Li Yang , Yi Siyan
Published: September 2020

Background

Stigma is a significant barrier to healthcare and a factor that drives the global burden of tuberculosis (TB). However, there is a scarcity of information on TB stigma in developing countries. We aimed to characterize, measure, and explore the determinants of TB stigma among people with TB in Cambodia.

Methods

We conducted a mixed-methods study between February and August 2019 using a triangulation convergent design—a cross-sectional survey (n = 730) and nested in-depth interviews (n = 31) among people with TB. Quantitative data were analyzed using descriptive statistics and generalized linear regression models. Qualitative transcripts were thematically analyzed.

Results

A total of 56% and 51% of participants experienced self-stigma and perceived stigma by the community, respectively. We found rural dwellers, knowledge of how TB is transmitted, and knowledge that anybody can get TB were associated with higher levels of self-stigma and perceived stigma by the community. Higher scores on knowledge of TB symptoms were inversely associated with both self-stigma and community stigma. Thematic analyses revealed accounts of experienced stigma, acts of intentional distancing and hiding TB diagnosis from others, and feelings of embarrassment and shame.

Conclusions

Tuberculosis stigma was prevalent, suggesting a need for the incorporation of stigma-reduction strategies in the national TB responses. These strategies should be contextualized and developed through community engagement. Future research should continue to measure the levels and dimensions of TB stigma among people with TB through behavioral surveillance using standardized tools.
Comprehensive care of the ambulatory child with cerebral palsy (GMFCS I and II): A Canadian perspective
Authors: Kawamura Anne , Makino Amber , McLeod Scott
Published: September 2020

In Canada, cerebral palsy (CP) is the most common physical disability, affecting approximately 2 to 3 per 1,000 individuals. Paediatricians are sure to encounter and care for children with CP and their families. The role of the general paediatrician in caring for a child with CP is crucial, from diagnosis to providing a ‘medical home’, and from ensuring care coordination to delivering anticipatory guidance and preventive health and wellness care. The CP Health and Wellness Record that accompanies this practice point can assist both practitioners and children’s families by exploring key areas of health, function, participation, and wellness. This record may be used alongside other evidence-based health promotion guides, such as the Rourke Baby Record and the Greig Health Record, to prompt clinicians caring for ambulatory children with CP (Gross Motor Function Classification System [GMFCS] levels I and II) on specific health issues and domains.
Safety of intravenous anakinra in COVID-19 with evidence of hyperinflammation, a case series
Authors: Clark Kristina E N , Collas Oliver , Lachmann Helen , Singh Animesh , Buckley Jim , Bhagani Sanjay
Published: September 2020

Objectives

Anakinra is a selective IL-1 inhibitor, which has been used in the context of secondary haemophagocytic lymphohistiocytosis. Although usually given in the s.c. form, previous anecdotal reports have emphasized its utility when given i.v. Our aim is to report our experience on the beneficial effects of anakinra i.v. in patients with SARS-CoV-2 and evidence of hyperinflammation.

Methods

We report four patients with severe COVID-19 infection requiring intensive care admission and ventilatory support.

Results

All four patients showed evidence of deterioration, with hyperferritinaemia and increasing oxygen requirements and with superadded bacterial infections. Upon commencement of anakinra i.v., there was subsequent improvement in the patients clinically, with reduction in ventilatory support and inotropic support, and biochemically, with rapid improvement in inflammatory markers.

Conclusion

Anakinra is safe to use i.v. in patients with COVID-19 and evidence of superadded bacterial infection. Although its utility has not been confirmed in a randomized trial, current research in the COVID-19 pandemic aims to establish the utility of immunosuppression, including IL-1 blockade, on the outcomes of patients with moderate to severe disease. Our case series supports its use in patients with severe, life-threatening COVID-19 and evidence of hyperinflammation.
Sleep deficits and cannabis use behaviors: an analysis of shared genetics using linkage disequilibrium score regression and polygenic risk prediction
Authors: Winiger Evan A , Ellingson Jarrod M , Morrison Claire L , Corley Robin P , Pasman Joëlle A , Wall Tamara L , Hopfer Christian J , Hewitt John K
Published: September 2020

Study Objectives

Estimate the genetic relationship of cannabis use with sleep deficits and an eveningness chronotype.

Methods

We used linkage disequilibrium score regression (LDSC) to analyze genetic correlations between sleep deficits and cannabis use behaviors. Secondly, we generated sleep deficit polygenic risk score (PRS) and estimated their ability to predict cannabis use behaviors using linear and logistic regression. Summary statistics came from existing genome-wide association studies of European ancestry that were focused on sleep duration, insomnia, chronotype, lifetime cannabis use, and cannabis use disorder (CUD). A target sample for PRS prediction consisted of high-risk participants and participants from twin/family community-based studies (European ancestry; n = 760, male = 64%; mean age = 26.78 years). Target data consisted of self-reported sleep (sleep duration, feeling tired, and taking naps) and cannabis use behaviors (lifetime ever use, number of lifetime uses, past 180-day use, age of first use, and lifetime CUD symptoms).

Results

Significant genetic correlation between lifetime cannabis use and an eveningness chronotype (rG = 0.24, p < 0.001), as well as between CUD and both short sleep duration (<7 h; rG = 0.23, p = 0.017) and insomnia (rG = 0.20, p = 0.020). Insomnia PRS predicted earlier age of first cannabis use (OR = 0.92, p = 0.036) and increased lifetime CUD symptom count (OR = 1.09, p = 0.012).

Conclusion

Cannabis use is genetically associated with both sleep deficits and an eveningness chronotype, suggesting that there are genes that predispose individuals to both cannabis use and sleep deficits.
Protecting the Flock or Policing the Sheep? Differences in School Resource Officers’ Perceptions of Threats by School Racial Composition
Authors: Fisher Benjamin W , Higgins Ethan M , Kupchik Aaron , Viano Samantha , Curran F Chris , Overstreet Suzanne , Plumlee Bryant , Coffey Brandon
Published: September 2020

Law enforcement officers (often called school resource officers or SROs) are an increasingly common feature in schools across the United States. Although SROs’ roles vary across school contexts, there has been little examination of why. One possible explanation is that SROs perceive threats differently in different school contexts and that the racial composition of schools may motivate these differences. To investigate this possibility, this study analyzes interviews with 73 SROs from two different school districts that encompass schools with a variety of racial compositions. Across both districts, SROs perceived three major categories of threats: student-based, intruder-based, and environment-based threats. However, the focus and perceived severity of the threats varied across districts such that SROs in the district with a larger proportion of White students were primarily concerned about external threats (i.e., intruder-based and environment-based) that might harm the students, whereas SROs in the district with a larger proportion of Black students were primarily concerned with students themselves as threats. We consider how these results relate to understandings of school security, inequality among students, racially disparate experiences with school policing, and school and policing policy.
Lack of In Vivo Mutagenicity of Acetamide in a 13-Week Comprehensive Toxicity Study Using F344 gpt Delta Rats
Authors: Nakamura Kenji , Ishii Yuji , Takasu Shinji , Nohmi Takehiko , Shibutani Makoto , Ogawa Kumiko
Published: September 2020

Acetamide, a food contaminant, has been shown to induce hepatocellular tumors in rats. However, the mode of action underlying acetamide-induced hepatocarcinogenesis remains unclear. In the current study, we aimed to examine the possible involvement of in vivo mutagenicity in hepatocarcinogenesis of acetamide and evaluate its toxicological profile using a comprehensive medium-term toxicity study in gpt delta rats. Six-week-old male F344 gpt delta rats were given a basal diet containing 0%, 0.625%, 1.25%, or 2.5% acetamide for 13 weeks. In general toxicologic assessment, hepatotoxic parameters in serum, such as aspartate aminotransferase and alanine aminotransferase were significantly changed at the 1.25% group and higher. Histopathological examination of the liver revealed that various changes related to hepatic injury were observed at the 1.25% group and higher. Interestingly, Feulgen-positive cytoplasmic inclusion was frequently observed in hepatocytes in these groups. In the hematopoietic system, red blood cell parameters in plasma, such as mean corpuscular volume and mean corpuscular hemoglobin were significantly changed at the 1.25% group and higher, and decrease of erythroblast in the spleen was observed histopathologically in the 2.5% group. Thus, the no-observed-adverse-effect level of acetamide in this study was 0.625% (equivalent to 394 mg/kg body weight/day). In vivo mutation assays showed that acetamide induced no changes in gpt and red/gam gene mutant frequencies, even at the carcinogenic target site. In contrast, Ki67-positive hepatocytes were increased significantly at carcinogenic doses. Therefore, these results suggested that cell proliferation activity, but not mutagenicity, played crucial roles in acetamide-induced hepatocarcinogenesis in rats.
Thromboelastography to Detect Hypercoagulability and Reduced Fibrinolysis in Coronavirus Disease 2019 Acute Respiratory Distress Syndrome Patients
Authors: Sadd Corey , Rowe Timothy , Nazeef Moniba , Kory Pierre , Sultan Samir , Faust Hilary
Published: September 2020

Objectives:

Microvascular thrombosis contributes to acute respiratory distress syndrome pathophysiology and has been demonstrated in coronavirus disease 2019-associated acute respiratory distress syndrome. Clinical laboratory measurements of coagulation and disseminated intravascular coagulation, such as coagulation factor function, platelet count, and fibrinogen, may not fully reflect the extent of microvascular thrombosis present in these patients. We investigated thromboelastography in patients with coronavirus disease 2019-associated acute respiratory distress syndrome with the objective of characterizing suspected coagulopathy and impaired fibrinolysis.

Design:

Retrospective observational cohort study.

Setting:

Single-center academic medical center.

Patients:

Ten patients with polymerase chain reaction-confirmed coronavirus disease 2019 disease complicated by acute respiratory distress syndrome.

Interventions:

Measurement of thromboelastography (n = 10) and thrombolysis with alteplase (n = 4).

Measurements and Main Results:

Hypercoagulability and decreased or absent fibrinolysis were demonstrated by thromboelastography. Thrombocytopenia and hypofibrinogenemia were not observed, while seven of 10 patients had elevated d-dimer values. For patients who received thrombolytic therapy, repeat thromboelastography demonstrated improvements in coagulation index and lysis at 30 minutes reflecting reduced hypercoagulability and increased fibrinolysis. One major bleeding complication was detected following thrombolysis. Eight of 10 patients survived and were successfully extubated, and six of 10 have since been discharged.

Conclusions:

In coronavirus disease 2019 patients with acute respiratory distress syndrome in whom thromboelastography was performed, hypercoagulability and impaired fibrinolysis were observed. In the context of autopsy studies demonstrating pulmonary microvascular thromboses in coronavirus disease 2019 patients, noninvasive detection of hypercoagulability and deficient fibrinolysis in coronavirus disease 2019 acute respiratory distress syndrome using thromboelastography could improve understanding and management of coronavirus disease 2019.
A Randomized Controlled Trial of Antithrombin Supplementation During Extracorporeal Membrane Oxygenation
Authors: Panigada Mauro , Cucino Alberto , Spinelli Elena , Occhipinti Giovanna , Panarello Giovanna , Novembrino Cristina , Consonni Dario , Protti Alessandro , Lissoni Alfredo , Arcadipane Antonio , Pesenti Antonio , Grasselli Giacomo
Published: September 2020

Objectives:

Supplementation of antithrombin might decrease the amount of heparin needed to achieve a given anticoagulation target during extracorporeal membrane oxygenation. However, exogenous antithrombin itself may increase the risk of bleeding. We conceived a study to evaluate the effect of antithrombin supplementation in adult patients requiring venovenous extracorporeal membrane oxygenation for respiratory failure on heparin dose, adequacy of anticoagulation, and safety.

Design:

Prospective randomized controlled trial.

Setting:

ICUs of two Italian referral extracorporeal membrane oxygenation centers.

Patients:

Adult patients requiring venovenous extracorporeal membrane oxygenation for severe respiratory failure and unfractionated heparin for systemic anticoagulation.

Interventions:

Before extracorporeal membrane oxygenation start, patients were randomized to either receive antithrombin concentrate to maintain a plasmatic level 80–120% (treatment) or not (control) during the extracorporeal membrane oxygenation course.

Measurements and Main Results:

The primary outcome was the total amount of heparin required to maintain activated partial thromboplastin time ratio 1.5–2. Secondary outcomes were anti-factor Xa, the incidence of hemorrhagic and thrombotic events, and the amount of blood products transfused. Twenty-four patients in the treatment group and 24 in the control group were included in the intention-to-treat analysis. Antithrombin was 109.5% (93.0–123.0%) in the treatment group and 84.0% (68.5–98.0%) in the control group (p = 0.001). Supplementation of antithrombin did not decrease heparin dose (13.5 international units/kg/hr [9.6–17.9 international units/kg/hr] vs 15.1 international units/kg/hr [10.7–18.3 international units/kg/hr] in the treatment and control group, respectively; p = 0.33) and anti-Factor Xa levels (0.4 international units/mL [0.3–0.5 international units/mL] vs 0.3 international units/mL [0.2–0.5 international units/mL] in the treatment group and control group respectively; p = 0.65). Bleeding, blood product transfusions, and thrombosis were not different in the two groups.

Conclusions:

Antithrombin supplementation may not decrease heparin requirement nor diminish the incidence of bleeding and/or thrombosis in adult patients on venovenous extracorporeal membrane oxygenation.
Prognostic analysis of recurrence in children and adolescents with differentiated thyroid cancer
Authors: Wang Xing , Wang Xiao-Lei
Published: September 2020

Background:

The standard treatment for pediatric differentiated thyroid carcinoma (DTC) still requires consideration because of a lack of clinical evidence. The purpose of this study was to summarize the clinical experiences and explore the risk factors for post-operative recurrence through a retrospective analysis to develop better clinical strategies for pediatric DTC.

Methods:

This study retrospectively analyzed children and adolescents with DTC who were treated between January 1999 and December 2014 at the Cancer Hospital, Chinese Academy of Medical Sciences. Clinicopathological results and outcomes were collected. A log-rank test of Kaplan-Meier curves and the Cox regression model were used to determine the factors associated with recurrence.

Results:

Data of 150 patients were collected in this study. During the follow-up, there was only one disease-related death. The recurrence rates at 3, 5, and 10 years were 13.6%, 18.7%, and 28.6%, respectively. There was a significant difference in the rate of recurrence according to age (P < 0.001), extrathyroidal extension (P < 0.001), lymph node metastasis (P = 0.023), and invasion of the trachea and esophageal wall (P = 0.004). Cox regression analysis demonstrated that age (P = 0.006) and extrathyroidal extension (P = 0.013) were significant dependent factors of post-operative recurrence.

Conclusions:

The prognosis of DTC in children and adolescents is favorable. A close follow-up is recommended because of the high recurrence rate. A comparatively higher recurrence rate was observed in the younger age group, and new age-based divisions may be needed to conveniently evaluate the possibility of recurrence.
Use of Nonsteroidal Anti-inflammatory Drugs for COVID-19 Infection: Adjunct Therapy?
Authors: Zhao Daniel , Zhang Sandy , Igawa Teryn , Frishman William
Published: September 2020

Severe acute respiratory distress syndrome coronavirus 2 (COVID-19) is the cause of the current pandemic, which remains a tremendous cause of morbidity and mortality worldwide. Although there are numerous trials underway, there is currently no medication known to cure the infection. Nonsteroidal anti-inflammatory drugs (NSAIDs) are inexpensive, widely available medications with antiviral and anti-inflammatory properties and may have utility as an adjunct therapy to improve outcomes in patients with severe COVID-19 infection. A thorough PubMed literature review on the therapeutic use of NSAID was conducted to provide a comprehensive perspective of the role of NSAIDs in treating COVID-19. NSAIDs may be a useful adjunct therapy for patients with severe COVID-19 infection, but further investigation and clinical trials are necessary to ensure their safety and efficacy.
Association Between Arsenic Exposure and Cardiovascular Disease
Authors: Kononenko Mariya , Frishman William H.
Published: September 2020

Arsenic is a ubiquitously dispersed metalloid that has been implicated as the cause of various adverse health effects. Human exposure to arsenic primarily occurs through contaminated drinking water and dietary intake of rice and grains, posing a great public health risk to millions of people worldwide. High levels of arsenic have been positively associated with incident cardiovascular disease (CVD). In the last decade, a growing body of evidence has established a role for low-to-moderate arsenic exposure in CVD risk as well. The molecular mechanism of action by which arsenic induces cardiovascular toxicity is not completely understood, but epigenetic changes, increased platelet aggregation, and increased oxidative stress have all been implicated. Presently, there is a substantial amount of retrospective and prospective cohort studies supporting the role of arsenic in CVD, although randomized controlled trials have yet to be conducted. In this review, we have sought to summarize the existing high-quality evidence elucidating arsenic’s role in CVD development and to evaluate the need for future research.
Recurrence of Acute Right Colon Diverticulitis Following Nonoperative Management: A Systematic Review and Meta-analysis
Authors: Lee Yongjin F. , Tang Dalun D. , Patel Samik H. , Battaglia Michael A. , Shanker Beth-Ann , Cleary Robert K.
Published: September 2020

BACKGROUND:

There are currently no guidelines on the management of right colon diverticulitis. Treatment options have been extrapolated from the management of left-sided diverticulitis. Gaining knowledge of the risk and morbidity of diverticulitis recurrence is integral to weighing the benefit of elective surgery for right-sided diverticulitis.

OBJECTIVE:

The purpose of this study was to summarize the recurrence rate and the morbidity of recurrence of Hinchey classification I/II, right-sided diverticulitis following nonoperative management.

DATA SOURCES:

PubMed, EMBASE, and Cochrane Database of Collected Reviews were searched up to June 2019.

STUDY SELECTION:

Observational cohort studies evaluating outcomes following nonoperative management were reviewed. No randomized controlled trials were available.

INTERVENTIONS:

Intravenous antibiotics with or without percutaneous drainage of associated abscess were administered.

MAIN OUTCOME MEASURES:

The primary outcomes measured were the recurrence rate and morbidity associated with recurrence. Two independent investigators extracted data. The rates of recurrence were pooled by using a random-effects model.

RESULTS:

There were 1584 adult participants from a total of 11 studies (9 retrospective cohort and 2 prospective cohort studies) included in the analysis. Over a median follow-up period of 34.2 months, the pooled recurrence rate was 12% (95% CI, 10%–15%). Twenty of 202 patients (9.9%) required urgent surgery at the time of first recurrence. There was no mortality. Subset analysis excluding 3 studies that included percutaneous drainage as a nonoperative treatment option did not change the recurrence rate (12% (95% CI, 9%–15%)) or heterogeneity. Funnel plot assessment revealed no publication bias.

LIMITATIONS:

There were no randomized controlled trials available. The statistical heterogeneity was moderate (I
2 = 46%).

CONCLUSIONS:

Nonoperative management of Hinchey I/II right-sided diverticulitis is safe and feasible. The recurrence rate is relatively low, and complications that require urgent operation are uncommon.

PROSPERO:

CRD42019131673
Extended Total Mesorectal Excision Based on the Avascular Planes of the Retroperitoneum for Locally Advanced Rectal Cancer with Lateral Pelvic Sidewall Invasion
Authors: Beppu Naohito , Ikeda Masataka , Kimura Kei , Kataoka Kozo , Yamano Tomoki , Uchino Motoi , Ikeuchi Hiroki , Tomita Naohiro
Published: September 2020

INTRODUCTION:

It has been considered difficult to achieve en bloc resection in cases of locally advanced rectal cancer with lateral pelvic sidewall invasion. The present study demonstrates a novel surgical procedure for these tumors.

TECHNIQUE:

There are 3 avascular planes of the retroperitoneum in the pelvic sidewall. Two visceral pelvic fasciae, namely the ureterohypogastric fascia and umbilical prevesical fascia, and the parietal pelvic fascia can be identified. In addition, the key structures of these fasciae, the ureter, umbilical artery, and external iliac vessels, can be identified transperitoneally before any dissection. Thus, these 3 avascular planes can be dissected without resorting to dissection of the retrorectal space. The key steps to this technique are: 1) after dissection from the side opposite to the site of tumor invasion to the dorsal side of the rectum, the avascular planes of the retroperitoneum among the 3 above-mentioned fasciae are dissected; and 2) the retrorectal space and pelvic sidewall space are connected by sharp dissection.

RESULTS:

Recognizing the 3 above-mentioned fasciae enables the dissection of the avascular planes of the pelvic sidewall, which helps to achieve en bloc dissection in cases of locally advanced rectal cancer with lateral pelvic sidewall invasion.

CONCLUSION:

The pelvic sidewall could be divided into 3 areas based on the visceral pelvic fasciae, which has helped to achieve en bloc dissection in cases of locally advanced rectal cancer with lateral pelvic sidewall invasion.
Diagnosis and Treatment of Anal Squamous Cell Carcinoma
Authors: Gardner Ivy H. , Watson Katherine M.
Published: September 2020

Case Summary:

A 61-year-old woman with ongoing tobacco use was referred to a colorectal surgery clinic after a screening colonoscopy found irregular lesions at the dentate line with biopsies revealing a high-grade squamous intraepithelial lesion. She reported scant bleeding and irregular bowel function, but no incontinence. She has a history of abnormal Papanicolaou tests, but has since undergone a hysterectomy and has no history of immunosuppressive treatment or HIV. She was taken for an examination under anesthesia that revealing a 2.5-cm mass in the anal canal and was biopsied. Pathological examination confirmed anal squamous cell carcinoma (ASCC) with strongly positive p16 staining. A CT of her chest, abdomen, and pelvis did not reveal metastatic disease. She was referred to medical and radiation oncology for radiation therapy with concurrent chemotherapy (5-fluorouracil (5-FU) and mitomycin C). Subsequent office examination with anoscopy 3 months after treatment demonstrated an anterior scar without residual tumor.
Preliminary Report on a Novel Virtual Reality Perimeter Compared With Standard Automated Perimetry
Authors: Razeghinejad Reza , Gonzalez-Garcia Alberto , Myers Jonathan S. , Katz L. Jay
Published: September 2020

Precis:

The VisuALL head-mounted perimetry in normal subjects and glaucoma patients had a moderate to strong correlation with the Humphrey Field Analyzer (HFA).

Purpose:

Visual field testing has a vital role in diagnosing and managing glaucoma. The current clinical practice relies on large, table-based testing units. This study investigated the performance of a novel virtual reality head-mounted visual perimetry device (VisuALL), in normal and glaucoma patients.

Methods:

This prospective observational study was conducted on 50 eyes of 25 healthy subjects (normal group) and 52 eyes of 26 patients with a controlled mild or moderate stage of glaucoma (glaucoma group). All participants had visual field testing with VisuALL and the HFA (24-2, Swedish Interactive Threshold Algorithm). The mean sensitivity of the whole visual field and each quadrant were compared between both machines and the receiver operating characteristic was used to compare the diagnostic abilities and the Bland-Altman plot to evaluate the agreement of the 2 perimeters.

Results:

The global mean sensitivity of the VisuALL and the HFA correlated significantly in both normal (r=0.5, P=0.001) and glaucoma (r=0.8, P<0.001) groups. The mean sensitivity of all quadrants also correlated significantly in both groups. The VisuALL mean sensitivity had a greater (0.98) receiver operating characteristic curve than HFA (0.93) mean sensitivity (P=0.06) in discriminating normal versus glaucoma.

Conclusion:

There was an excellent correlation between the VisuALL and the Standard Automated Perimetry in normal and glaucoma patients and VisuALL showing high diagnostic performance.
Safe practice ventilation technique in lung scanning for pulmonary embolism
Authors: Mayes Christopher Duncan
Published: September 2020

Ventilation/Perfusion scanning for suspected pulmonary embolism is undergoing a renaissance due to the advent of single-photon emission computed tomography (SPECT). The scan protocol demands the inhalation of a radioactive gas or vapour for the ventilation scan. The purpose of this article is to report the radioactive environmental contamination that can occur when Tc99m Technegas vapours are administered to patients for the ventilation SPECT scan. This contamination can concentrate within gamma camera heads to degrade images and is also a radiation hazard to staff. A method for sequestrating this airborne contamination was investigated using an ultra-low particulate air filter. The prevalence of radioactive contamination and the levels of contamination captured were quantified and only 36% of patients were found to have undergone the ventilation procedure without producing significant airborne contamination. Advice is given on best practice that will minimize airborne contamination and minimize the risks to staff working in the Nuclear Medicine department. The use of an extraction/filtration device may be seen as an effective additional control measure against airborne radioactive contamination for health professionals.
Pilot study comparing dominant intraprostatic lesion volume using Ga-68 prostate-specific membrane antigen PET-computed tomography and multiparametric MRI
Authors: Sasidharan Ajay , Murthy Vedang , Natarajan Aravintho , Agarwal Archi , Ranagrajan Venkatesh , Gudi Suresh , Singh Somesh , Popat Palak
Published: September 2020

Purpose

The standard imaging used for delineation of dominant intraprostatic lesion (DIL) is multiparametric MRI (mpMRI). The use of biologic imaging such as Ga-68 prostate-specific membrane antigen (PSMA) PET-computed tomography (PET-CT) for this purpose is being explored in view of increased sensitivity of this modality and the associated ease of delineation.

Materials and methods

The primary objective of the study was to compare the autogenerated volumes of the DIL in Ga-68 PSMA PET-CT with the standard volume delineated in mpMRI. Twenty patients with biopsy-proven untreated prostatic adenocarcinoma were included. Multiple percentages of the maximum standardized uptake value (%SUVmax) were used to autogenerate DIL volumes in Ga-68 PSMA PET-CT and these volumes were numerically matched with the consensus DIL volume in mpMRI. PSMA tumor volume (PSMA-TV) and total lesion PSMA (TL-PSMA) were also calculated for each lesion.

Results

Median volume of DIL in mpMRI was 4 cm3 (interquartile range, IQR = 2.5–7.6 cm3). The IQR for interobserver variability was 0.5–2.5 cm3. Median SUVmax of the DIL was 14.1 (IQR = 10.2–22.3). Median %SUVmax corresponding to mpMRI volume was 41% of SUVmax (IQR = 34–55%). There was a strong negative correlation between MRI volume and %SUVmax (r = −0.829, P < 0.001). There was a significant correlation between TL-PSMA and prostate-specific antigen (r = 0.609, P = 0.004).

Conclusions

The median DIL volume was 4 cm3 and median %SUVmax corresponding to MR volume of DIL was 41%. A strong inverse relationship is found between mpMRI-defined DIL volume and the %SUVmax which generates similar volume in Ga-68 PSMA PET-CT. TL-PSMA could be a quantitative biomarker for tumor load and prognosis.
Comparison of 18F-DCFPyL and 18F-FDG PET/computed tomography for the restaging of clear cell renal cell carcinoma: preliminary results of 15 patients
Authors: Liu Yachao , Wang Guanyun , Yu Hongkai , Wu Yue , Lin Mu , Gao Jiangping , Xu Baixuan
Published: September 2020

Objectives

This study aimed to compare the diagnostic performance of 18F-DCFPyL and 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG PET/computed tomography in the restaging of clear cell renal cell carcinoma after nephrectomy.

Methods

In this retrospective study, a total of 15 patients with suspected local recurrence of clear cell renal cell carcinoma or metastasis after surgery underwent both 18F-DCFPyL and 18F-FDG PET/computed tomography. A systematic comparison of the maximum standardized uptake value and the target to background ratio was carried out between the lesions detected by the two tracers.

Results

A total of 42 lesions were detected either by 18F-DCFPyL PET/computed tomography or by 18F-FDG PET/computed tomography. 18F-DCFPyL PET/computed tomography, but not 18F-FDG PET/computed tomography, accurately distinguished the two local recurrence from four postoperative changes. The remaining 36 lesions were soft tissue (14) and bone lesions (22); all 36 lesions were detected by 18F-DCFPyL PET/computed tomography while only 10 (10/14) soft tissue lesions and 12 (12/22) bone lesions were detected by 18F-FDG PET/computed tomography. The higher detection rate of soft tissue lesions using 18F-DCFPyL PET/computed tomography was not statistically significant (P = 0.125); however, 18F-DCFPyL PET/computed tomography was statistically better (P = 0.002) at detecting bone lesions. The average maximum standardized uptake value and target to background ratio of 18F-DCFPyL were significantly higher than that of 18F-FDG for soft tissue lesions (maximum standardized uptake value P = 0.005; target to background ratio P = 0.028) and bone lesions (maximum standardized uptake value P = 0.001; target to background ratio P = 0.001).

Conclusions

Our preliminary results indicated that 18F-DCFPyL PET/computed tomography is superior to 18F-FDG PET/computed tomography for the detection of local recurrence at both the surgical site and in bone metastasis while the tracers are comparable in the detection of soft tissue metastases.
Novel Therapeutic Approaches and the Evolution of Drug Development in Advanced Kidney Cancer
Authors: Ravi Praful , Bakouny Ziad , Schmidt Andrew , Choueiri Toni K.
Published: September 2020

Therapies currently approved in renal cell carcinoma (RCC) include tyrosine kinase inhibitors, immune checkpoint inhibitors, and inhibitors of mTOR signaling. Increased understanding of the biology of clear cell and non–clear cell RCC has led to development of agents that target hypoxia-inducible factor 2 and MET, while there is ongoing exploration of targeting immune pathways other than the programmed death ligand 1 or cytotoxic T-lymphocyte–associated protein 4 checkpoints. Drug development in RCC is moving toward the study of combination therapies and attempting to use a risk-adapted approach in treatment. While the past decade has seen the approval of several new therapies, there is an urgent need to focus drug development on novel targets and expand the therapeutic armamentarium in both clear cell and non–clear cell kidney cancer. This review provides an overview of the key targets currently undergoing clinical evaluation, as well as how drug development has evolved over the past 20 years and what the new few years may hold.
Neurologic Characterization of Craniosynostosis: Can Direct Brain Recordings Predict Language Development?
Authors: Wu Robin , Nie James , Abraham Paul , Halligan Taylor , Gabrick Kyle , Peck Connor J. , Sawh-Martinez Rajendra , Steinbacher Derek M. , Alperovich Michael , McPartland James , Persing John A.
Published: September 2020

Purpose:

Nonsyndromic craniosynostosis (NSC) is associated with language deficits. Conventional tests, such as the Bayley Scales of Infant Development (BSID), may not reflect accurate long-term cognition. Alternatively, mismatch negativity (MMN) waves recorded via electroencephalogram (EEG) measure neural responses to speech and may objectively predict language development. This study aimed to (1) correlate infant MMN to future language achievement and (2) compare MMN among subtypes of NSC.

Methods:

Pre and postoperatively (mean operative age 9.5 months), NSC participants received the BSID and EEG phoneme-discrimination paradigm(80 dB,250 Hz). The MMN was the largest negative amplitude in the difference wave 80 to 300 ms after stimuli. To measure cognitive outcome, patients completed a neurodevelopmental battery (Wechsler-Abbreviated Scale of Intelligence and Wechsler-Fundamentals) at >6 years of age.

Results:

Eleven NSC patients with EEG testing in infancy were neurocognitively tested (average age 8.0 years; 27% female; 55% sagittal, 27% metopic, 9% unicoronal, 9% sagittal/metopic). The left frontal cluster MMN strongly correlated with word-reading (r = 0.713, P = 0.031), reading-comprehension (r = 0.745, P = 0.021), and language-composites (r = 0.0771, P = 0.015). Conversely, BSID scores did not yield significant predictive value (r < 0.5, P > 0.05). Follow-up event related potentials (ERP) comparison included 39 normal control, 18 sagittal, 17 metopic, 6 unilateral-coronal infants. Preoperatively, sagittal (P = 0.003) and metopic (P = 0.003) patients had attenuated left frontal MMN compared to controls. Postoperatively, the sagittal cohort was normalized to controls while metopic patients retained attenuations (P = 0.041).

Conclusion:

ERP assessment in NSC had significantly better predictive value for future neurocognition than the BSID. Preoperatively, sagittal and metopic patients had attenuated neural response to language; postoperatively, sagittal patients had improved responses in comparison to metopic patients. Use of ERP assessment may help tailor treatment for language deficits earlier in development.
Skin Necrosis and Vision Loss or Impairment After Facial Filler Injection
Authors: Rauso Raffaele , Sesenna Enrico , Fragola Romolo , Zerbinati Nicola , Nicoletti Giovanni Francesco , Tartaro Gianpaolo
Published: September 2020

Purpose of the present study is to objectively evaluate the number of severe vascular complications, represented by skin necrosis and vision loss or impairment, following facial filler injection. The investigators implemented a review of the literature including articles published on PubMed database without limitation about year of publication, including all reports concerning skin necrosis and vision loss or impairment related to the injection of fillers for cosmetic uses. The search highlighted 45 articles and a total of 164 cases of skin necrosis and vision loss or impairment after injection of different substances. The injection site most frequently associated with complications was the nose (44.5%), followed by glabella (21%), nasolabial fold (15%), and forehead (10%). Results of the present study suggest that injectable filler can cause severe complications even in expertized hands. Treatments in the new defined “Dangerous triangle” must be carefully carried out. Despite our expectations, the highest rates of sever adverse events have been associated with autologous fat transfer practice.
Utilization of Three-Dimensional Printing in Burn Mask Production
Authors: Akiki Ronald K. , Snapp William K. , Crozier Joseph W. , Woo Albert S.
Published: September 2020

Hypertrophic scarring is a significant complication of severe face and neck burns. Burn masks offer an effective treatment. However, the conventional method of making these masks has notable shortcomings. Most notably, the use of alginate to form an impression is a laborious and uncomfortable process, especially for younger patients. To optimize this practice, the authors present a novel method of burn mask production that utilizes a 3-dimensional-printed positive mold to avoid the direct placement of alginate onto burned patient skin.
Bilateral Mastoid Process Hypertrophy Associated With Severe Trismus
Authors: Sent-Doux Kimberley , Moore Mark H. , Tan Swee T.
Published: September 2020

The mastoid process, a pneumatized prominence of the temporal bone with air-filled air cells, grows with age. We present here a series of 4 patients with bilateral mastoid hypertrophy associated with severe trismus from different etiologies, and discuss the possible explanation of this observation.
Impact of COVID-19 on Oral and Maxillofacial Surgery: Preliminary Results After the Curfew
Authors: Bartella Alexander K. , Halama Dirk , Kamal Mohammad , Hahnel Sebastian , Sander Anna Katharina , Pausch Niels Christian , Lethaus Bernd
Published: September 2020

Introduction:

The COVID-19 pandemic affects basic health care in maxillofacial surgery (MFS) due to the shift in resources and the change in patient disorders treated during the pandemic. This paper aims to elucidate the medical and financial consequences driven by the measures for COVID-19 treatment in a tertiary care centre.

Material and Methods:

To evaluate the impact of pandemic measures on daily routines of MFS, the surgical schedule during the first 2 weeks after the onset of the curfew (March 2020), and to compare it with the schedule of the same period of time 1 year earlier. Furthermore, postponed surgeries as well as cancelled follow-ups are listed. The loss of earning was calculated as well as the number and kind of postponed procedures.

Results:

The number of surgeries decreased by 45% (n = 163 in 2019 vs n = 89 in 2020), and the duration of the surgeries decreased from 94.2 minutes to 62.1 minutes. No elective surgeries, such as implantology, aesthetic surgery, or orthognathic surgery, took place. Furthermore, also trauma cases decreased from 9 to 3 cases. Considering all variables, the financial loss can be calculated as approximately 100,256.50 Euros per week.

Conclusion:

The impact of COVID-19 on MFS is certainly of medical and economic importance and is related to the duration of the pandemic
COVID-19 in Solid Organ Transplantation: A Matched Retrospective Cohort Study and Evaluation of Immunosuppression Management
Authors: Miarons Marta , Larrosa-García María , García-García Sonia , Los-Arcos Ibai , Moreso Francesc , Berastegui Cristina , Castells Lluís , Pérez-Hoyos Santiago , Varela Javier , Pau-Parra Alba , Varón-Galcera Carlota , Parramon-Teixidó Carlos-Javier , Martínez-Casanova Javier , Domènech Laura , García-Ortega Patricia , Sánchez-Sancho Pablo , Alonso-Martínez Carla , Gómez-Ganda Laura , Roch-Santed Maria , Gracia-Moya Ariadna , Del-Rio-Gutiérrez José-Manuel , Guillén-Del-Castillo Alfredo , Sans-Pola Carla , Antón Andrés , Montoro Bruno , Gorgas-Torner Maria-Queralt ,   on behalf of the Vall d’Hebron COVID-19 Working Group
Published: September 2020

Background.

The epidemiological and clinical characteristics of solid organ transplant (SOT) patients during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic remains unclear. We conducted a matched retrospective cohort study to compare clinical outcomes among SOT recipients with the general population and to assess immunosuppression management.

Methods.

Adult SOT recipients with laboratory polymerase chain reaction–confirmed SARS-CoV-2 infection admitted to a tertiary-care hospital in Barcelona, Spain, from March 11 to April 25, 2020, were matched to controls (1:4) on the basis of sex, age, and age-adjusted Charlson’s Index. Patients were followed for up to 28 days from admission or until censored. Primary endpoint was mortality at 28 days. Secondary endpoints included admission to the intensive care unit and secondary complications. Drug–drug interactions (DDI) between immunosuppressants and coronavirus disease 2019 (COVID-19) management medication were collected.

Results.

Forty-six transplant recipients and 166 control patients were included. Mean (SD) age of transplant recipients and controls was 62.7 (12.6) and 66.0 (12.7) years, 33 (71.7%) and 122 (73.5%) were male, and median (interquartile range) Charlson’s Index was 5 (3–7) and 4 (2–7), respectively. Mortality was 37.0% in SOT recipients and 22.9% in controls (P = 0.51). Thirty-three (71.7%) patients underwent transitory discontinuation of immunosuppressants due to potential or confirmed DDI.

Conclusions.

In conclusion, hospitalized SOT recipients with COVID-19 had a trend toward higher mortality compared with controls, although it was not statistically significant, and a notable propensity for DDI.
Vitamin B6 Deficiency in Patients With Parkinson Disease Treated With Levodopa/Carbidopa
Authors: Rojo-Sebastián Ana , González-Robles Cristina , García de Yébenes Justo
Published: September 2020

Objective

The aim of the study was to investigate the role of L-DOPA/carbidopa (CD) therapy on vitamin B6 levels in patients with Parkinson disease (PD).

Methods

This is a cross-sectional retrospective study of vitamin B6 plasma levels in 24 patients with PD treated with L-DOPA/CD for 3 or more years, orally or intraduodenally. Vitamin B6 levels in plasma were measured by ELISA.

Results

All patients treated with intraduodenal L-DOPA/CD (6 of 6) and 13 of 18 patients receiving L-DOPA/CD orally had low plasma levels of vitamin B6. Eight of the 19 patients with low vitamin B6 levels had symptoms of hypovitaminosis B6. Patients with low vitamin B6 had been treated with larger doses of L-DOPA/CD, although the differences did not have statistical significance. Patients treated with intraduodenal L-DOPA/CD have vitamin B6 levels significantly lower than those treated with oral L-DOPA/CD. The variables that most correlated with vitamin B6 levels were the cumulative annual doses of CD (r = −0.36) and L-DOPA (r = −0.33) during the year preceding the study and the time to develop dyskinesias or fluctuations (r = +0.43).

Conclusions

Vitamin B6 could play an important role in PD and its levels seem to be influenced by L-DOPA/CD. Plasma vitamin B6 levels should be monitored in patients receiving high L-DOPA/CD doses, especially those treated with intraduodenal infusion.
In the Kingdom of Triphasic Waves, White Matter Is the Eminence Grise
Authors: Kotchetkov Ivan S. , Freund Brin , Husari Khalil , Kaplan Peter W.
Published: September 2020

Purpose:

Triphasic waves (TWs) have been associated with multiple conditions and adverse outcomes. This study explores the role of white matter disease (WMD) in the generation of TWs when other common causes associated with these discharges are absent.

Methods:

This is a retrospective case series performed at Johns Hopkins Bayview Medical Center from January 2016 to May 2018, which screened for patients with severe WMD, who had TWs on EEG without the presence of commonly cited provoking factors, including (1) hepatic disease; (2) severe uremia over baseline; (3) the drugs cefepime, ifosfamide, lithium, and baclofen; or (4) global hypoxic–ischemic injury. A control population with no WMD or abnormal electrographic findings outside of theta–delta slowing was also identified.

Results:

Eleven patients were identified. The most common comorbid condition was infection, occurring in 82% of patients. Infections were urinary tract infection (36%), respiratory (27%), and central nervous system (18%). Metabolic abnormalities included glucose aberrations (36%), calcium derangements (18%), and hypernatremia (9%). Structural abnormalities included acute stroke (9%) and chronic central nervous system abscess (9%). All except one patient had one or more structural, metabolic, or infectious abnormalities in addition to WMD. Comorbidities were not statistically different in the control population.

Conclusions:

This is the first series to demonstrate convincingly the presence of TWs in patients with WMD in the absence of commonly cited risk factors. The authors hypothesize that less recognized risk factors of WMD and mild metabolic or infectious abnormalities may be drivers of TWs. With a growing elderly population, the presence of WMD will increase, and treating physicians need to look beyond the common causes of TWs.
Group-level patterns emerge from individual speed as revealed by an extremely social robotic fish
Authors: Jolles Jolle W. , Weimar Nils , Landgraf Tim , Romanczuk Pawel , Krause Jens , Bierbach David
Published: September 2020

Understanding the emergence of collective behaviour has long been a key research focus in the natural sciences. Besides the fundamental role of social interaction rules, a combination of theoretical and empirical work indicates individual speed may be a key process that drives the collective behaviour of animal groups. Socially induced changes in speed by interacting animals make it difficult to isolate the effects of individual speed on group-level behaviours. Here, we tackled this issue by pairing guppies with a biomimetic robot. We used a closed-loop tracking and feedback system to let a robotic fish naturally interact with a live partner in real time, and programmed it to strongly copy and follow its partner's movements while lacking any preferred movement speed or directionality of its own. We show that individual differences in guppies' movement speed were highly repeatable and in turn shaped key collective patterns: a higher individual speed resulted in stronger leadership, lower cohesion, higher alignment and better temporal coordination of the pairs. By combining the strengths of individual-based models and observational work with state-of-the-art robotics, we provide novel evidence that individual speed is a key, fundamental process in the emergence of collective behaviour.