bluuebunny/crossref_metadata_2025 huggingface dataset:
Emerging dynamics pathways of response and resistance to PD-1 and CTLA-4 blockade: tackling uncertainty by confronting complexity
Authors: Relecom Allan , Merhi Maysaloun , Inchakalody Varghese , Uddin Shahab , Rinchai Darawan , Bedognetti Davide , Dermime Said
Published: February 2021

Immune checkpoint inhibitors provide considerable therapeutic benefit in a range of solid cancers as well as in a subgroup of hematological malignancies. Response rates are however suboptimal, and despite considerable efforts, predicting response to immune checkpoint inhibitors ahead of their administration in a given patient remains elusive. The study of the dynamics of the immune system and of the tumor under immune checkpoint blockade brought insight into the mechanisms of action of these therapeutic agents. Equally relevant are the mechanisms of adaptive resistance to immune checkpoint inhibitors that have been uncovered through this approach. In this review, we discuss the dynamics of the immune system and of the tumor under immune checkpoint blockade emanating from recent studies on animal models and humans. We will focus on mechanisms of action and of resistance conveying information predictive of therapeutic response.
Is venous blood a more reliable description of acid-base state following simulated hypo- and hyperventilation?
Authors: Shastri Lisha , Kjærgaard Søren , Thyrrestrup Peter S. , Rees Stephen E. , Thomsen Lars P.
Published: February 2021

Background

ABGs are performed in acute conditions as the reference method for assessing the acid-base status of blood. Hyperventilation and breath-holding are common ventilatory changes that occur around the time of sampling, rapidly altering the ‘true’ status of the blood. This is particularly relevant in emergency medicine patients without permanent arterial catheters, where the pain and anxiety of arterial punctures can cause ventilatory changes. This study aimed to determine whether peripheral venous values could be a more reliable measure of blood gases following acute changes in ventilation.

Methods

To allow for characterisation of ventilatory changes typical of acutely ill patients, but without the confounding influence of perfusion or metabolic disturbances, 30 patients scheduled for elective surgery were studied in a prospective observational study. Following anaesthesia, and before the start of the surgery, ventilator settings were altered to achieve a + 100% or − 60% change in alveolar ventilation (‘hyper-’ or ‘hypoventilation’), changes consistent with the anticipation of a painful arterial puncture commonly encountered in the emergency room. Blood samples were drawn simultaneously from indwelling arterial and peripheral venous catheters at baseline, and at 15, 30, 45, 60, 90 and 120 s following the ventilatory change. Comparisons between the timed arterial (or venous) samples were done using repeated-measures ANOVA, with post-hoc analysis using Bonferroni’s correction.

Results

Arterial blood pH and PCO2 changed rapidly within the first 15–30s after both hyper- and hypoventilation, plateauing at around 60s (∆pH = ±0.036 and ∆PCO2 = ±0.64 kPa (4.7 mmHg), respectively), with peripheral venous values remaining relatively constant until 60s, and changing minimally thereafter. Mean arterial changes were significantly different at 30s (P < 0.001) when compared to baseline, in response to both hyper- and hypoventilation.

Conclusion

This study has shown that substantial differences in arterial and peripheral venous acid-base status can be due to acute changes in ventilation, commonly seen in the ER over the 30s necessary to sample arterial blood. If changes are transient, peripheral venous blood may provide a more reliable description of acid-base status.
Echocardiographic parameters during prolonged targeted temperature Management in out-of-hospital Cardiac Arrest Survivors to predict neurological outcome – a post-hoc analysis of the TTH48 trial
Authors: Jensen Thomas Hvid , Juhl-Olsen Peter , Nielsen Bent Roni Ranghøj , Heiberg Johan , Duez Christophe Henri Valdemar , Jeppesen Anni Nørgaard , Frederiksen Christian Alcaraz , Kirkegaard Hans , Grejs Anders Morten
Published: February 2021

Background

Transthoracic echocardiographic (TTE) indices of myocardial function among survivors of out-of-hospital cardiac arrest (OHCA) have been related to neurological outcome; however, results are inconsistent. We hypothesized that changes in average peak systolic mitral annular velocity (s’) from 24 h (h) to 72 h following start of targeted temperature management (TTM) predict six-month neurological outcome in comatose OHCA survivors.

Methods

We investigated the association between peak systolic velocity of the mitral plane (s’) and six-month neurological outcome in a population of 99 patients from a randomised controlled trial comparing TTM at 33 ± 1 °C for 24 h (h) (n = 47) vs. 48 h (n = 52) following OHCA (TTH48-trial). TTE was conducted at 24 h, 48 h, and 72 h after reaching target temperature. The primary outcome was 180 days neurological outcome assessed by Cerebral Performance Category score (CPC180) and the primary TTE outcome measure was s’. Secondary outcome measures were left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), e’, E/e’ and tricuspid annular plane systolic excursion (TAPSE).

Results

Across all three scan time points s’ was not associated with neurological outcome (ORs: 24 h: 1.0 (95%CI: 0.7–1.4, p = 0.98), 48 h: 1.13 (95%CI: 0.9–1.4, p = 0.34), 72 h: 1.04 (95%CI: 0.8–1.4, p = 0.76)). LVEF, GLS, E/e’, and TAPSE recorded on serial TTEs following OHCA were neither associated with nor did they predict CPC180. Estimated median e’ at 48 h following TTM was 5.74 cm/s (95%CI: 5.27–6.22) in patients with good outcome (CPC180 1–2) vs. 4.95 cm/s (95%CI: 4.37–5.54) in patients with poor outcome (CPC180 3–5) (p = 0.04).

Conclusions

s’ assessed on serial TTEs in comatose survivors of OHCA treated with TTM was not associated with CPC180. Our findings suggest that serial TTEs in the early post-resuscitation phase during TTM do not aid the prognostication of neurological outcome following OHCA.

Trial registration

NCT02066753. Registered 14 February 2014 – Retrospectively registered,
Nasal nalbuphine analgesia in prehospital trauma managed by first-responder personnel on ski slopes in Switzerland: an observational cohort study
Authors: Pietsch Urs , Berger Yoël , Schurter David , Theiler Lorenz , Wenzel Volker , Meuli Lorenz , Grünenfelder Andreas , Albrecht Roland
Published: February 2021

Background

Pain is one of the major symptoms complained about by patients in the prehospital setting, especially in the case of trauma. When there is mountainous topography, as in Switzerland, there may be a time delay between injury and arrival of professional rescuers, in particular on ski slopes. Administration of a safe opioid by first responders may improve overall treatment. We therefore assessed administration of nasal nalbuphine as an analgesic treatment for trauma patients in Switzerland.

Methods

This observational cohort study examined 267 patients who were treated with nasal nalbuphine by first responders in six ski resorts in Switzerland. All first responders were instructed to begin treatment by assessing the feasibility of using nalbuphine to treat pain in the patient. A treatment algorithm was developed and distributed to assure that nalbuphine was only administered following a strict protocol. Data regarding pain scores and pain reduction after administration of nalbuphine were collected on-site. Refills were handed out to the first responders with the return of each completed questionnaire.

Results

Nalbuphine provided effective pain relief, with the median level of pain on the numeric rating scale for pain reduced by 3 units on average, from 8 points (p < 0.001). The multivariate regression model showed that pain reduction was more pronounced in patients with higher initial pain levels. Nalbuphine was more effective in adolsecents than in patients aged 20 to 60 years (p = 0.006). No major side effects were observed.

Conclusion

Nasal administration of nalbuphine by first responders is a presumably safe and effective noninvasive pain management strategy for acutely injured patients in the prehospital setting. This may be an alternative, especially in the case of severe pain and prolonged time between arrival of the first responders and arrival of EMS/HEMS personnel on scene.
Enhancing the future of simulation-based education in pediatrics
Authors: Spadea Manuela , Ciantelli Massimiliano , Fossati Nicoletta , Cuttano Armando
Published: February 2021

Technology-enhanced simulation has emerged as a great educational tool for pediatric education. Indeed, it represents an effective method to instruct on technical and non-technical skills, employed by a large number of pediatric training programs. However, this unique pandemic era posed new challenges also on simulation-based education. Beyond the mere facing of the clinical and societal impacts, it is fundamental to take advantage from the current changes and investigate innovative approaches to improve the education of pediatric healthcare professionals. To this aim, we herein lay down the main pillars that should support the infrastructure of the future technology-enhanced simulation.
Epidemiology and microbiology of ventilator-associated pneumonia in COVID-19 patients: a multicenter retrospective study in 188 patients in an un-inundated French region
Authors: Blonz Gauthier , Kouatchet Achille , Chudeau Nicolas , Pontis Emmanuel , Lorber Julien , Lemeur Anthony , Planche Lucie , Lascarrou Jean-Baptiste , Colin Gwenhael
Published: February 2021

Background

The COVID-19 pandemic is responsible for many hospitalizations in intensive care units (ICU), with widespread use of invasive mechanical ventilation (IMV) which exposes patients to the risk of ventilator-associated pneumonia (VAP). The characteristics of VAP in COVID-19 patients remain unclear.

Methods

We retrospectively collected data on all patients hospitalized for COVID-19 during the first phase of the epidemic in one of the seven ICUs of the Pays-de-Loire region (North-West France) and who were on invasive mechanical ventilation for more than 48 h. We studied the characteristics of VAP in these patients. VAP was diagnosed based on official recommendations, and we included only cases of VAP that were confirmed by a quantitative microbiological culture.

Findings

We analyzed data from 188 patients. Of these patients, 48.9% had VAP and 19.7% experienced multiple episodes. Our study showed an incidence of 39.0 VAP per 1000 days of IMV (until the first VAP episode) and an incidence of 33.7 VAP per 1000 days of IMV (including all 141 episodes of VAP). Multi-microbial VAP accounted for 39.0% of all VAP, and 205 pathogens were identified. Enterobacteria accounted for 49.8% of all the isolated pathogens. Bacteremia was associated in 15 (10.6%) cases of VAP. Pneumonia was complicated by thoracic empyema in five cases (3.5%) and by pulmonary abscess in two cases (1.4%). Males were associated with a higher risk of VAP (sHR 2.24 CI95% [1.18; 4.26] p = 0.013).

Interpretation

Our study showed an unusually high incidence of VAP in patients admitted to the ICU for severe COVID-19, even though our services were not inundated during the first wave of the epidemic. We also noted a significant proportion of enterobacteria. VAP-associated complications (abscess, empyema) were not exceptional.

Registration

As an observational study, this study has not been registered.
Addressing uncertainty in genome-scale metabolic model reconstruction and analysis
Authors: Bernstein David B. , Sulheim Snorre , Almaas Eivind , Segrè Daniel
Published: February 2021

The reconstruction and analysis of genome-scale metabolic models constitutes a powerful systems biology approach, with applications ranging from basic understanding of genotype-phenotype mapping to solving biomedical and environmental problems. However, the biological insight obtained from these models is limited by multiple heterogeneous sources of uncertainty, which are often difficult to quantify. Here we review the major sources of uncertainty and survey existing approaches developed for representing and addressing them. A unified formal characterization of these uncertainties through probabilistic approaches and ensemble modeling will facilitate convergence towards consistent reconstruction pipelines, improved data integration algorithms, and more accurate assessment of predictive capacity.
Computer-based alcohol reduction intervention for alcohol-using HIV/HCV co-infected Russian women in clinical care: study protocol for a randomized controlled trial
Authors: DiClemente Ralph J. , Brown Jennifer L. , Capasso Ariadna , Revzina Natalia , Sales Jessica M. , Boeva Ekaterina , Gutova Lyudmila V. , Khalezova Nadia B. , Belyakov Nikolay , Rassokhin Vadim
Published: February 2021

Background

Russia has a high prevalence of human immunodeficiency virus (HIV) infections. In 2018, over one million persons were living with HIV (PLWH); over a third were women. A high proportion of HIV-infected women are co-infected with hepatitis C virus (HCV), and many consume alcohol, which adversely affects HIV and HCV treatment and prognosis. Despite the triple epidemics of alcohol use, HIV and HCV, and the need for interventions to reduce alcohol use among HIV/HCV co-infected women, evidence-based alcohol reduction interventions for this vulnerable population are limited. To address this gap, we developed a clinical trial to evaluate the efficacy of a computer-based intervention to reduce alcohol consumption among HIV/HCV co-infected women in clinical care.

Methods

In this two-arm parallel randomized controlled trial, we propose to evaluate the efficacy of a culturally adapted alcohol reduction intervention delivered via a computer for HIV/HCV co-infected Russian women. The study population consists of women 21–45 years old with confirmed HIV/HCV co-infection who currently use alcohol. Intervention efficacy is assessed by a novel alcohol biomarker, ethyl glucuronide (EtG), and biomarkers of HIV and HCV disease progression. Women are randomized to trial conditions in a 1:1 allocation ratio, using a computer-generated algorithm to develop the assignment sequence and concealment of allocation techniques to minimize assignment bias. Women are randomized to either (1) the computer-based alcohol reduction intervention or (2) the standard-of-care control condition. We will use an intent-to-treat analysis and logistic and linear generalized estimating equations to evaluate intervention efficacy, relative to the standard of care, in enhancing the proportion of women with a laboratory-confirmed negative EtG at each research study visit over the 9-month follow-up period. Additional analyses will evaluate intervention effects on HIV (viral load and CD4+ levels) and HCV markers of disease progression (FibroScan).

Discussion

The proposed trial design and analysis provides an appropriate conceptual and methodological framework to assess the efficacy of the computer-based intervention. We propose to recruit 200 participants.

The intervention, if efficacious, may be an efficient and cost-effective alcohol reduction strategy that is scalable and can be readily disseminated and integrated into clinical care in Russia to reduce women’s alcohol consumption and enhance HIV/HCV prognosis.

Trial registration

ClinicalTrials.gov NCT03362476. Registered on 5 December 2017
Intravenous immunoglobulin and intravenous methylprednisolone as optimal induction treatment in chronic inflammatory demyelinating polyradiculoneuropathy: protocol of an international, randomised, double-blind, placebo-controlled trial (OPTIC)
Authors:   on behalf of the OPTIC study group, Bus S. R. M. , Zambreanu L. , Abbas A. , Rajabally Y. A. , Hadden R. D. M. , de Haan R. J. , de Borgie C. A. J. M. , Lunn M. P. , van Schaik I. N. , Eftimov F.
Published: February 2021

Background

International guidelines recommend either intravenous immunoglobulin (IVIg) or corticosteroids as first-line treatment for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). IVIg treatment usually leads to rapid improvement and is generally safe, but does not seem to lead to long-term remissions. Corticosteroids act more slowly and are associated with more side effects, but may induce long-term remissions. The hypothesis of this study is that combined IVIg and corticosteroid induction treatment will lead to more frequent long-term remissions than IVIg treatment alone.

Methods

An international, randomised, double-blind, placebo-controlled trial, in adults with ‘probable’ or ‘definite’ CIDP according to the EFNS/PNS 2010 criteria. Three groups of patients are included: (1) treatment naïve, (2) known CIDP patients with a relapse after > 1 year without treatment, and (3) patients with CIDP who improved within 3 months after a single course of IVIg, who subsequently deteriorate at any interval without having received additional treatment. Patients are randomised to receive 7 courses of IVIg and 1000 mg intravenous methylprednisolone (IVMP) (in sodium chloride 0.9%) or IVIg and placebo (sodium chloride 0.9%), every 3 weeks for 18 weeks. IVIg treatment consists of a loading dose of 2 g/kg (over 3–5 days) followed by 6 courses of IVIg 1/g/kg (over 1–2 days). The primary outcome is remission at 1 year, defined as improvement in disability from baseline, sustained between week 18 and week 52 without further treatment. Secondary outcomes include changes in disability, impairment, pain, fatigue, quality of life, care use and costs and (long-term) safety.

Discussion

In case of superiority of the combined treatment, patients will experience the advantages of two proven efficacious treatments, namely rapid improvement due to IVIg and long-term remission due to corticosteroids. Long-term remission would reduce the need for maintenance IVIg treatment and may decrease health care costs. Additionally, we expect that the combined treatment leads to a higher proportion of patients with improvement as some patients who do not respond to IVIg will respond to corticosteroids. Risks of short and long-term additional adverse events of the combined treatment need to be assessed.

Trial registration

ISRCTN registry ISRCTN15893334. Prospectively registered on 12 February 2018.
Effects of novel diabetic therapeutic footwear on preventing ulcer recurrence in patients with a history of diabetic foot ulceration: study protocol for an open-label, randomized, controlled trial
Authors: Gao Yun , Wang Chun , Chen Dawei , Huang Hui , Chen Lihong , Liu Guanjian , Lin Shuang , Liu Min , Wen Xiaorong , Cho Jae-Hoon , Chen Yong , Li Yingzhu , Ran Xingwu
Published: February 2021

Background

Recurrence after the healing of a foot ulcer is very common among patients with diabetes mellitus. Novel diabetic therapeutic footwear consisted of merino wool, vibration chip, and orthopedic insoles is designed to influence multifaceted mechanisms of foot ulcer occurrence. The aim of this study is to examine the effect of the optimally designed therapeutic footwear on preventing ulcer recurrence in patients with a history of diabetic foot ulcers (DFU).

Methods/design

The trial is designed as a two arms, parallel-group, open-label randomized controlled intervention study. The Log-rank Test was used for calculating sample size based on the latest national multicenter survey data of DFU in China. Three hundred and twenty participants will be recruited from the Diabetic Foot Care Center, West China Hospital, Sichuan University. Adults with diabetic peripheral neuropathy, healed foot ulceration in the 3 months prior to randomization, and aged ≥18 years, will be recruited. Participants will be randomized to receive novel diabetic therapeutic footwear (n = 160) or their own footwear (n = 160). The primary outcome will be the incidence of ulcer recurrence. The secondary outcome will be measurements of barefoot dynamic plantar pressures, the influence of footwear adherence on ulcer recurrence, and the incidence of cardiovascular events. Assessment visits and data collection will be obtained at baseline, 1, 3, 6, 9, and 12 months. The intention-to-treat principle will be applied. A cox regression model will be used to calculate the hazard ratio for the incidence of ulcer recurrence. The change of barefoot dynamic plantar pressures will be assessed using repeated measures ANOVA. The study protocol has been approved by the Ethics Committee of The Biomedical Research Ethics Committee of West China Hospital, Sichuan University (Reference No. 2019(96)).

Discussion

This clinical trial will give information on the ability of novel diabetic footwear on preventing ulcer recurrence in patients with a history of diabetic foot ulceration. If the optimally designed therapeutic footwear does work well, the findings will contribute to the development of innovative treatment devices for preventing foot ulcer recurrence in high-risk patients.

Trial registration

Chinese Clinical Trial RegistryChiCTR1900025538. Registered on 31 August 2019.
COVID-19 trials: declarations of data sharing intentions at trial registration and at publication
Authors: Li Rebecca , von Isenburg Megan , Levenstein Marcia , Neumann Stan , Wood Julie , Sim Ida
Published: February 2021

Background

The sharing of individual participant-level data from COVID-19 trials would allow re-use and secondary analysis that can help accelerate the identification of effective treatments. The sharing of trial data is not the norm, but the unprecedented pandemic caused by SARS-CoV-2 may serve as an impetus for greater data sharing. We sought to assess the data sharing intentions of interventional COVID-19 trials as declared in trial registrations and publications.

Methods

We searched ClinicalTrials.gov and PubMed for COVID-19 interventional trials. We analyzed responses to ClinicalTrials.gov fields regarding intent to share individual participant level data and analyzed the data sharing statements in eligible publications.

Results

Nine hundred twenty-four trial registrations were analyzed. 15.7% were willing to share, of which 38.6% were willing to share immediately upon publication of results. 47.6% declared they were not willing to share. Twenty-eight publications were analyzed representing 26 unique COVID-19 trials. Only seven publications contained data sharing statements; six indicated a willingness to share data whereas one indicated that data was not available for sharing.

Conclusions

At a time of pressing need for researchers to work together to combat a global pandemic, intent to share individual participant-level data from COVID-19 interventional trials is limited.
Synthesis and therapeutic potential of imidazole containing compounds
Authors: Siwach Ankit , Verma Prabhakar Kumar
Published: February 2021

Imidazole is a five-membered heterocyclic moiety that possesses three carbon, two nitrogen, four hydrogen atoms, and two double bonds. It is also known as 1, 3-diazole. It contains two nitrogen atoms, in which one nitrogen bear a hydrogen atom, and the other is called pyrrole type nitrogen. The imidazole name was reported by Arthur Rudolf Hantzsch (1857–1935) in 1887. 1, 3-diazole is an amphoteric in nature i.e. it shows both acidic and basic properties. It is a white or colorless solid that is highly soluble in water and other polar solvents. Due to the presence of a positive charge on either of two nitrogen atom, it shows two equivalent tautomeric forms. Imidazole was first named glyoxaline because the first synthesis has been made by glyoxal and ammonia. It is the basic core of some natural products such as histidine, purine, histamine and DNA based structures, etc. Among the different heterocyclic compounds, imidazole is better known due to its broad range of chemical and biological properties. Imidazole has become an important synthon in the development of new drugs. The derivatives of 1, 3-diazole show different biological activities such as antibacterial, antimycobacterial, anti-inflammatory, antitumor, antidiabetic, anti-allergic, antipyretic, antiviral, antioxidant, anti-amoebic, antihelmintic, antifungal and ulcerogenic activities, etc. as reported in the literature. There are different examples of commercially available drugs in the market which contains 1, 3-diazole ring such as clemizole (antihistaminic agent), etonitazene (analgesic), enviroxime (antiviral), astemizole (antihistaminic agent), omeprazole, pantoprazole (antiulcer), thiabendazole (antihelmintic), nocodazole (antinematodal), metronidazole, nitroso-imidazole (bactericidal), megazol (trypanocidal), azathioprine (anti rheumatoid arthritis), dacarbazine (Hodgkin's disease), tinidazole, ornidazole (antiprotozoal and antibacterial), etc. This present review summarized some pharmacological activities and various kinds of synthetic routes for imidazole and their derived products.
Applications of intraoperative Duplex ultrasound in vascular surgery: a systematic review
Authors: Normahani Pasha , Khan Bilal , Sounderajah Viknesh , Poushpas Sepideh , Anwar Muzaffar , Jaffer Usman
Published: February 2021

Objective

This review aims to summarise the contemporary uses of intraoperative completion Duplex ultrasound (IODUS) for the assessment of lower extremity bypass surgery (LEB) and carotid artery endarterectomy (CEA).

Methods

We performed a systematic literature search using the databases of MEDLINE. Eligible studies evaluated the use of IODUS during LEB or CEA.

Results

We found 22 eligible studies; 16 considered the use of IODUS in CEA and 6 in LEB. There was considerable heterogeneity between studies in terms of intervention, outcome measures and follow-up. In the assessment of CEA, there is conflicting evidence regarding the benefits of completion imaging. However, analysis from the largest study suggests a modest reduction in adjusted risk of stroke/mortality when using IODUS selectively (RR 0.74, CI 0.63–0.88, p = 0.001). Evidence also suggests that uncorrected residual flow abnormalities detected on IODUS are associated with higher rates of restenosis (range 2.1% to 20%). In the assessment of LEB, we found a paucity of evidence when considering the benefit of IODUS on patency rates or when considering its utility as compared to other imaging modalities. However, the available evidence suggests higher rates of thrombosis or secondary intervention in grafts with uncorrected residual flow abnormalities (up to 36% at 3 months).

Conclusions

IODUS can be used to detect defects in both CEA and LEB procedures. However, there is a need for more robust prospective studies to determine the best scanning strategy, criteria for intervention and the impact on clinical outcomes.
Ultrasound evaluation of the fetal fat tissue, heart, liver and umbilical cord measurements in pregnancies complicated by gestational and type 1 diabetes mellitus: potential application in the fetal birth-weight estimation and prediction of the fetal macrosomia
Authors: Stanirowski Paweł Jan , Majewska Agata , Lipa Michał , Bomba-Opoń Dorota , Wielgoś Mirosław
Published: February 2021

Background

The aim of the study was to evaluate the ultrasound-derived measurements of the fetal soft-tissue, heart, liver and umbilical cord in pregnancies complicated by gestational (GDM) and type 1 diabetes mellitus (T1DM), and further to assess their applicability in the estimation of the fetal birth-weight and prediction of fetal macrosomia.

Methods

Measurements were obtained from diet-controlled GDM (GDMG1) (n = 40), insulin-controlled GDM (GDMG2) (n = 40), T1DM (n = 24) and healthy control (n = 40) patients. The following parameters were selected for analysis: fetal sub-scapular fat mass (SSFM), abdominal fat mass (AFM), mid-thigh fat/lean mass (MTFM/MTLM) and inter-ventricular septum (IVS) thicknesses, heart and thorax circumference and area (HeC/HeA; ThC/ThA), liver length (LL), umbilical cord/vein/arteries circumference and area (UmC/UmA; UvC/UvA; UaC/UaA) together with total umbilical vessels (UveA) and Wharton's jelly area (WjA). Regression models were created in order to assess the contribution of selected parameters to fetal birth-weight (FBW) and risk of fetal macrosomia.

Results

Measurements of the fetal SSFM, AFM, MTFM, MTFM/MTLM ratio, HeC, HeA, IVS, LL, UmC, UmA, UaC, UaA, UveA and WjA were significantly increased among patients with GDMG2/T1DM as compared to GDMG1 and/or control groups (p < .05). The regression analysis revealed that maternal height as well as fetal biparietal diameter, abdominal circumference (AC), AFM and LL measurements were independent predictors of the FBW (p < .05). In addition, increase in the fetal AFM, AC and femur length (FL) was associated with a significant risk of fetal macrosomia occurrence (p < .05). The equation developed for the FBW estimation [FBW(g) = − 2254,942 + 17,204 * FL (mm) + 105,531 * AC (cm) + 131,347 * AFM (mm)] provided significantly lower mean absolute percent error than standard formula in the sub-group of women with T1DM (5.7% vs 9.4%, p < .05). Moreover, new equation including AC, FL and AFM parameters yielded sensitivity of 93.8%, specificity 77.7%, positive predictive value 54.5% and negative predictive value of 97.8% in the prediction of fetal macrosomia.

Conclusions

Ultrasound measurements of the fetal soft tissue, heart, liver and umbilical cord are significantly increased among women with GDM treated with insulin and T1DM. In addition to standard biometric measurements, parameters, such as AFM, may find application in the management of diabetes-complicated pregnancies.
Estimation of energy expenditure of Nordic walking: a crossover trial
Authors: Baek Sora , Ha Yuncheol
Published: February 2021

Background

Nordic walking (NW) requires more energy compared with conventional walking (W). However, the metabolic equation for NW has not been reported. Therefore, this study aimed to characterize responses in oxygen uptake, minute ventilation, heart rate, systolic blood pressure, and surface electromyography of the upper and lower limb muscles during NW and W and develop a metabolic equation for energy expenditure (E, mL·kg− 1·min− 1) of NW.

Methods

This study was performed in a randomized, controlled, crossover design to test the energy expenditure during NW and W. Fifteen healthy young men were enrolled (aged 23.7 ± 3.0 years). All participants performed two randomly ordered walking tests (NW and W) on a treadmill at a predetermined stepwise incremental walking speed (3–5 km·h− 1) and grade (0–7%). The oxygen uptake, minute ventilation, heart rate, systolic blood pressure, and surface electromyography signals of the three upper limb muscles and three lower limb muscles in their right body were recorded and compared between NW and W using paired-t test. Multiple linear regression analysis was used to draw estimation of E during W and NW.

Results

Oxygen uptake (+ 15.8%), minute ventilation (+ 17.0%), heart rate (+ 8.4%), and systolic blood pressure (+ 7.7%) were higher in NW than in W (P < .05). NW resulted in increased muscle activity in all of the upper limb muscles (P < .05). In the lower limb, surface electromyography activities in two of the three lower limb muscles were increased in NW than in W only during level walking (P < .05). Energy expenditure during W and NW was estimated as follows: ENW = 6.1 + 0.09 × speed + 1.19 × speed × grade and EW = 4.4 + 0.09 × speed + 1.20 × speed × grade.

Conclusion

NW showed higher work intensity than W, with an oxygen consumption difference of 1.7 mL·kg− 1·min− 1. The coefficients were not different between the two walking methods. NW involved more muscles of the upper body than W.
Impact of the COVID-19 outbreak on the profession and psychological wellbeing of radiologists: a nationwide online survey
Authors: Coppola Francesca , Faggioni Lorenzo , Neri Emanuele , Grassi Roberto , Miele Vittorio
Published: February 2021

Background

The COVID-19 outbreak has played havoc within healthcare systems, with radiology sharing a substantial burden. Our purpose is to report findings from a survey on the crisis impact among members of the Italian Society of Medical and Interventional Radiology (SIRM).

Methods

All members were invited to a 42-question online survey about the impact of the COVID-19 outbreak on personal and family life, professional activity, socioeconomic and psychological condition. Participants were classified based on working in the most severely affected Italian regions (“hot regions”) or elsewhere.

Results

A total of 2150 radiologists joined the survey. More than 60% of respondents estimated a workload reduction greater than 50%, with a higher prevalence among private workers in hot regions (72.7% vs 66.5% elsewhere, p = 0.1010). Most respondents were concerned that the COVID-19 outbreak could impact the management of non-COVID-19 patients and expected a work overload after the crisis. More than 40% were moderately or severely worried that their professional activity could be damaged, and most residents believed that their training had been affected. More than 50% of respondents had increased emotional stress at work, including moderate or severe symptoms due to sleep disturbances, feeling like living in slow motion and having negative thoughts, those latter being more likely in single-living respondents from hot regions [log OR 0.7108 (CI95% 0.3445 ÷ 1.0770), p = 0.0001].

Conclusions

The COVID-19 outbreak has had a sensible impact on the working and personal life of SIRM members, with more specific criticalities in hot regions. Our findings could aid preserving the radiologists’ wellbeing after the crisis.
Urodynamic effectiveness of a beta-3 adrenoreceptor agonist (vibegron) for a pediatric patient with anticholinergic-resistant neurogenic detrusor overactivity: a case report
Authors: Kato Taiki , Mizuno Kentaro , Nishio Hidenori , Yasui Takahiro , Hayashi Yutaro
Published: February 2021

Background

Myelomeningocele, which causes a neurogenic bladder, is usually treated with anticholinergics in children with neurogenic detrusor overactivity (NDO); however, anticholinergics cause side effects such as dry mouth, constipation, attention deficit, and inadequate reduction in detrusor leak point pressure. Vibegron, a novel selective beta-3 adrenoreceptor agonist, is a well-established alternative to anticholinergics in adults with an overactive bladder. It remains unknown whether this agent can be used for pediatric patients. We report the case of a girl with anticholinergic-resistant NDO due to tethered cord syndrome after myelomeningocele repair, who was treated with vibegron.

Case presentation

A 4-year-old Filipino girl had increased frequency of daytime urinary incontinence and foul-smelling urine since the age of 3. Clinical examination revealed constipation, and urinalysis revealed bacteriuria. Voiding cystourethrography revealed an enlarged and trabeculated bladder without vesicoureteral reflux. On the urodynamic study (UDS), she was found to have detrusor overactivity (DO) and low bladder compliance. She could not void and was diagnosed with overflow incontinence. Clean intermittent catheterization (CIC) and orally administered propiverine (0.8 mg/kg/day) were initiated, and urinary incontinence was resolved. She underwent a UDS annually; the UDS at 6 years of age still revealed DO and low bladder compliance in spite of receiving propiverine. The treatment was switched from propiverine to vibegron (1.4 mg/kg/day). On the UDS after a 5-week treatment schedule of vibegron, the DO disappeared and the bladder compliance improved. CIC and orally administered vibegron have been continued for 7 months so far, and she has had no urinary tract infection with no drug-related adverse events.

Conclusions

Vibegron was effective and well tolerated in the treatment of a pediatric patient with NDO. Vibegron improved the urodynamic parameters for anticholinergic-resistant neurogenic bladder. This agent can be a beneficial and preferable alternative therapeutic agent to anticholinergics in patients with anticholinergic-resistant NDO.
Anti-BCMA CAR T administration in a relapsed and refractory multiple myeloma patient after COVID-19 infection: a case report
Authors: Madduri D. , Parekh S. , Campbell T. B. , Neumann F. , Petrocca F. , Jagannath S.
Published: February 2021

Background

Very little is known about the risk that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection poses to cancer patients, many of whom are immune compromised causing them to be more susceptible to a host of infections. As a precautionary measure, many clinical studies halted enrollment during the initial surge of the global Novel Coronavirus Disease (COVID-19) pandemic. In this case report, we detail the successful treatment of a relapsed and refractory multiple myeloma (MM) patient treated with an anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cell therapy immediately following clinical recovery from COVID-19.

Case presentation

The 57 year old Caucasian male patient had a 4-year history of MM and was considered penta-refractory upon presentation for CAR T cell therapy. He had a history of immunosuppression and received one dose of lymphodepleting chemotherapy (LDC) the day prior to COVID-19 diagnosis; this patient was able to mount a substantial immune response against the SARS-CoV-2 virus, and antiviral antibodies remain detectable 2 months after receiving anti-BCMA CAR T cell therapy. The recent SARS-CoV-2 infection in this patient did not exacerbate CAR T-associated cytokine release syndrome (CRS) and conversely the CAR T cell therapy did not result in COVID-19-related complications. One month after CAR T cell infusion, the patient was assessed to have an unconfirmed partial response per International Myeloma Working Group (IMWG) criteria.

Conclusion

Our case adds important context around treatment choice for MM patients in the era of COVID-19 and whether CAR T therapy can be administered to patients who have recovered from COVID-19. As the COVID-19 global pandemic continues, the decision of whether to proceed with CAR T cell therapy will require extensive discussion weighing the potential risks and benefits of therapy. This case suggests that it is possible to successfully complete anti-BCMA CAR T cell therapy after recovery from COVID-19.

CRB-402 study registered 6 September 2017 at clinicaltrials.gov (NCT03274219).
Symptomatic methemoglobinemia in a patient with metastatic clear cell renal cell carcinoma treated with pembrolizumab and axitinib combination therapy: a case report
Authors: Olsen T. Anders , Martini Dylan J. , Evans Sean T. , Goldman Jamie M. , Bilen Mehmet Asim
Published: February 2021

Background

Combination regimens that include immune checkpoint (ICI) and vascular endothelial growth factor (VEGF) inhibition have opened the door to new treatment opportunities for patients with metastatic renal cell carcinoma (mRCC). While these treatment options have provided improved tolerability and better outcomes compared to older regimens, many patients still experience a myriad of treatment-related adverse events. Given that these regimens were recently approved for mRCC, the complete side effect profile may not be fully elucidated yet.

Case presentation

We report a case of a 73-year old White male with mRCC who was managed with an ICI-VEGF inhibitor combination regimen. He experienced a partial response (Fig. 1) but had side effects including symptomatic cyanosis diagnosed as methemoglobinemia which led to treatment discontinuation. Upon holding his therapy, his methemoglobinemia and cyanosis resolved.

Conclusions

Combination VEGF-ICI therapy provide novel regimens for advanced solid tumor malignancies including mRCC. While shown to have improved efficacy in clinical trials, it is crucial that oncologists uncover the full side effect profile of these novel agents especially as their use becomes more standard in the management of advanced malignancies. To our knowledge, this is the first reported case of a patient experiencing symptomatic methemoglobinemia as an adverse event associated with a VEGF-ICI combination regimen. While the cause of this side effect is unclear, in this paper we attempt to elucidate a process that is in line with the mechanism of action of these therapies to explain how these agents, specifically the axitinib, could have caused the methemoglobin to rise to a symptomatic level.
Respiratory depression in a neonate born to mother on maximum dose sertraline: a case report
Authors: Marchand Greg J. , Meassick Katerina , Wolf Hannah , Hopewell Sophia K. , Sainz Katelyn , Anderson Sienna M. , Ware Kelly , Vallejo Janelle , King Alexa , Ruther Stacy , Brazil Giovanna , Cieminski Kaitlynne , Calteux Nicolas
Published: February 2021

Background

Mood and anxiety disorders are common in women of childbearing age, especially during the peripartum period. As more women seek medical management for these conditions, there is an increasing need for studies to better examine the effects of exposure to selective serotonin reuptake inhibitors (SSRIs), and other antidepressants, on newborns at the time of delivery.

Case presentation

We report the case of a term Caucasian infant born to a 17-year-old white female taking 100 mg of sertraline daily for depression and anxiety who exhibited respiratory depression and hypoxia after an uncomplicated vaginal delivery. The neonate was treated with the use of continuous positive airway pressure (CPAP) and supplemental oxygen and subsequently the symptoms resolved without complication.

Conclusions

We present this case with the suspicion of poor neonatal adjustment syndrome as the possible cause of the respiratory depression and hypoxia in this newborn.
Metastatic ovarian cancer spreading into mammary ducts mimicking an in situ component of primary breast cancer: a case report
Authors: Maeshima Yurina , Osako Tomo , Morizono Hidetomo , Yunokawa Mayu , Miyagi Yumi , Kikuchi Mari , Ueno Takayuki , Ohno Shinji , Akiyama Futoshi
Published: February 2021

Background

Accurate diagnosis of metastatic tumors in the breast is crucial because the therapeutic approach is essentially different from primary tumors. A key morphological feature of metastatic tumors is their lack of anin situcarcinoma component. Here, we present a unique case of metastatic ovarian carcinoma spreading into mammary ducts and mimicked anin situcomponent of primary carcinoma. To our knowledge, this is the second case (and the first adult case) confirming thein situ-mimicking growth pattern of a metastatic tumor using immunohistochemistry.

Case presentation

A 69-year-old Japanese woman was found to have a breast mass with microcalcifications. She had a known history of ovarian mixed serous and endocervical-type mucinous (seromucinous) carcinoma. Needle biopsy specimen of the breast tumor revealed adenocarcinoma displaying anin situ-looking tubular architecture in addition to invasive micropapillary and papillary architectures with psammoma bodies. From these morphological features, metastatic serous carcinoma and invasive micropapillary carcinoma of breast origin were both suspected. In immunohistochemistry, the cancer cells were immunoreactive for WT1, PAX8, and CA125, and negative for GATA3, mammaglobin, and gross cystic disease fluid protein-15. Therefore, the breast tumor was diagnosed to be metastatic ovarian serous carcinoma. Thein situ-looking architecture showed the same immunophenotype, but was surrounded by myoepithelium confirmed by immunohistochemistry (e.g. p63, cytokeratin 14, CD10). Thus, the histogenesis of thein situ-like tubular foci was could be explained by the spread of metastatic ovarian cancer cells into existing mammary ducts.

Conclusion

Metastatic tumors may spread into mammary duct units and mimic anin situcarcinoma component of primary breast cancer. Thisin situ-mimicking growth pattern can be a potential pitfall in establishing a correct diagnosis of metastasis to the breast. A panel of breast-related and extramammary organ/tumor-specific immunohistochemical markers may be helpful in distinguishing metastatic tumors from primary tumors.
Estimating Fisher discriminant error in a linear integrator model of neural population activity
Authors: Calderini Matias , Thivierge Jean-Philippe
Published: February 2021

Decoding approaches provide a useful means of estimating the information contained in neuronal circuits. In this work, we analyze the expected classification error of a decoder based on Fisher linear discriminant analysis. We provide expressions that relate decoding error to the specific parameters of a population model that performs linear integration of sensory input. Results show conditions that lead to beneficial and detrimental effects of noise correlation on decoding. Further, the proposed framework sheds light on the contribution of neuronal noise, highlighting cases where, counter-intuitively, increased noise may lead to improved decoding performance. Finally, we examined the impact of dynamical parameters, including neuronal leak and integration time constant, on decoding. Overall, this work presents a fruitful approach to the study of decoding using a comprehensive theoretical framework that merges dynamical parameters with estimates of readout error.
Telemedical emergency services: central or decentral coordination?
Authors: Fleßa Steffen , Suess Rebekka , Kuntosch Julia , Krohn Markus , Metelmann Bibiana , Hasebrook Joachim Paul , Brinkrolf Peter , Hahnenkamp Klaus , Kohnen Dorothea , Metelmann Camilla
Published: February 2021

Background and objective

Teleemergency doctors support ambulance cars at the emergency site by means of telemedicine. Currently, each district has its own teleemergency doctor office (decentralized solution). This paper analyses the advantages and disadvantages of a centralized solution where several teleemergency doctors work in parallel in one office to support the ambulances in more districts.

Methods

The service of incoming calls from ambulances to the teleemergency doctor office can be modelled as a queuing system. Based on the data of the district of Vorpommern-Greifswald in the Northeast of Germany, we assume that arrivals and services are Markov chains. The model has parallel channels proportionate to the number of teleemergency doctors working simultaneously and the number of calls which one doctor can handle in parallel. We develop a cost function with variable, fixed and step-fixed costs.

Results

For the district of Greifswald, the likelihood that an incoming call has to be put on hold because the teleemergency doctor is already fully occupied is negligible. Centralization of several districts with a higher number of ambulances in one teleemergency doctor office will increase the likelihood of overburdening and require more doctors working simultaneously. The cost of the teleemergency doctor office per ambulance serviced strongly declines with the number of districts cooperating.

Discussion

The calculations indicate that centralization is feasible and cost-effective. Other advantages (e.g. improved quality, higher flexibility) and disadvantages (lack of knowledge of the location and infrastructure) of centralization are discussed.

Conclusions

We recommend centralization of telemedical emergency services. However, the number of districts cooperating in one teleemergency doctor office should not be too high and the distance between the ambulance station and the telemedical station should not be too large.