bluuebunny/crossref_metadata_2025 huggingface dataset:
A systematic review on clinical effectiveness, side-effect profile and meta-analysis on continuation rate of etonogestrel contraceptive implant
Authors: Moray Kusum V. , Chaurasia Himanshu , Sachin Oshima , Joshi Beena
Published: January 2021

Background

Unintended pregnancies (UIP) have a significant impact on health of women and the health budget of countries. Contraception is an effective way to prevent UIPs. The study objective was to collate evidence on clinical effectiveness of etonogestrel subdermal implant (ESI), continuation rate and side effect profile among eligible women of reproductive age group, as compared to levonorgestrel intrauterine system (LNG-IUS), copper intrauterine device (Cu-IUD) and depot medroxy progesterone acetate injections; other types of contraceptive implants were excluded as comparators.

Methods

The protocol of the systematic review was registered in Prospero (registration number: CRD42018116580). MEDLINE via PubMed, Cochrane library and web of science were the electronic databases searched. A search strategy was formulated and studies from 1998 to 2019 were included. Clinical trial registries and grey literature search was done. Critical assessment of included studies was done using appropriate tools. A qualitative synthesis of included studies was done and a meta-analysis was conducted in RevMan software for continuation rates of ESI as compared to other long acting reversible contraceptives (LARC) e.g. LNG IUS and Cu-IUD.

Results

The search yielded 23,545 studies. After excluding 467 duplicates, 23,078 titles were screened and 51 studies were included for the review. Eight of the 15 studies reporting clinical effectiveness reported 100% effectiveness and overall pearl index ranged from 0 to 1.4. One-year continuation rates ranged from 57–97%; 44–95% at the end of second year and 25–78% by 3 years of use. Abnormal menstruation was the most commonly reported side effect. There was no significant difference in bone mineral density at 1 year follow-up. The meta-analyses showed that odds ratio (OR) of 1-year continuation rate was 1.55 (1.36, 1.76) for LNG-IUS vs. ESI and 1.34 (1.13, 1.58) for copper-IUD vs. ESI; showing that continuation rates at the end of one-year were higher in LNG-IUS and copper-IUD as compared to ESI.

Conclusion

ESI is clinically effective and safe contraceptive method to use, yet 1-year continuation rates are lower as compared to LNG-IUS and copper-IUD, mostly attributed to the disturbances in the menstruation.
User-centred assistive SystEm for arm Functions in neUromuscuLar subjects (USEFUL): a randomized controlled study
Authors: Longatelli Valeria , Antonietti Alberto , Biffi Emilia , Diella Eleonora , D’Angelo Maria Grazia , Rossini Mauro , Molteni Franco , Bocciolone Marco , Pedrocchi Alessandra , Gandolla Marta
Published: January 2021

Background

Upper limb assistive devices can compensate for muscular weakness and empower the user in the execution of daily activities. Multiple devices have been recently proposed but there is still a lack in the scientific comparison of their efficacy.

Methods

We conducted a cross-over multi-centric randomized controlled trial to assess the functional improvement at the upper limb level of two arms supports on 36 patients with muscular dystrophy. Participants tested a passive device (i.e., Wrex by Jaeco) and a semi-active solution for gravity compensation (i.e., Armon Ayura). We evaluated devices’ effectiveness with an externally-assessed scale (i.e., Performance of the Upper Limb-PUL-module), a self-perceived scale (i.e., Abilhand questionnaire), and a usability scale (i.e., System Usability Scale). Friedman’s test was used to assess significant functional gain for PUL module and Abilhand questionnaire. Moreover, PUL changes were compared by means of the Friedman’s test.

Results

Most of the patients improved upper limb function with the use of arm supports (median PUL scores increase of 1–3 points). However, the effectiveness of each device was related to the level of residual ability of the end-user. Slightly impaired patients maintained the same independence without and with assistive devices, even if they reported reduced muscular fatigue for both devices. Moderately impaired patients enhanced their arm functionality with both devices, and they obtained higher improvements with the semi-active one (median PUL scores increase of 9 points). Finally, severely impaired subjects benefited only from the semi-active device (median PUL scores increase of 12 points). Inadequate strength was recognized as a barrier to passive devices. The usability, measured by the System Usability Scale, was evaluated by end-users “good” (70/100 points) for the passive, and “excellent” (80/100 points) for the semi-active device.

Conclusions

This study demonstrated that assistive devices can improve the quality of life of people suffering from muscular dystrophy. The use of passive devices, despite being low cost and easy to use, shows limitations in the efficacy of the assistance to daily tasks, limiting the assistance to a predefined horizontal plane. The addition of one active degree of freedom improves efficacy and usability especially for medium to severe patients. Further investigations are needed to increase the evidence on the effect of arm supports on quality of life and diseases’ progression in subjects with degenerative disorders.

Trial registration clinicaltrials.gov, NCT03127241, Registered 25th April 2017. The clinical trial was also registered as a post-market study at the Italian Ministry of Health.
Characterization of four virulent Klebsiella pneumoniae bacteriophages, and evaluation of their potential use in complex phage preparation
Authors: Zurabov Fedor , Zhilenkov Evgeniy
Published: January 2021

Background

Nowadays, hundreds of thousands of deaths per year are caused by antibiotic resistant nosocomial infections and the prognosis for future years is much worse, as evidenced by modern research. Bacteria of theKlebsiellagenus are one of the main pathogens that cause nosocomial infections. Among the many antimicrobials offered to replace or supplement traditional antibiotics, bacteriophages are promising candidates.

Methods

This article presents microbiological, physicochemical and genomic characterization of 4 virulent bacteriophages belonging toSiphoviridae,MyoviridaeandPodoviridaefamilies. Phages were studied by electron microscopy; their host range, lytic activity, adsorption rate, burst size, latent period, frequency of phage-resistant forms generation, lysis dynamics and sensitivity of phage particles to temperature and pH were identified; genomes of all 4 bacteriophages were studied by restriction digestion and complete genome sequence.

Results

Studied phages showed wide host range and high stability at different temperature and pH values. In contrast with single phages, a cocktail of bacteriophages lysed all studied bacterial strains, moreover, no cases of the emergence of phage-resistant bacterial colonies were detected. Genomic data proved that isolated viruses do not carry antibiotic resistance, virulence or lysogenic genes. Three out of four bacteriophages encode polysaccharide depolymerases, which are involved in the degradation of biofilms and capsules.

Conclusions

The bacteriophages studied in this work are promising for further in vivo studies and might be used in phage therapy as part of a complex therapeutic and prophylactic phage preparation. The conducted studies showed that the complex preparation is more effective than individual phages. The use of the complex phage cocktail allows to extend the lytic spectrum, and significantly reduces the possibility of phage-resistant forms generation.
Understanding factors affecting breastfeeding practices in one city in the Kingdom of Saudi Arabia: an interpretative phenomenological study
Authors: Murad Amal , Renfrew Mary J. , Symon Andrew , Whitford Heather
Published: January 2021

Background

Breastfeeding duration has declined in the Kingdom of Saudi Arabia (KSA) in recent decades, although accurate national data about different breastfeeding indicators by infant age are lacking. This qualitative study, the first in KSA, aimed to understand the factors affecting mothers’ decisions and experiences regarding any breastfeeding practices.

Methods

A qualitative phenomenological approach was used to investigate mothers’ experiences of breastfeeding. Non-probability convenience sampling and snowballing strategies were designed to recruit participants. Semi-structured interviews were conducted with 16 mothers, from two hospitals and three primary health clinics in Al-Madinah city, from December 2017 to March 2018. Interpretative phenomenological analysis was the analysis framework.

Results

Three themes were identified: 1) ‘Up against the system’: policies, staff and systems were the main barriers to exclusive breastfeeding; 2) ‘Social support and negativity’: family support in the first 40 postpartum days protected breastfeeding continuation and was highly appreciated, but negative comments limited breastfeeding practices thereafter; and 3) ‘Managing tensions’: mothers’ religious beliefs about breastfeeding boosted their decisions; however, the challenge of managing tensions influenced mothers to stop breastfeeding earlier than they wished. The study revealed that mothers had no doubts about wanting to breastfeed their babies; but continuation was adversely affected by unhelpful hospital policies and staff actions, the lack of ongoing social support, and by others people’s negativity, rather than by the mothers’ own views. Stopping breastfeeding earlier than planned was a complex decision for most mothers. However, mothers said that they intended to breastfeed their next baby successfully.

Conclusions

Healthcare professionals (maternity staff, paediatricians and pharmacists) need education and training to support exclusive breastfeeding effectively. Increasing the number of hospitals with Baby Friendly Hospital Initiative accreditation, which includes staff practice changes, is needed to protect and support exclusive breastfeeding. Ongoing professional and peer support, and improving conditions at workplaces and universities, are needed to help mothers to continue breastfeeding successfully. Effective, coordinated national policies can support mothers’ decisions in relation to breastfeeding. Such changes will reduce the tensions experienced by women and help them to achieve their breastfeeding goals and to breastfeed for longer.
Duration of breastfeeding, age at introduction of complementary foods and allergy-related diseases: a prospective cohort study
Authors: Ekelund Louise , Gloppen Inga , Øien Torbjørn , Simpson Melanie Rae
Published: January 2021

Background

The influences of breastfeeding and infant diet in the prevention of allergy-related diseases are uncertain and many of the studies conducted on the topic are limited by methodological challenges. Our aim was to assess whether the duration of breastfeeding and age at complementary food introduction affected the prevalence of asthma, wheeze, allergic rhinoconjunctivitis (ARC) and eczema at two and six years of age.

Methods

We used information gathered between 2000 and 2014 through questionnaires in the Prevention of Allergy among Children in Trondheim (PACT) study, a prospective cohort study in Trondheim, Norway. The current study includes 6802 children who submitted questionnaires detailing breastfeeding duration and or age at introduction to complementary foods, as well as at least one of the child health questionnaires completed at two and six years of age. Adjusted odds ratios (aORs) were calculated for each combination of exposure and outcomes and sensitivity analyses were performed to assess the possible influence of recall bias and reverse causality.

Results

The mean duration of breastfeeding was 11 months (SD 5.6) in this study population and 5695 of 6796 (84%) infants had been breastfed for at least 6 months. We did not find any conclusive preventative effect of longer breastfeeding on parental reported doctor-diagnosed asthma, aOR 0.79 (95% CI 0.51, 1.21). However, at 6 years of age we observed a reduction in the less strictly defined outcome wheeze, aOR 0.71 (95% CI 0.53, 0.95). Longer breastfeeding was associated with a reduced risk of ARC at 2 years, aOR 0.65 (95% CI 0.49, 0.86), with a continued protective trend at 6 years, aOR 0.77 (95% CI 0.58, 1.04).

Conclusions

Longer breastfeeding resulted in a reduced risk of wheeze and a trend towards a protective effect on ARC up until school age. No conclusive associations were seen between the duration of breastfeeding or age at introduction to complementary foods and prevention of asthma, wheeze, ARC and eczema.

Trial registration

The trial is registered in Current Controlled Trials as ISRCTN28090297.
Improving the sorting efficiency of maize haploid kernels using an NMR-based method with oil content double thresholds
Authors: Qu Yanzhi , Liu Zonghua , Zhang Yazhou , Yang Jiwei , Li Haochuan
Published: January 2021

Background

Maize haploid breeding technology can be used to rapidly develop homozygous lines, significantly shorten the breeding cycle and improve breeding efficiency. Rapid and accurate sorting haploid kernels is a prerequisite for the large-scale application of this technology. At present, the automatic haploid sorting based on nuclear magnetic resonance (NMR) using a single threshold method has been realized. However, embryo-aborted (EmA) kernels are usually produced during in vivo haploid induction, and both haploids and EmA kernels have lower oil content and are separated together using a single threshold method based on NMR. This leads to a higher haploid false discrimination rate (FDR) and requires secondary manual sorting to select the haploid kernels from the mixtures, which increases the sorting cost and decreases the haploid sorting efficiency. In order to improve the correct discrimination rate (CDR) in sorting haploids, a method to distinguish EmA kernels is required.

Results

Single kernel weight and oil content were measured for the diploid, haploid, and EmA kernels derived from three maize hybrids and nine inbred lines by in vivo induction. The results showed that the distribution of oil content showed defined boundaries between the three types of kernels, while the single kernel weight didn't. According to the distribution of oil content in the three types of kernels, a double-threshold method was proposed to distinguish the embryo-aborted kernels, haploid and diploid kernels based on NMR and their oil content. The double thresholds were set based on the minimum oil content of diploid kernels and the maximum content of EmA kernels as the upper and lower boundary values, respectively. The CDR of EmA kernels in different maize materials was > 97.8%, and the average FDR was reduced by 27.9 percent.

Conclusions

The oil content is an appropriate indicator to discriminate diploid, haploid and EmA kernels. An oil content double-threshold method based on NMR was first developed in this study to identify the three types of kernels. This methodology could reduce the FDR of haploids and improve the sorting efficiency of automated sorting system. Thus, this technique represents a potentially efficient method for haploid sorting and provides a reference for the process of automated sorting of haploid kernels with high efficiency using NMR.
Metastasis directed stereotactic radiotherapy in NSCLC patients progressing under targeted- or immunotherapy: efficacy and safety reporting from the ‘TOaSTT’ database
Authors: Kroeze Stephanie G. C. , Schaule Jana , Fritz Corinna , Kaul David , Blanck Oliver , Kahl Klaus H. , Roeder Falk , Siva Shankar , Verhoeff Joost J. C. , Adebahr Sonja , Schymalla Markus M. , Glatzer Markus , Szuecs Marcella , Geier Michael , Skazikis Georgios , Sackerer Irina , Lohaus Fabian , Eckert Franziska , Guckenberger Matthias
Published: January 2021

Background

Metastasis directed treatment (MDT) is increasingly performed with the attempt to improve outcome in non-small cell lung cancer (NSCLC) patients receiving targeted- or immunotherapy (TT/IT). This study aimed to assess the safety and efficacy of metastasis directed stereotactic radiotherapy (SRT) concurrent to TT/IT in NSCLC patients.

Methods

A retrospective multicenter cohort of stage IV NSCLC patients treated with TT/IT and concurrent (≤ 30 days) MDT was established. 56% and 44% of patients were treated for oligoprogressive disease (OPD) or polyprogressive disease (PPD) under TT/IT, polyprogressive respectively. Survival was analyzed using Kaplan–Meier and log rank testing. Toxicity was scored using CTCAE v4.03 criteria. Predictive factors for overall survival (OS), progression free survival (PFS) and time to therapy switch (TTS) were analyzed with uni- and multivariate analysis.

Results

MDT of 192 lesions in 108 patients was performed between 07/2009 and 05/2018. Concurrent TT/IT consisted of EGFR/ALK-inhibitors (60%), immune checkpoint inhibitors (31%), VEGF-antibodies (8%) and PARP-inhibitors (1%). 2y-OS was 51% for OPD and 25% for PPD. After 1 year, 58% of OPD and 39% of PPD patients remained on the same TT/IT. Second progression after MDT was oligometastatic (≤ 5 lesions) in 59% of patients. Severe acute and late toxicity was observed in 5.5% and 1.9% of patients. In multivariate analysis, OS was influenced by the clinical metastatic status (p = 0.002, HR 2.03, 95% CI 1.30–3.17). PFS was better in patients receiving their first line of systemic treatment (p = 0.033, HR 1.7, 95% CI 1.05–2.77) and with only one metastases-affected organ (p = 0.023, HR 2.04, 95% CI 1.10–3.79). TTS was 6 months longer in patients with one metastases-affected organ (p = 0.031, HR 2.53, 95% CI 1.09–5.89). Death was never therapy-related.

Conclusions

Metastases-directed SRT in NSCLC patients can be safely performed concurrent to TT/IT with a low risk of severe toxicity. To find the ideal sequence of the available multidisciplinary treatment options for NSCLC and determine what patients will benefit most, a further evaluated in a broader context within prospective clinical trials is needed continuation of TT/IT beyond progression combined with MDT for progressive lesions appears promising but requires prospective evaluation.

Trial registration: retrospectively registered
Global metabolomic and lipidomic analysis reveals the potential mechanisms of hemolysis effect of Ophiopogonin D and Ophiopogonin D' in vivo
Authors: Xu Huan-Hua , Jiang Zhen-Hong , Huang Cong-Shu , Sun Yu-Ting , Xu Long-Long , Tang Xiang-Ling , Tan Hong-Ling , Ma Zeng-Chun , Gao Yue
Published: January 2021

Background

OPD and OPD' are the two main active components of Ophiopogon japonicas in Shenmai injection (SMI). Being isomers of each other, they are supposed to have similar pharmacological activities, but the actual situation is complicated. The difference of hemolytic behavior between OPD and OPD' in vivo and in vitro was discovered and reported by our group for the first time. In vitro, only OPD' showed hemolysis reaction, while in vivo, both OPD and OPD' caused hemolysis. In vitro, the primary cause of hemolysis has been confirmed to be related to the difference between physical and chemical properties of OPD and OPD'. In vivo, although there is a possible explanation for this phenomenon, the one is that OPD is bio-transformed into OPD' or its analogues in vivo, the other one is that both OPD and OPD' were metabolized into more activated forms for hemolysis. However, the mechanism of hemolysis in vivo is still unclear, especially the existing literature are still difficult to explain why OPD shows the inconsistent hemolysis behavior in vivo and in vitro. Therefore, the study of hemolysis of OPD and OPD' in vivo is of great practical significance in response to the increase of adverse events of SMI.

Methods

Aiming at the hemolysis in vivo, this manuscript adopted untargeted metabolomics and lipidomics technology to preliminarily explore the changes of plasma metabolites and lipids of OPD- and OPD'-treated rats. Metabolomics and lipidomics analyses were performed on ultra-high performance liquid chromatography (UPLC) system tandem with different mass spectrometers (MS) and different columns respectively. Multivariate statistical approaches such as principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA) were applied to screen the differential metabolites and lipids.

Results

Both OPD and OPD' groups experienced hemolysis, Changes in endogenous differential metabolites and differential lipids, enrichment of differential metabolic pathways, and correlation analysis of differential metabolites and lipids all indicated that the causes of hemolysis by OPD and OPD' were closely related to the interference of phospholipid metabolism.

Conclusions

This study provided a comprehensive description of metabolomics and lipidomics changes between OPD- and OPD'-treated rats, it would add to the knowledge base of the field, which also provided scientific guidance for the subsequent mechanism research. However, the underlying mechanism require further research.
Patient’s thoughts and expectations about centres of expertise for PKU
Authors: van Wegberg A. M. J. , MacDonald A. , Abeln D. , Hagedorn T. S. , Lange E. , Trefz F. , van Vliet D. , van Spronsen F. J.
Published: January 2021

Background

In the Netherlands (NL) the government assigned 2 hospitals as centres of expertise (CE) for Phenylketonuria (PKU), while in the United Kingdom (UK) and Germany no centres are assigned specifically as PKU CE’s.

Methods

To identify expectations of patients/caregivers with PKU of CEs, a web-based survey was distributed through the national Phenylketonuria societies of Germany, NL and UK.

Results

In total, 105 responded (43 patients, 56 parents, 4 grandparents, 2 other) of whom 59 were from NL, 33 from UK and 13 from Germany. All participants (n = 105) agreed that patients and/or practitioners would benefit from CEs. The frequency patients would want to visit a CE, when not treated in a CE (n = 83) varied: every hospital visit (24%, n = 20), annual or bi-annual (45%, n = 37), at defined patient ages (6%, n = 5), one visit only (22%, n = 18), or never (4%, n = 3). Distance was reported as a major barrier (42%, n = 35). 78% (n = 65) expected CE physicians and dieticians to have a higher level of knowledge than in non-CE centres. For participants already treated in a CE (n = 68), 66% requested a more extensive annual or bi-annual review. In general, psychology review and neuropsychologist assessment were identified as necessary by approximately half of the 105 participants. In addition, 66% (n = 68) expected a strong collaboration with patient associations.

Conclusion

In this small study, most participants expected that assigning CEs will change the structure of and delivery of Phenylketonuria care.
Quality of life in Italian patients with Multiple endocrine neoplasia type 1 (MEN 1): results of an extensive survey
Authors: Giusti Francesca , Cioppi Federica , Fossi Caterina , Marini Francesca , Masi Laura , Tonelli Francesco , Brandi Maria Luisa
Published: January 2021

Background

MEN1 is a complex, rare, syndrome inherited in an autosomal dominant tract and characterized by the development of multiple neuroendocrine tumors, requiring lifelong surveillance and multiple medical and surgical therapies throughout the patient’s life. For all these reasons, a diagnosis of MEN1 can be a psychological shock for the patient, as well as his/her relatives, more so than the diagnosis of a single tumor. In the last two decades, clinicians have started to consider the emotional, psychological, relational, and social aspects of their patients’ lives. The data collected in the present analyses highlight the unique features of MEN1 syndrome, and aim to evaluate the Quality of Life in the patients and their relatives. In this study, a comprehensive survey of various aspects of Health-Related Quality of Life was performed in a large series of Italian MEN1 patients, by administering five of the most common targeted questionnaires.

Results

The results of the study showed that our patients, despite having a complex multi-tumor syndrome, were moderately optimistic (50%), and this corresponds with a normal Quality of Life. This positive response is strictly correlated with the fact that the patients are cared for at a dedicated Referral Center, receiving personalized care and constant follow-up, which gives them reassurance regarding the high quality of management of the disorder.

Conclusions

The possibility of having access to a clinical Referral Center for their complex rare disease, together with the support of a dedicated patient association, has been demonstrated to be the ideal model for the management of post-diagnosis shock, and contributes to the preservation of a good Health-Related Quality of Life for MEN1 patients.
Primary lymphedema French National Diagnosis and Care Protocol (PNDS; Protocole National de Diagnostic et de Soins)
Authors:   French National Referral Center for Primary Lymphedema, Vignes Stéphane , Albuisson Juliette , Champion Laurence , Constans Joël , Tauveron Valérie , Malloizel Julie , Quéré Isabelle , Simon Laura , Arrault Maria , Trévidic Patrick , Azria Philippe , Maruani Annabel
Published: January 2021

Primary lymphedema is a rare chronic pathology associated with constitutional abnormalities of the lymphatic system. The objective of this French National Diagnosis and Care Protocol (Protocole National de Diagnostic et de Soins; PNDS), based on a critical literature review and multidisciplinary expert consensus, is to provide health professionals with an explanation of the optimal management and care of patients with primary lymphedema. This PNDS, written by consultants at the French National Referral Center for Primary Lymphedema, was published in 2019 (https://has-sante.fr/upload/docs/application/pdf/2019-02/pnds_lymphoedeme_primaire_final_has.pdf).
Primary lymphedema can be isolated or syndromic (whose manifestations are more complex with a group of symptoms) and mainly affects the lower limbs, or, much more rarely, upper limbs or external genitalia. Women are more frequently affected than men, preferentially young. The diagnosis is clinical, associating mild or non-pitting edema and skin thickening, as confirmed by the Stemmer’s sign (impossibility to pinch the skin on the dorsal side or the base of the second toe), which is pathognomonic of lymphedema. Limb lymphoscintigraphy is useful to confirm the diagnosis. Other causes of swelling or edema of the lower limbs must be ruled out, such as lipedema. The main acute lymphedema complication is cellulitis (erysipelas). Functional and psychological repercussions can be major,
deteriorating the patient’s quality of life. Treatment aims to prevent those complications, reduce the volume with low-stretch bandages, then stabilize it over the long term by exercises and wearing a compression garment. Patient education (or parents of a child) is essential to improve observance.
RMRP, RMST, FTX and IPW: novel potential long non-coding RNAs in medullary thyroid cancer
Authors: Luzón-Toro Berta , Villalba-Benito Leticia , Fernández Raquel María , Torroglosa Ana , Antiñolo Guillermo , Borrego Salud
Published: January 2021

The relevant role of long non-coding RNAs (lncRNAs) in cancer is currently a matter of increasing interest. Medullary thyroid cancer (MTC) is a rare neuroendocrine tumor (2–5% of all thyroid cancer) derived from the parafollicular C-cells which secrete calcitonin. About 75% of all medullary thyroid cancers are believed to be sporadic medullary thyroid cancer (sMTC), whereas the remaining 25% correspond to inherited cancer syndromes known as Multiple Endocrine Neoplasia type 2 (MEN2). MEN2 syndrome, with autosomal dominant inheritance is caused by germline gain of function mutations in RET proto-oncogene. To date no lncRNA has been associated to MEN2 syndrome and only two articles have been published relating long non-coding RNA (lncRNA) to MTC: the first one linked MALAT1 with sMTC and, in the other, our group determined some new lncRNAs in a small group of sMTC cases in fresh tissue (RMST, FTX, IPW, PRNCR1, ADAMTS9-AS2 and RMRP). The aim of the current study is to validate such novel lncRNAs previously described by our group by using a larger cohort of patients, in order to discern their potential role in the disease. Here we have tested three up-regulated (RMST, FTX, IPW) and one down-regulated (RMRP) lncRNAs in our samples (formalin fixed paraffin embedded tissues from twenty-one MEN2 and ten sMTC patients) by RT-qPCR analysis. The preliminary results reinforce the potential role of RMST, FTX, IPW and RMRP in the pathogenesis of MTC.
Current challenges and controversies in the management of scapular fractures: a review
Authors: Pires Robinson Esteves , Giordano Vincenzo , de Souza Felipe Serrão Mendes , Labronici Pedro José
Published: January 2021

Fractures of the scapula are rare and usually associated with high-energy trauma. The unfavorable scapular anatomy, combined with the complexity of the approaches for fracture fixation, make the treatment challenging, even for experienced surgeons. Furthermore, the literature is controversial regarding surgical indications and rationale for treatment. The present review article was designed to address and discuss critical aspects of decision-making for the management of scapular fractures, including surgical indications and patient safety considerations.
Vulnerability to low-dose combination of irinotecan and niraparib in ATM-mutated colorectal cancer
Authors: Vitiello Pietro Paolo , Martini Giulia , Mele Luigi , Giunta Emilio Francesco , De Falco Vincenzo , Ciardiello Davide , Belli Valentina , Cardone Claudia , Matrone Nunzia , Poliero Luca , Tirino Virginia , Napolitano Stefania , Della Corte Carminia , Selvaggi Francesco , Papaccio Gianpaolo , Troiani Teresa , Morgillo Floriana , Desiderio Vincenzo , Ciardiello Fortunato , Martinelli Erika
Published: January 2021

Background

Despite the advancements in new therapies for colorectal cancer (CRC), chemotherapy still constitutes the mainstay of the medical treatment. For this reason, new strategies to increase the efficacy of chemotherapy are desirable. Poly-ADP-Ribose Polymerase inhibitors (PARPi) have shown to increase the activity of DNA damaging chemotherapeutics used in the treatment of CRC, however previous clinical trials failed to validate these results and pointed out dose-limiting toxicities that hamper the use of such combinations in unselected CRC patients. Nevertheless, in these studies little attention was paid to the mutational status of homologous recombination repair (HRR) genes.

Methods

We tested the combination of the PARPi niraparib with either 5-fluorouracil, oxaliplatin or irinotecan (SN38) in a panel of 12 molecularly annotated CRC cell lines, encompassing the 4 consensus molecular subtypes (CMSs). Synergism was calculated using the Chou-Talalay method for drug interaction. A correlation between synergism and genetic alterations in genes involved in homologous recombination (HR) repair was performed. We used clonogenic assays, mice xenograft models and patient-derived 3D spheroids to validate the results. The induction of DNA damage was studied by immunofluorescence.

Results

We showed that human CRC cell lines, as well as patient-derived 3D spheroids, harboring pathogenic ATM mutations are significantly vulnerable to PARPi/chemotherapy combination at low doses, regardless of consensus molecular subtypes (CMS) and microsatellite status. The strongest synergism was shown for the combination of niraparib with irinotecan, and the presence of ATM mutations was associated to a delay in the resolution of double strand breaks (DSBs) through HRR and DNA damage persistence.

Conclusions

This work demonstrates that a numerically relevant subset of CRCs carrying heterozygous ATM mutations may benefit from the combination treatment with low doses of niraparib and irinotecan, suggesting a new potential approach in the treatment of ATM-mutated CRC, that deserves to be prospectively validated in clinical trials.
Behaviour change approaches for individuals with diabetes to improve foot self‐management: a scoping review
Authors: Paton Joanne , Abey Sally , Hendy Phil , Williams Jennifer , Collings Richard , Callaghan Lynne
Published: January 2021

Background

Diabetes related foot complications are increasing in complexity, frequency and cost. The application of self‐management strategies can reduce the risk of individuals developing foot complications. The type, range and nature of the literature focusing on interventions that support patients with diabetic foot self‐management is unknown. This scoping review aimed to i) identify self‐management actions and risky behaviour avoidance strategies within interventions, ii) map the theoretical functions through which these behaviour change interventions have an effect, iii) display gaps in the research.

Methodology

Arksey and Malley's (2003) 5 stage framework was followed to conduct the scoping study. This methodological framework was selected because it was developed specifically for scoping reviews and therefore offered clear methodological distinction from systematic review methodology..

Databases were searched from inception of the project until June 2020 supplemented by hand searching of reference lists. In total 988 papers were identified. These were independently screened by three reviewers, identifying 19 eligible papers. Data extraction and charting of data was independently conducted by three reviewers to identify study characteristics, self‐management actions and risky behaviours. Data was charted against the COM‐B (capability, opportunity, motivation, behaviour) model of behaviour to determine intervention function.

Results

In total 25 different foot self‐management actions and risk behaviours were classified into three themes; routine self‐management, trauma avoidance and warning signs and actions. Inspect feet daily received the most attention. The majority of interventions focused on knowledge and skills, but overlooked taking action and decision making. Intervention mapping identified four primary intervention functions (education, persuasion, training and enablement) used to address deficits in capability, opportunity and motivation that positively improved foot self‐management behaviour. No studies targeted first ulcer prevention, and most either did not measure or improve foot health outcomes.

Conclusion

This review charted the evidence for interventions promoting diabetic foot self‐management through a theoretical behaviour change perspective. A core set of behaviour change activities and intervention functions associated with positive changes in behaviour were identified. This information will provide researchers with a useful basis for developing self‐management interventions.
The protective effects of phosphodiesterase-5 inhibitor, sildenafil on post-resuscitation cardiac dysfunction of cardiac arrest: by regulating the miR-155-5p and miR-145-5p
Authors: He Yong , Wang Guoxing , Li Chuang , Wang Yuxing , Zhang Qian
Published: January 2021

Background

MiRNA-155 and miRNA-145 have been demonstrated to function as a key regulator in the development of the cardiovascular system. Recent experimental and clinical studies have indicated the cardioprotective role of sildenafil during ischemia/reperfusion (I/R) injury. This study was designed to investigate if administration of sildenafil will attenuate post-resuscitation myocardial dysfunction by regulating miRNA-155 and miR-145 expressions.

Methods

Thirty-two male pigs (weighing 30 ± 2 kg) were randomly divided into 4 groups, sildenafil group (n = 8), sildenafil +NG-nitro-l-arginine methyl ester (L-NAME) (20 mg/kg L) group (n = 8), saline (SA group, n = 8); and sham operation group (sham group, n = 8). Eight minutes of untreated VF was followed by defibrillation in anesthetized, closed-chest pigs. Hemodynamic status and blood samples were obtained at 0 min, 0.5, 1, 2, 4 and 6 h after return of spontaneous circulation (ROSC), and the hearts were removed and analyzed under electron microscopy, quantitative real-time polymerase chain reaction and ultra structural analysis were performed to evaluate myocardial injury.

Results

Compared with the sildenafil + L-NAME and saline groups, the sildenafil group had better outcomes in terms of hemodynamic and oxygen metabolism parameters as well as 24-h survival rate, and attenuated myocardial injury; In this study, CA pigs showed evidently increased levels of miR-155-5p and miR-145-5p, while the sildenafil treatment decreased the levels of miR-155-5p and miR-145-5p in CA pigs. In addition, the levels of eNOS was decreased in CA pigs, validating sildenafil attenuating post-resuscitation myocardial dysfunction by regulating miRNA-155 and miR-145 expressions.

Conclusions

Sildenafil group had better outcomes in terms of hemodynamic and oxygen metabolism parameters as well as 24-h survival rate, inhibited the increases in the miR-155-5p and miR-145-5p levels and attenuated myocardial injury in a porcine model of CA and resuscitation.
Alternatives to direct emergency department conveyance of ambulance patients: a scoping review of the evidence
Authors: Blodgett Joanna M. , Robertson Duncan J. , Pennington Elspeth , Ratcliffe David , Rockwood Kenneth
Published: January 2021

Background

The role of ambulance services is shifting, due in part to more intermediate, non-urgent patients who do not require direct emergency department conveyance, yet who cannot be safely left at home alone. Evidence surrounding the safety, effectiveness and efficiency of alternate care routes is not well known.

Methods

This scoping review sought to identify all studies that examined alternate routes of care for the non-urgent “intermediate” patient, as triaged on scene. Search terms for the sample (ambulances, paramedics, etc.) and intervention (e.g. referrals, alternate care route, non-conveyance) were combined. Articles were systematically searched using four databases and grey literature sources (February 2020). Independent researchers screened title-abstract and full text stages.

Results

Of 16,037 records, 41 examined alternate routes of care after triage by the on-scene paramedic. Eighteen articles considered quantitative patient data, 12 studies provided qualitative perspectives while 11 were consensus or opinion-based articles. The benefits of alternative schemes are well-recognised by patients, paramedics and stakeholders and there is supporting evidence for a positive impact on patient-centered care and operational efficiency. Challenges to successful use of schemes included: patient safety resulting from incorrect triage decisions, inadequate training, lack of formal partnerships between ambulance and supporting services, and insufficient evidence to support safe implementation or continued use. Studies often inaccurately defined success using proxies for patient safety (e.g. decision comparisons, rates of secondary contact). Finally, patients expressed willingness for such schemes but their preference must be better understood.

Conclusions

This broad summary offers initial support for alternate routes of care for intermediate, non-urgent patients. Even so, most studies lacked methodologically rigorous evidence and failed to evaluate safe patient outcomes. Some remedies appear to be available such as formal triage pathways, targeted training and organisational support, however there is an urgent need for more research and dissemination in this area.
Hospital-level intracranial pressure monitoring utilization and functional outcome in severe traumatic brain injury: a post hoc analysis of prospective multicenter observational study
Authors: Okazaki Tomoya , Kawakita Kenya , Kuroda Yasuhiro
Published: January 2021

Background

Several observational studies have shown that hospital-level intracranial pressure (ICP) monitoring utilization varies considerably in patients with severe traumatic brain injury (TBI). However, the relationship between hospital-level ICP monitoring utilization and clinical functional outcomes is unknown. This study examined whether patients with severe TBI treated at hospitals with high ICP monitoring utilization have better functional outcomes.

Methods

A post hoc analysis of the data from a prospective multicenter cohort study in Japan was undertaken, and included severe TBI patients (Glasgow Come Scale score ≤ 8). The primary exposure was hospital-level ICP monitoring utilization. Patients treated at hospitals with more than 80% ICP monitoring utilization were assigned to a high group and the others to a low group. The primary endpoint was a favorable functional outcome at 6 months after injury, defined as a Glasgow Outcome Scale score of good recovery or moderate disability. We conducted multiple logistic regression analyses adjusted for potential confounders.

Results

Of the 427 included patients, 60 were assigned to the high group and 367 to the low group. Multiple logistic regression analysis revealed that patients in the high group had significantly better functional outcome (adjusted odds ratio [OR]: 2.36; 95% confidence interval [CI]: 1.17–4.76; p = 0.016). Multiple logistic regression analysis adjusted for additional confounders supported this result (adjusted OR: 2.30; 95% CI: 1.07–4.92; p = 0.033).

Conclusion

Treatment at hospitals with high ICP monitoring utilization for severe TBI patients could be associated with better functional outcome.
Efficacy of repetitive transcranial magnetic stimulation combined with visual scanning treatment on cognitive and behavioral symptoms of left hemispatial neglect in right hemispheric stroke patients: study protocol for a randomized controlled trial
Authors: Di Gregorio Francesco , La Porta Fabio , Casanova Emanuela , Magni Elisabetta , Bonora Roberta , Ercolino Maria Grazia , Petrone Valeria , Leo Maria Rosaria , Piperno Roberto
Published: January 2021

Background

Left hemispatial neglect (LHN) is a neuropsychological syndrome often associated with right hemispheric stroke. Patients with LHN have difficulties in attending, responding, and consciously representing the right side of space. Various rehabilitation protocols have been proposed to reduce clinical symptoms related to LHN, using cognitive treatments, or on non-invasive brain stimulation. However, evidence of their benefit is still lacking; in particular, only a few studies focused on the efficacy of combining different approaches in the same patient.

Methods

In the present study, we present the SMART ATLAS trial (StimolazioneMAgneticaRipetitivaTranscranica nell’ATtenzioneLAteralizzata dopoStroke), a multicenter, randomized, controlled trial with pre-test (baseline), post-test, and 12 weeks follow-up assessments based on a novel rehabilitation protocol based on the combination of brain stimulation and standard cognitive treatment. In particular, we will compare the efficacy of inhibitory repetitive-transcranial magnetic stimulation (r-TMS), applied over the left intact parietal cortex of LHN patients, followed by visual scanning treatment, in comparison with a placebo stimulation (SHAM control) followed by the same visual scanning treatment, on visuospatial symptoms and neurophysiological parameters of LHN in a population of stroke patients.

Discussion

Our trial results may provide scientific evidence of a new, relatively low-cost rehabilitation protocol for the treatment of LHN.

Trial registration

ClinicalTrials.govNCT04080999. Registered on September 2019.
Exercise therapy and patient education versus intra-articular saline injections in the treatment of knee osteoarthritis: an evidence-based protocol for an open-label randomised controlled trial (the DISCO trial)
Authors: Bandak Elisabeth , Overgaard Anders F. , Kristensen Lars Erik , Ellegaard Karen , Guldberg-Møller Jørgen , Bartholdy Cecilie , Hunter David J. , Altman Roy D. , Christensen Robin , Bliddal Henning , Henriksen Marius
Published: January 2021

Background

Knee osteoarthritis (OA) is a highly prevalent musculoskeletal condition causing pain, physical disability, and reduced quality of life. Exercise and patient education are non-pharmacological interventions for knee OA unanimously recommended as first-line treatments based on extensive research evidence. However, none of the numerous randomised controlled trials of exercise and education for knee OA has used adequate sham/placebo comparison groups because the ‘active’ ingredients are unknown. Designing and executing an adequate and ‘blindable placebo’ version of an exercise and education intervention is impossible. Therefore, using an open-label study design, this trial compares the efficacy of a widely used ‘state-of-art’ exercise and education intervention (Good Life with osteoarthritis in Denmark; GLAD) with presumably inert intra-articular saline injections on improvement in knee pain in patients with knee OA.

Methods

In this open-label randomised trial, we will include 200 patients with radiographically verified OA of the knee and randomly allocate them to one of two interventions: (i) 8 weeks of exercise and education (GLAD) or (ii) Intra-articular injections of 5 ml isotonic saline every second week for a total of 4 injections. Outcomes are taken at baseline, after 8 weeks of treatment (week 9; primary endpoint) and after an additional 4 weeks of follow-up (week 12). The primary outcome is change from baseline in the Knee Injury and Osteoarthritis Outcome Score questionnaire (KOOS) pain subscale score. Secondary outcomes include the Physical function in Activities of Daily Living, Symptoms, and Knee-related Quality of Life subscales of the KOOS, the patients’ global assessment of disease impact, physical performance tests, and presence of knee joint swelling.

Discussion

This current trial compares a presumably active treatment (GLAD) with a presumably inert treatment (IA saline injections). Both study interventions have well-established and anticipated similar effects on knee OA symptoms, but the underlying mechanisms are unknown. The interpretation of the results of this trial will likely be difficult and controversial but will contribute to a better understanding of the bias introduced in the effect estimation of classically unblindable exercise and education interventions for knee OA.

Trial registration

www.ClinicalTrials.govNCT03843931. Prospectively registered on 18 February 2019.