bluuebunny/crossref_metadata_2025 huggingface dataset:
Phenotypic characterization of X-linked hypophosphatemia in pediatric Spanish population
Authors: Rodríguez-Rubio Enrique , Gil-Peña Helena , Chocron Sara , Madariaga Leire , de la Cerda-Ojeda Francisco , Fernández-Fernández Marta , de Lucas-Collantes Carmen , Gil Marta , Luis-Yanes María Isabel , Vergara Inés , González-Rodríguez Juan David , Ferrando Susana , Antón-Gamero Montserrat , Carrasco Hidalgo-Barquero Marta , Fernández-Escribano Angustias , Fernández-Maseda Mº Ángeles , Espinosa Laura , Oliet Aniana , Vicente Antonio , Ariceta Gema , Santos Fernando ,   RenalTubeGroup
Published: February 2021

Background

X-linked hypophosphatemia (XLH) is a hereditary rare disease caused by loss-of-function mutations in PHEX gene leading tohypophosphatemia and high renal loss of phosphate. Rickets and growth retardation are the major manifestations of XLH in children, but there is a broad phenotypic variability. Few publications have reported large series of patients. Current data on the clinical spectrum of the disease, the correlation with the underlying gene mutations, and the long-term outcome of patients on conventional treatment are needed, particularly because of the recent availability of new specific medications to treat XLH.

Results

The RenalTube database was used to retrospectively analyze 48 Spanish patients (15 men) from 39 different families, ranging from 3 months to 8 years and 2 months of age at the time of diagnosis (median age of 2.0 years), and with XLH confirmed by genetic analysis. Bone deformities, radiological signs of active rickets and growth retardation were the most common findings at diagnosis. Mean (± SEM) height was − 1.89 ± 0.19 SDS and 55% (22/40) of patients had height SDS below—2. All cases had hypophosphatemia, serum phosphate being − 2.81 ± 0.11 SDS. Clinical manifestations and severity of the disease were similar in both genders. No genotype—phenotype correlation was found. Conventional treatment did not attenuate growth retardation after a median follow up of 7.42 years (IQR = 11.26; n = 26 patients) and failed to normalize serum concentrations of phosphate. Eleven patients had mild hyperparathyroidism and 8 patients nephrocalcinosis.

Conclusions

This study shows that growth retardation and rickets were the most prevalent clinical manifestations at diagnosis in a large series of Spanish pediatric patients with XLH confirmed by mutations in the PHEX gene. Traditional treatment with phosphate and vitamin D supplements did not improve height or corrected hypophosphatemia and was associated with a risk of hyperparathyroidism and nephrocalcinosis. The severity of the disease was similar in males and females.
Impact of single and combined rare diseases on adult inpatient outcomes: a retrospective, cross-sectional study of a large inpatient population
Authors: Blazsik Reka Maria , Beeler Patrick Emanuel , Tarcak Karol , Cheetham Marcus , von Wyl Viktor , Dressel Holger
Published: February 2021

Background

Little is known about the impact of rare diseases on inpatient outcomes.

Objective

To compare outcomes of inpatients with 0, 1, or > 1 rare disease. A catalogue of 628 ICD-10 coded rare diseases was applied to count rare diseases.

Design

Retrospective, cross-sectional study.

Subjects

165,908 inpatients, Swiss teaching hospital.

Main measures

Primary outcome: in-hospital mortality. Secondary outcomes: length of stay (LOS), intensive care unit (ICU) admissions, ICU LOS, and 30-day readmissions. Associations with single and combined rare diseases were analyzed by multivariable regression.

Key results

Patients with 1 rare disease were at increased risk of in-hospital death (odds ratio [OR]: 1.80; 95% confidence interval [CI]: 1.67, 1.95), combinations of rare diseases showed stronger associations (OR 2.78; 95% CI 2.39, 3.23). Females with 1 rare disease had an OR of 1.69 (95% CI 1.50, 1.91) for in-hospital death, an OR of 2.99 (95% CI 2.36, 3.79) if they had a combination of rare diseases. Males had an OR of 1.85 (95% CI 1.68, 2.04) and 2.61 (95% CI 2.15, 3.16), respectively. Rare diseases were associated with longer LOS (for 1 and > 1 rare diseases: increase by 28 and 49%), ICU admissions (for 1 and > 1: OR 1.64 [95% CI 1.57, 1.71] and 2.23 [95% CI 2.01, 2.48]), longer ICU LOS (for 1 and > 1 rare diseases: increase by 14 and 40%), and 30-day readmissions (for 1 and > 1: OR 1.57 [95% CI 1.47, 1.68] and 1.64 [95% CI 1.37, 1.96]).

Conclusions

Rare diseases are independently associated with worse inpatient outcomes. This might be the first study suggesting even stronger associations of combined rare diseases with in-hospital deaths, increased LOS, ICU admissions, increased ICU LOS, and 30-day readmissions.
Changes in PCSK 9 and apolipoprotein B100 in Niemann–Pick disease after enzyme replacement therapy with olipudase alfa
Authors: Garside Bethanie , Ho Jan Hoong , Kwok See , Liu Yifen , Dhage Shaishav , Donn Rachelle , Iqbal Zohaib , Jones Simon A. , Soran Handrean
Published: February 2021

Background

Enzyme replacement therapy (ERT) with olipudase alfa, a recombinant human acid sphingomyelinase (rhASM), is being developed to treat patients with ASM deficiency (ASMD), commonly known as Niemann–Pick disease (NPD) types A or B. This study assessed the effect of ERT on lipid parameters and inflammatory markers.

Methods

Serum and plasma samples from five adults with NPD type B (NPD-B) who received olipudase alfa ERT for 26 weeks were analysed. We also collected fasting blood samples from fifteen age- and sex-matched participants as reference and comparison group. We measured fasting lipid profile, apolipoproteins B48 and B100 (apoB48 and apoB100), apolipoprotein A1 (apoA1), proprotein convertase subtilisin/klexin type 9 (PCSK9) mass, oxidised low-density lipoprotein (oxLDL), small dense low-density lipoprotein cholesterol (sdLDL-C) and tumour necrosis factor α (TNF-α).

Results

Patients with NPD-B, compared with age and sex matched reference group, had higher triglycerides, PCSK9, apoB48, oxLDL and TNF-α and lower high density lipoprotein cholesterol (HDL-C) and apoA1. Treatment with ERT was associated with improved lipid parameters including total cholesterol, triglycerides, low density lipoprotein cholesterol (LDL-C), sdLDL-C, oxLDL and apoB100. Though there was an increase in apoA1, HDL-C was slightly reduced. TNF-α showed a reduction. ApoB100 decreased in parallel with a decrease in total serum PCSK9 mass after ERT.

Conclusion

This study demonstrated that patients with NPD-B had a proatherogenic lipid profile and higher circulating TNF-α compared to reference group. There was an improvement in dyslipidaemia after olipudase alfa. It was possible that reductions in LDL-C and apoB100 were driven by reductions in TNF-α and PCSK9 following ERT.
A deleterious mutation in the ALMS1 gene in a naturally occurring model of hypertrophic cardiomyopathy in the Sphynx cat
Authors: Meurs Kathryn M. , Williams Brian G. , DeProspero Dylan , Friedenberg Steven G. , Malarkey David E. , Ezzell J. Ashley , Keene Bruce W. , Adin Darcy B. , DeFrancesco Teresa C. , Tou Sandra
Published: February 2021

Background

Familial hypertrophic cardiomyopathy is a common inherited cardiovascular disorder in people. Many causal mutations have been identified, but about 40% of cases do not have a known causative mutation. Mutations in the ALMS1 gene are associated with the development of Alstrom syndrome, a multisystem familial disease that can include cardiomyopathy (dilated, restrictive). Hypertrophic cardiomyopathy has not been described. The ALMS1 gene is a large gene that encodes for a ubiquitously expressed protein. The function of the protein is not well understood although it is believed to be associated with energy metabolism and homeostasis, cell differentiation and cell cycle control. The ALMS1 protein has also been shown to be involved in the regulation of cell cycle proliferation in perinatal cardiomyocytes. Although cardiomyocyte cell division and replication in mammals generally declines soon after birth, inhibition of ALMS1 expression in mice lead to increased cardiomyocyte proliferation, and deficiency of Alstrom protein has been suggested to impair post-natal cardiomyocyte cell cycle arrest. Here we describe the association of familial hypertrophic cardiomyopathy in Sphynx cats with a novel ALMS1 mutation.

Results

A G/C variant was identified in exon 12 (human exon 13) of the ALMS1 gene in affected cats and was positively associated with the presence of hypertrophic cardiomyopathy in the feline population (p < 0.0001). The variant was predicted to change a highly conserved nonpolar Glycine to a positively charged Arginine. This was predicted to be a deleterious change by three in silico programs. Protein prediction programs indicated that the variant changed the protein structure in this region from a coil to a helix. Light microscopy findings included myofiber disarray with interstitial fibrosis with significantly more nuclear proliferative activity in the affected cats than controls (p < 0.0001).

Conclusion

This study demonstrates a novel form of cardiomyopathy associated with ALMS1 in the cat. Familial hypertrophic cardiomyopathy is a disease of genetic heterogeneity; many of the known causative genes encoding for sarcomeric proteins. Our findings suggest that variants in genes involved with cardiac development and cell regulation, like the ALMS1 gene, may deserve further consideration for association with familial hypertrophic cardiomyopathy.
Clinical experience with the AKT1 inhibitor miransertib in two children with PIK3CA-related overgrowth syndrome
Authors: Forde Karina , Resta Nicoletta , Ranieri Carlotta , Rea David , Kubassova Olga , Hinton Mark , Andrews Katrina A. , Semple Robert , Irvine Alan D. , Dvorakova Veronika
Published: February 2021

Background

PIK3CA-related overgrowth spectrum (PROS) refers to a group of rare disorders, caused by somatic activating mutations in PIK3CA, resulting in abnormal PI3K-AKT-mTOR pathway signalling. Significant associated morbidity is frequently observed, and approved treatments are lacking. Miransertib (ARQ 092) is a novel, orally available, selective pan-AKT inhibitor with proven in vitro efficacy. Following recent results of the use of AKT inhibitors in Proteus syndrome (PS) and AKT-mutant cancers, we investigated its therapeutic use in two patients with severe PROS who had exhausted conventional treatment methods.

Results

Two patients, one with CLOVES variant (P1) and one with facial infiltrating lipomatosis and hemimegalencephaly (P2), were commenced on miransertib treatment on a compassionate use basis. In patient one, intra-abdominal and paraspinal overgrowth had resulted in respiratory compromise, obstructive uropathy, dysfunctional seating and lying postures, and chronic pain. In patient two, hemifacial overgrowth and hemimegalencephaly had caused difficulties with articulation and oral function, and refractory epilepsy. Miransertib treatment was continued for a median duration of 22 months (range 22–28). In patient one, alleviation of respiratory compromise was observed and functionally, seating and lying postures improved. Serial volumetric MRI analysis revealed 15% reduction in calculated volumes of fatty overgrowth between treatment commencement and end. In patient two, reduction in seizure burden and improved parent-reported quality of life measures were reported. Treatment was discontinued in both patients due to lack of sustained response, and poor compliance in year two of treatment (P2). No significant toxicities were reported.

Conclusion

We report the first paediatric case series of the use of miransertib in two children with PROS. Objective clinical response was observed in patient one, and improvement in key qualitative outcomes was reported in patient two. Treatment was well tolerated with no significant toxicities reported. This case series highlights the potential therapeutic utility of miransertib in selected paediatric patients with severe PROS, and further demonstrates the potential for re-purposing targeted therapies for the treatment of rare diseases. An open label, Phase 1/2 study of miransertib in children with PROS and PS is underway to more accurately assess the efficacy of miransertib in the treatment of PROS disorder (NCT03094832).
Lessons from a theory of change-driven evaluation of a global mental health funding portfolio
Authors: Esponda G. Miguel , Ryan G. K. , Estrin G. Lockwood , Usmani S. , Lee L. , Murphy J. , Qureshi O. , Endale T. , Regan M. , Eaton J. , De Silva M.
Published: February 2021

Background

Given the underinvestment in global mental health to-date, it is important to consider how best to maximize the impact of existing investments. Theory of Change (ToC) is increasingly attracting the interest of funders seeking to evaluate their own impact. This is one of four papers investigating Grand Challenges Canada’s (GCC’s) first global mental health research funding portfolio (2012–2016) using a ToC-driven approach.

Methods

A portfolio-level ToC map was developed through a collaborative process involving GCC grantees and other key stakeholders. Proposed ToC indicators were harmonised with GCC’s pre-existing Results-based Management and Accountability Framework to produce a “Core Metrics Framework” of 23 indicators linked to 17 outcomes of the ToC map. For each indicator relevant to their project, the grantee was asked to set a target prior to the start of implementation, then report results at six-month intervals. We used the latest available dataset from all 56 projects in GCC’s global mental health funding portfolio to produce a descriptive analysis of projects’ characteristics and outcomes related to delivery.

Results

12,999 people were trained to provide services, the majority of whom were lay or other non-specialist health workers. Most projects exceeded their training targets for capacity-building, except for those training lay health workers. Of the 321,933 people screened by GCC-funded projects, 162,915 received treatment. Most projects focused on more than one disorder and exceeded all their targets for screening, diagnosis and treatment. Fewer people than intended were screened for common mental disorders and epilepsy (60% and 54%, respectively), but many more were diagnosed and treated than originally proposed (148% and 174%, respectively). In contrast, the three projects that focused on perinatal depression exceeded screening and diagnosis targets, but only treated 43% of their intended target.

Conclusions

Under- or over-achievement of targets may reflect operational challenges such as high staff turnover, or challenges in setting appropriate targets, for example due to insufficient epidemiological evidence. Differences in delivery outcomes when disaggregated by disorder suggest that these challenges are not universal. We caution implementers, funders and evaluators from taking a one-size-fits all approach and make several recommendations for how to facilitate more in-depth, multi-method evaluation of impact using portfolio-level ToC.
The mental health impact of COVID-19 outbreak: a Nationwide Survey in Iran
Authors: Shahriarirad Reza , Erfani Amirhossein , Ranjbar Keivan , Bazrafshan Amir , Mirahmadizadeh Alireza
Published: February 2021

Background

Disease outbreak not only carries the risk of death to the public due to the infection, but it also can lead to unbearable psychological impact on the mental health of the individuals. This study aims to explore and evaluate the burden of psychological problems on the Iranian general population during the outbreak of COVID-19.

Method

A cross-sectional web-based survey was conducted among the general population of Iran age 15 and above. Demographic variables, depression, and anxiety symptoms were evaluated using the Patient Health Questionnaire-9 and General Anxiety Disorder-7 questionnaires.

Results

Among the 8591 participants, the mean age was 34.37 (± 11.25) years and 66.4% were female while 33.6% were male. Based on our results, 1295 (15.1%) and 1733 (20.1%) of the general population had clinically significant depressive and anxiety symptoms, respectively. Based on the demographic variables, female gender was associated with a higher risk for developing depression and anxiety symptoms, whereas getting information about the disease from medical journals and articles, being older, and being married were considered as associated protective factors. In terms of depression, being a healthcare worker was an associated risk factor. On the other hand, for anxiety, having higher education was a protective factor while a higher number of individuals in a household was considered as a risk factor.

Conclusions

This study identified a major mental health problem in the Iranian population during the time of the COVID-19 outbreak. Therefore, establishing a targeted mental health support program during the time of public emergencies, such as the disease outbreak, is advised.
Correction to: Viral time capsule: a global photo‑elicitation study of child and adolescent mental health professionals during COVID‑19
Authors: Herrington Olivia D. , Clayton Ashley , Benoit Laelia , Prins-Aardema Cecil , DiGiovanni Madeline , Weller Indigo , Martin Andrés
Published: February 2021

An amendment to this paper has been published and can be accessed via the original article.
COVID-19 vaccines for patients with cancer: benefits likely outweigh risks
Authors: Hwang Joyce K. , Zhang Tian , Wang Andrew Z. , Li Zihai
Published: February 2021

Less than a year since the start of the COVID-19 pandemic, ten vaccines against SARS-CoV-2 have been approved for at least limited use, with over sixty others in clinical trials. This swift achievement has generated excitement and arrives at a time of great need, as the number of COVID-19 cases worldwide continues to rapidly increase. Two vaccines are currently approved for full use, both built on mRNA and lipid nanotechnology platforms, a success story of mRNA technology 20 years in the making. For patients with cancer, questions arise around the safety and efficacy of these vaccines in the setting of immune alterations engendered by their malignancy and/or therapies. We summarize the current data on leading COVID-19 vaccine candidates and vaccination of patients undergoing immunomodulatory cancer treatments. Most current cancer therapeutics should not prevent the generation of protective immunity. We call for more research in this area and recommend that the majority of patients with cancer receive COVID vaccinations when possible.
Watchful waiting as a strategy to reduce low-value spinal imaging: study protocol for a randomized trial
Authors: Fenton Joshua J. , Jerant Anthony , Franks Peter , Gosdin Melissa , Fridman Ilona , Cipri Camille , Weinberg Gary , Hudnut Andrew , Tancredi Daniel J.
Published: February 2021

Background

Patients with acute low back pain frequently request diagnostic imaging, and clinicians feel pressure to acquiesce to such requests to sustain patient trust and satisfaction. Spinal imaging in patients with acute low back pain poses risks from diagnostic evaluation of false-positive findings, patient labeling and anxiety, and unnecessary treatment (including spinal surgery). Watchful waiting advice has been an effective strategy to reduce some low-value treatments, and some evidence suggests a watchful waiting approach would be acceptable to many patients requesting diagnostic tests.

Methods

We will use key informant interviews of clinicians and focus groups with primary care patients to refine a theory-informed standardized patient-based intervention designed to teach clinicians how to advise watchful waiting when patients request low-value spinal imaging for low back pain. We will test the effectiveness of the intervention in a randomized clinical trial. We will recruit 8–10 primary care and urgent care clinics (~ 55 clinicians) in Sacramento, CA; clinicians will be randomized 1:1 to intervention and control groups. Over a 3- to 6-month period, clinicians in the intervention group will receive 3 visits with standardized patient instructors (SPIs) portraying patients with acute back pain; SPIs will instruct clinicians in a three-step model emphasizing establishing trust, empathic communication, and negotiation of a watchful waiting approach. Control physicians will receive no intervention. The primary outcome is the post-intervention rate of spinal imaging among actual patients with acute back pain seen by the clinicians adjusted for rate of imaging during a baseline period. Secondary outcomes are use of targeted communication techniques during a follow-up visit with an SP, clinician self-reported use of watchful waiting with actual low back pain patients, post-intervention rates of diagnostic imaging for other musculoskeletal pain syndromes (to test for generalization of intervention effects beyond back pain), and patient trust and satisfaction with physicians.

Discussion

This trial will determine whether standardized patient instructors can help clinicians develop skill in negotiating a watchful waiting approach with patients with acute low back pain, thereby reducing rates of low-value spinal imaging. The trial will also examine the possibility that intervention effects generalize to other diagnostic tests.

Trial registration

ClinicalTrials.govNCT 04255199. Registered on January 20, 2020
Increased expression of fatty acid and ABC transporters enhances seed oil production in camelina
Authors: Cai Guangqin , Wang Geliang , Kim Sang-Chul , Li Jianwu , Zhou Yongming , Wang Xuemin
Published: February 2021

Background

Lipid transporters play an essential role in lipid delivery and distribution, but their influence on seed oil production in oilseed crops is not well studied.

Results

Here, we examined the effect of two lipid transporters,FAX1(fatty acid export1) andABCA9(ATP-binding cassette transporter subfamily A9) on oil production and lipid metabolism in the oilseed plantCamelina sativa. Overexpression (OE) ofFAX1andABCA9increased seed weight and size, withFAX1-OEs andABCA9-OEs increasing seed length and width, respectively, whereasFAX1/ABCA9-OEs increasing both.FAX1-OE andABCA9-OE displayed additive effects on seed oil content and seed yield. Also, OE ofFAX1andABCA9affected membrane lipid composition in developing pods, especially on phosphatidylcholine, phosphatidylethanolamine, and phosphatidylglycerol. The expression of some genes involved in seed oil synthesis, such asDGAT2,PDAT1, andLEC1, was increased in developing seeds ofFAX1- and/orABCA9-OEs.

Conclusion

These results indicate that increased expression ofFAX1andABCA9can potentially be applied to improving camelina oil production.
Targeting hydroxycinnamoyl CoA: shikimate hydroxycinnamoyl transferase for lignin modification in Brachypodium distachyon
Authors: Serrani-Yarce Juan Carlos , Escamilla-Trevino Luis , Barros Jaime , Gallego-Giraldo Lina , Pu Yunqiao , Ragauskas Art , Dixon Richard A.
Published: February 2021

Background

Hydroxycinnamoyl CoA: shikimate hydroxycinnamoyl transferase (HCT) is a central enzyme of the so-called “esters” pathway to monolignols. As originally envisioned, HCT functions twice in this pathway, to form coumaroyl shikimate and then, in the “reverse” direction, to convert caffeoyl shikimate to caffeoyl CoA. The discovery of a caffeoyl shikimate esterase (CSE) that forms caffeic acid directly from caffeoyl shikimate calls into question the need for the reverse HCT reaction in lignin biosynthesis. Loss of function of HCT gives severe growth phenotypes in several dicot plants, but less so in some monocots, questioning whether this enzyme, and therefore the shikimate shunt, plays the same role in both monocots and dicots. The model grass Brachypodium distachyon has two HCT genes, but lacks a classical CSE gene. This study was therefore conducted to evaluate the utility of HCT as a target for lignin modification in a species with an “incomplete” shikimate shunt.

Results

The kinetic properties of recombinant B. distachyon HCTs were compared with those from Arabidopsis thaliana, Medicago truncatula, and Panicum virgatum (switchgrass) for both the forward and reverse reactions. Along with two M. truncatula HCTs, B. distachyon HCT2 had the least kinetically unfavorable reverse HCT reaction, and this enzyme is induced when HCT1 is down-regulated. Down regulation of B. distachyon HCT1, or co-down-regulation of HCT1 and HCT2, by RNA interference led to reduced lignin levels, with only modest changes in lignin composition and molecular weight.

Conclusions

Down-regulation of HCT1, or co-down-regulation of both HCT genes, in B. distachyon results in less extensive changes in lignin content/composition and cell wall structure than observed following HCT down-regulation in dicots, with little negative impact on biomass yield. Nevertheless, HCT down-regulation leads to significant improvements in biomass saccharification efficiency, making this gene a preferred target for biotechnological improvement of grasses for bioprocessing.
Elucidating the cellular mechanism for E2-induced dermal fibrosis
Authors: Baker Frost DeAnna , Savchenko Alisa , Ogunleye Adeyemi , Armstrong Milton , Feghali-Bostwick Carol
Published: February 2021

Background

Both TGFβ and estradiol (E2), a form of estrogen, are pro-fibrotic in the skin. In the connective tissue disease, systemic sclerosis (SSc), both TGFβ and E2 are likely pathogenic. Yet the regulation of TGFβ in E2-induced dermal fibrosis remains ill-defined. Elucidating those regulatory mechanisms will improve the understanding of fibrotic disease pathogenesis and set the stage for developing potential therapeutics. Using E2-stimulated primary human dermal fibroblasts in vitro and human skin tissue ex vivo, we identified the important regulatory proteins for TGFβ and investigated the extracellular matrix (ECM) components that are directly stimulated by E2-induced TGFβ signaling.

Methods

We used primary human dermal fibroblasts in vitro and human skin tissue ex vivo stimulated with E2 or vehicle (ethanol) to measure TGFβ1 and TGFβ2 levels using quantitative PCR (qPCR). To identify the necessary cell signaling proteins in E2-induced TGFβ1 and TGFβ2 transcription, human dermal fibroblasts were pre-treated with an inhibitor of the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) pathway, U0126. Finally, human skin tissue ex vivo was pre-treated with SB-431542, a TGFβ receptor inhibitor, and ICI 182,780, an estrogen receptor α (ERα) inhibitor, to establish the effects of TGFβ and ERα signaling on E2-induced collagen 22A1 (Col22A1) transcription.

Results

We found that expression of TGFβ1, TGFβ2, and Col22A1, a TGFβ-responsive gene, is induced in response to E2 stimulation. Mechanistically, Col22A1 induction was blocked by SB-431542 and ICI 182,780 despite E2 stimulation. Additionally, inhibiting E2-induced ERK/MAPK activation and early growth response 1 (EGR1) transcription prevents the E2-induced increase in TGFβ1 and TGFβ2 transcription and translation.

Conclusions

We conclude that E2-induced dermal fibrosis occurs in part through induction of TGFβ1, 2, and Col22A1, which is regulated through EGR1 and the MAPK pathway. Thus, blocking estrogen signaling and/or production may be a novel therapeutic option in pro-fibrotic diseases.
Comprehensive assessment of alterations in hand deformities over 11 years in patients with rheumatoid arthritis using cluster analysis and analysis of covariance
Authors: Toyama Shogo , Tokunaga Daisaku , Tsuchida Shinji , Kushida Rie , Oda Ryo , Kawahito Yutaka , Takahashi Kenji
Published: February 2021

Background

Although drug therapy for rheumatoid arthritis (RA) has recently improved, treating patients with established disease, whose hands have three major deformities (thumb deformity, finger deformities, and ulnar drift), remains a challenge. The underlying complex pathophysiology makes understanding these deformities difficult, and comprehensive assessment methods require accumulated skill with long learning curves. We aimed to establish a simpler composite method to understand the pathophysiology of and alterations in the hand deformities of patients with RA.

Methods

We established a rheumatoid hand cohort in 2004 and clinically evaluated 134 hands (67 patients). We repeated the evaluations in 2009 (100 hands of 52 patients) and 2015 (63 hands of 37 patients) after case exclusion. Thumb deformities, finger deformities (swan-neck and boutonnière deformity), and ulnar drift were semi-quantitated and entered as parameters into a two-step cross-sectional cluster analysis for the data in 2004. The parameters in each cluster were plotted at each evaluation point. Two-way analysis of covariance was used to examine whether differences existed between evaluation points and clusters of deformity parameters.

Results

Five clusters most appropriately described hand deformity: (i) cluster 1, minimal deformity; (ii) cluster 2, type 1 thumb deformity; (iii) cluster 3, thumb deformity and severe boutonnière deformity; (iv) cluster 4, type 2 or 3 thumb deformity and severe ulnar drift; and (v) cluster 5, thumb deformity and severe swan-neck deformity. Clusters 1 and 2 had higher function than cluster 5, and cluster 3 had moderate function. Clusters 1–4 had similar disease duration but showed different paths of deformity progression from disease onset. Clusters 1 and 2 represented conservative deformity parameters and clusters 3, 4, and 5 represented progressive deformity parameters. Over time, thumb deformity evolved into other types of deformities and swan-neck deformity worsened significantly.

Conclusions

Our comprehensive analysis identified five deformity patterns and a progressive course in the rheumatoid hand. Knowledge of the characteristics of progressive deformity parameters may allow rheumatologists to more easily implement practical interventions and determine functional prognosis.
Generating long-read sequences using Oxford Nanopore Technology from Diospyros celebica genomic DNA
Authors: Siregar Iskandar Zulkarnaen , Dwiyanti Fifi Gus , Pratama Rahadian , Matra Deden Derajat , Majiidu Muhammad
Published: February 2021

Objectives

Development of sequencing technology has opened up vast opportunities for tree genomic research in the tropics. One of the aforesaid technologies named ONT (Oxford Nanopore Technology) has attracted researchers in undertaking testings and experiments due to its affordability and accessibility. To the best of our knowledge, there has been no published reports on the use of ONT for genomic analysis of Indonesian tree species. This progress is promising for further improvement in order to acquire more genomic data for research purposes. Therefore, the present study was carried out to determine the effectiveness of ONT in generating long-read DNA sequences using DNA isolated from leaves and wood cores of Macassar ebony (Diospyros celebica Bakh.).

Data description

Long-read sequences data of leaves and wood cores of Macassar ebony were generated by using the MinION device and MinKnow v3.6.5 (ONT). The obtained data, as the first long-read sequence dataset for Macassar ebony, is of great importance to conserve the genetic diversity, understanding the molecular mechanism, and sustainable use of plant genetic resources for downstream applications.
An accelerated viscosity forward-backward splitting algorithm with the linesearch process for convex minimization problems
Authors: Suantai Suthep , Jailoka Pachara , Hanjing Adisak
Published: February 2021

In this paper, we consider and investigate a convex minimization problem of the sum of two convex functions in a Hilbert space. The forward-backward splitting algorithm is one of the popular optimization methods for approximating a minimizer of the function; however, the stepsize of this algorithm depends on the Lipschitz constant of the gradient of the function, which is not an easy work to find in general practice. By using a new modification of the linesearches of Cruz and Nghia [Optim. Methods Softw. 31:1209–1238, 2016] and Kankam et al. [Math. Methods Appl. Sci. 42:1352–1362, 2019] and an inertial technique, we introduce an accelerated viscosity-type algorithm without any Lipschitz continuity assumption on the gradient. A strong convergence result of the proposed algorithm is established under some control conditions. As applications, we apply our algorithm to solving image and signal recovery problems. Numerical experiments show that our method has a higher efficiency than the well-known methods in the literature.
A rare case report: an inextricable shoulder pain as the exclusive presentation of lung adenocarcinoma with metastasis over contralateral clavicle
Authors: Wu Karl , Huang Yu-Hao
Published: February 2021

Background

Lung cancer is the fourth most common form of the tumor spreading to the bone. Among all patients of lung carcinoma, the most common sites of bone metastasis are vertebrae, ribs, and pelvis. By comparison, the clavicle is an extremely rare site of metastases not only in the population of lung cancers but among all types of tumors. Enlightened by this existing fact, we would like to share our experience of management of an uncommon clavicular metastasis and illuminate the obscure mechanism of its scarcity.

Case presentation

A 56-year-old female without any preknown systemic disease had suffered from a sole intermittent right shoulder pain without any other discomfort for 3 months. Physical examination performed at our orthopedic department showed tenderness over the right distal third of the clavicle with limited range-of-motion of the right shoulder. EGFR-mutated lung adenocarcinoma with metastasis over the right clavicle resulting in a pathological fracture was diagnosed according to the result of the incisional biopsy. Concurrent chemoradiation therapy accompanied with target therapy was performed. Eighteen months postoperatively, the clavicle pain was found to be subsided with stationary bony lesion under appropriate medication and palliative radiotherapy during the subsequent follow-up.

Conclusions

The clavicle is an exceedingly unusual site with 2% of metastatic involvement of all type of tumors and only 1% among the population of carcinoma of lung due to its scanty red marrow and sparse vascular supply. Despite the unpleasant prognosis of clavicular metastasis from primary lung adenocarcinoma, promising quality of life is achievable under multidisciplinary management.
Impact of segmentation and discretization on radiomic features in 68Ga-DOTA-TOC PET/CT images of neuroendocrine tumor
Authors: Liberini Virginia , De Santi Bruno , Rampado Osvaldo , Gallio Elena , Dionisi Beatrice , Ceci Francesco , Polverari Giulia , Thuillier Philippe , Molinari Filippo , Deandreis Désirée
Published: February 2021

Objective

To identify the impact of segmentation methods and intensity discretization on radiomic features (RFs) extraction from 68Ga-DOTA-TOC PET images in patients with neuroendocrine tumors.

Methods

Forty-nine patients were retrospectively analyzed. Tumor contouring was performed manually by four different operators and with a semi-automatic edge-based segmentation (SAEB) algorithm. Three SUVmax fixed thresholds (20, 30, 40%) were applied. Fifty-one RFs were extracted applying two different intensity rescale factors for gray-level discretization: one absolute (AR60 = SUV from 0 to 60) and one relative (RR = min-max of the VOI SUV). Dice similarity coefficient (DSC) was calculated to quantify segmentation agreement between different segmentation methods. The impact of segmentation and discretization on RFs was assessed by intra-class correlation coefficients (ICC) and the coefficient of variance (COVL). The RFs’ correlation with volume and SUVmax was analyzed by calculating Pearson’s correlation coefficients.

Results

DSC mean value was 0.75 ± 0.11 (0.45–0.92) between SAEB and operators and 0.78 ± 0.09 (0.36–0.97), among the four manual segmentations. The study showed high robustness (ICC > 0.9): (a) in 64.7% of RFs for segmentation methods using AR60, improved by applying SUVmax threshold of 40% (86.5%); (b) in 50.9% of RFs for different SUVmax thresholds using AR60; and (c) in 37% of RFs for discretization settings using different segmentation methods. Several RFs were not correlated with volume and SUVmax.

Conclusions

RFs robustness to manual segmentation resulted higher in NET 68Ga-DOTA-TOC images compared to 18F-FDG PET/CT images. Forty percent SUVmax thresholds yield superior RFs stability among operators, however leading to a possible loss of biological information. SAEB segmentation appears to be an optimal alternative to manual segmentation, but further validations are needed. Finally, discretization settings highly impacted on RFs robustness and should always be stated.
The effect of clay content on the relation between uniaxial compressive strength and needle penetration index for clay-bearing rocks
Authors: Kahraman Sair , Aloglu A. Sercan , Saygin Egemen , Aydin Bilal
Published: February 2021

The needle penetration index (NPI) test is a non-destructive test that is applicable both in the field and laboratory, and does not require any special sample preparation. This test has been used for the estimation of physico-mechanical properties of soft rocks. In this study, the influence of the clay content on the relation between uniaxial compressive strength (UCS) and the NPI has been investigated for some clay-bearing rocks. The needle penetration tests were carried out at nine different gallery faces during the Cayirhan Coal Mine excavations, and the NPI values were calculated. Claystone, clayey limestone and clay blocks were collected from the locations on which the NPI tests were performed for the determination of rock strength and clay contents. The clay contents and clay fractions of the samples were determined using XRD analysis. A strong correlation has been found between the UCS and the NPI, but some of the data points were scattered. Strong correlations were also found between the NPI and both the total clay content and the smectite content. The UCS values were also strongly correlated to the total clay content and the smectite content. A multiple regression analysis was performed to determine the influence of clay content on the UCS-NPI relation and a very strong model was derived. The correlation coefficient of the multiple regression model is fairly higher than that of the UCS-NPI relation derived by using simple regression analysis. Concluding remark is that the clay content significantly affects the UCS-NPI relation in clay-bearing rocks.
Use of a Rigid Bronchoscope as the Sole Prebypass Airway During Pediatric Tracheal Tumor Resection: A Case Report
Authors: Evans Michael A. , Stephens Elizabeth H. , Lavin Jennifer M. , Chun Yeona , Maurrasse Sarah , Backer Carl L.
Published: February 2021

We describe the anesthetic and operative techniques utilized for a tracheal tumor resection in a pediatric patient with 95% tracheal occlusion. In prior tracheal tumor cases that dictated complete resection, our team had been able to comfortably bypass a tumor with an endotracheal tube. In this case, we could not intubate past the tumor. A rigid bronchoscope was able to be placed past the tumor, so we continued with sternotomy and dissection before cardiopulmonary bypass while ventilating through that bronchoscope as our definitive airway.
Fast-Track Cardiac Anesthesia Aids in the Early Diagnosis of Lower Extremity Compartment Syndrome: A Case Report
Authors: Syski Andrew L. , Crane Jeremy M. , Hodgson John A.
Published: February 2021

A 21-year-old otherwise healthy male with severe asymptomatic mitral regurgitation underwent a mitral valve repair via right thoracotomy and right femoral cannulation for cardiopulmonary bypass. Due to his age and health status, the anesthetic was planned to facilitate early extubation. Immediately on arrival to the intensive care unit, the patient complained of severe right calf pain with decreased sensation of the plantar foot. He was diagnosed with compartment syndrome and was taken back to the operating room for emergent 4-compartment fasciotomy. The fast-track anesthetic allowed for early diagnosis and treatment and prevented a likely catastrophic outcome.
Evolution of the ACSM Guidelines
Authors: Franklin Barry A.
Published: February 2021

Apply it!

This article summarizes recent advances in exercise testing and prescription for varied populations, environments, and medical conditions, including brain-related diseases, as detailed in the just released 11th edition of ACSM’s Guidelines for Exercise Testing and Prescription.

▪ This article provides a historical perspective, new insights, and practical implications of the recently released 11th edition of ACSM’s Guidelines for Exercise Testing and Prescription.

▪ This article summarizes key recent findings relative to exercise testing, exercise training, and exercise prescription in the prevention and treatment of cardiovascular disease.
Post operative sore throat: Comparison between Macintosh versus Video Laryngoscope in patients intubated by trainee anaesthetists - A Randomised Control Trial
Authors: Kapadia Amin Ahmed , Shafiq Faraz , Raza Amir
Published: February 2021

Objectives: Postoperative sore throat (POST) is a common complication related to endotracheal intubation. The aim of this study was to compare the incidence of POST in patients intubated by trainee anaesthetist using Video LaryngoscopeTM (VDL) or Conventional Macintosh Laryngoscope (CL).

Methods: Total 110 patient scheduled for elective laparoscopic cholecystectomy were included from main operating room of Aga Khan University Hospital between June 2017-2018. The standardized perioperative protocol was used for general anaesthesia. Selected patients were randomly allocated into conventional laryngoscopy (CL) group or video laryngoscopy (VDL) group. The evaluation of sore throat was done at 1st, 12th and 24th hour postoperatively using a ten-point visual analogue scale.

Results: The demographic characteristics, including intubation time, related complications or any other maneuver required were similar between the groups. The incidence of POST at 1st hour was 47% patients in CL group and 38% in VDL group (p=0.335). At 12th hour, 34.5% patients in CL and 38% in VDL reported POST (p=0.692). Similarly at 24th hour, 25% patients in CL and 16% in VDL group reported POST (p=0.669).

Conclusions: There was no significant difference in incidence of POST for patients intubated by trainee anaesthetists using either CL or VDL. Objective evidence of training and laryngoscope technique can impact of POST.

Registered at ClinicalTrials.gov Identifier: NCT04334616.

doi: https://doi.org/10.12669/pjms.37.3.3365

How to cite this:Kapadia AA, Shafiq F, Raza A. Post operative sore throat: Comparison between Macintosh versus Video Laryngoscope in patients intubated by trainee anaesthetists - A Randomised Control Trial. Pak J Med Sci. 2021;37(3):764-769.  doi: https://doi.org/10.12669/pjms.37.3.3365

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Resilience and its relationship with spiritual wellbeing among patients with heart failure
Authors: Razaghpoor Ali , Rafiei Hossein , Taqavi Fateme , Hashemi Seyedeh Mahnaz
Published: February 2021

Background/Aims

The importance of resilience among patients with chronic diseases has been demonstrated, but rarely among patients with heart failure. This study examines resilience and its relationship with spiritual wellbeing among this patient group.

Methods

This descriptive study was carried out with 130 patients with heart failure in Iran. The tools used were a 29-item resilience scale and the Paloutzian and Ellison Spiritual Wellbeing scale.

Results

The average resilience score was 107±19.5. Among the demographic variables, age, education, duration of disease and the presence of other concomitant diseases were significantly correlated with the patients' total resilience scores (P<0.05). The average spiritual wellbeing score was 83.12, with results showing a significant and direct relationship between resilience and spiritual wellbeing (P=0.001, r=0.386).

Conclusions:

Levels of resilience have a strong relationship with spiritual wellbeing among patients with heart failure. Therefore, building resilience should be incorporated into holistic care of these patients.
Challenges and opportunities identified for lymphoedema services in Wales during the COVID-19 pandemic
Authors: Gabe-Walters Marie , Noble-Jones Rhian
Published: February 2021

Background:

During the COVID-19 pandemic, lymphoedema staff adapted services, providing care remotely, and worked in other NHS sectors. The impact on services and staff must be understood in order to safeguard patient care and foster workforce resilience.

Aims:

To evaluate the experiences of clinical and non-clinical lymphoedema staff in Wales during the COVID-19 pandemic.

Methods:

An anonymous online survey, based on scoping work, was sent out via the Welsh lymphoedema services mailing list.

Findings:

71% (68/96) of eligible lymphoedema staff completed the survey. More than half supported lymphoedema services (40/68) with the remaining staff deployed elsewhere. Overall, staff and services felt prepared for new ways of working. Concerns about others and the future burden on services when life returned to normal were reported. Opportunities identified included education initiatives and virtual services.

Conclusion:

Lymphoedema services were well prepared to deliver virtually, enable effective care and share knowledge. Co-ordinated efforts to uphold patient advocacy will support virtual services to meet their needs.
Guidelines for managing people with lymphoedema remotely: a post-COVID-19 response document
Authors: Noble-Jones Rhian , Thomas Melanie J , Lawrence Paula , Pike Cheryl
Published: February 2021

During the COVID-19 pandemic it was initially not possible to see people with lymphoedema face-to-face at lymphoedema services, due to the potential risks of the virus, because they were shielding, because of redeployment of rooms or staff, and due to sporadic restrictions of movement. The pandemic therefore accelerated adjustments in lymphoedema service delivery, while ensuring effective and efficient care was paramount. This document presents a pragmatic guide for lymphoedema services. Although clinical and non-clinical staff need to comply with guidance from their own organisations/commissioners, this document aims to provide specific guidance and share good practice in relation to lymphoedema management. These guidelines are based on analysis of the national response of Lymphoedema Network Wales during the first few months of the COVID-19 pandemic and incorporate supporting contemporary advice. They have been used throughout NHS Wales, providing a standardised approach in supporting care for people with lymphoedema. In light of the enduring nature of COVID-19, it is imperative that lymphoedema services have a means to provide suitable care for patients. Although face-to-face appointments are sometimes deemed necessary, many patients can be suitably supported via telehealth consultations. These guidelines may help lymphoedema services restore and reset in a safe and acceptable manner.
Establishing a nurse-led thyroid cancer follow-up clinic
Authors: Fishburn Andrew , Fishburn Nicola
Published: February 2021

Thyroid cancer is a complex disease requiring management by a large multidisciplinary team. The number of patients with a diagnosis of thyroid cancer is significantly increasing year-on-year, and traditional models of consultant-led follow up are no longer sustainable. Although nurse-led cancer follow-up clinics are becomining increasingly common, thyroid cancer nurse-led follow-up clinics are rare. An excellent understanding of the disease, treatment and management of risk of disease recurrence is essential for safe patient care, and is discussed in this article. The clinic discussed uses the skill set of head and neck nurse specialists, including psychological support, coping strategies for long-term side effects of treatment and non-medical prescribing. A patient survey of the service revealed high levels of patient satisfaction and a desire to continue face-to-face consultations rather than telephone clinics.