bluuebunny/crossref_metadata_2025 huggingface dataset:
Total Anomalous Pulmonary Venous Connection and Aortopulmonary Window: Successful Management of a Rare Association
Authors: Katewa Ashish , Sahu Balswaroop , Gajpal Shivani , Anderson Robert H.
Published: May 2021

The association of total anomalous pulmonary venous connection (TAPVC) with aortopulmonary window (APW) is extremely rare. The coexistence of these two anomalies will have implications on clinical presentation, diagnosis, and pathophysiology. The lungs are exposed to pulmonary venous hypertension due to obstructed TAPVC as well as pulmonary arterial hypertension due to unrestrictive APW. We describe successful management of this unusual association in a three-month-old child.
The Influence of Emotion and Empathy on Decisions to Help Others
Authors: Xiao Weilong , Lin Xue , Li Xinwei , Xu Xiaofei , Guo Huanen , Sun Binghai , Jiang Huaibin
Published: May 2021

Many decisions to help others are made in emotionally associated circumstances. Empathy is known to motivate prosocial behavior. However, no studies have investigated the interaction between empathy and emotion in deciding to help others. In total, 151 students scoring either high or low in empathy viewed three types of emotional clips (anger vs. sadness vs. neutrality) and completed the “Help for Another Study” task. Analysis of variance showed that participants chose to invest more time in helping others when they felt sadness than anger. Participants with high empathy chose to spend more time helping others than those with low empathy. Pearson’s correlation revealed a significant positive correlation between perspective-taking, empathic concern, and willingness to invest time in assistance under anger state; perspective-taking and fantasy were significantly correlated with willingness to invest time under sadness state. The results suggest that both emotion (i.e., sadness) and empathy (i.e., high trait empathy) are vital motivators that exert impact on prosocial helping decisions.
Correlation of Ultrasound Findings With Clinical Stages and Impairment in Adhesive Capsulitis of the Shoulder
Authors: Do Jong Geol , Hwang Jin Tae , Yoon Kyung Jae , Lee Yong-Taek
Published: May 2021

Background:

Ultrasound is an essential tool for diagnosing shoulder disorders. However, the role of ultrasound in assessing and diagnosing adhesive capsulitis has not been fully studied.

Purpose:

To evaluate the ultrasound features of adhesive capsulitis and estimate the correlations between clinical impairment and ultrasound parameters.

Study Design:

Case series; Level of evidence, 4.

Methods:

A total of 61 patients with clinically diagnosed unilateral adhesive capsulitis were retrospectively reviewed using high-resolution ultrasound. To compare ultrasound parameters, we performed ultrasound examinations on both affected and unaffected shoulders. Ultrasound parameters, including thickness of the coracohumeral ligament (CHL), rotator interval (RI), axillary recess (AR), hypervascularity of the RI, and effusion of the long head of the biceps tendon sheath, were measured. Passive range of motion (PROM), visual analog scale for pain, and the Shoulder Pain and Disability Index were used for clinical assessment.

Results:

The CHL, the RI, and the AR in affected shoulders were significantly thicker than in unaffected shoulders ( P < .05). CHL thickness in affected shoulders was significantly correlated with PROM limitation, which included forward elevation, abduction, external rotation (ER), and internal rotation (IR) ( P < .05). AR thickness correlated with passive forward elevation limitation and passive IR limitation ( P < .05). The CHL was significantly thicker in stage 2 compared with stage 1, and the RI was thicker in stage 2 compared with stage 3. The diagnostic cutoff values for adhesive capsulitis were 2.2 mm for CHL thickness (77% sensitivity, 91.8% specificity) and 4 mm for AR thickness (68.9% sensitivity, 90.2% specificity).

Conclusion:

The ultrasound parameters associated with structural changes were correlated with clinical characteristics of adhesive capsulitis. Thickened CHL, RI, and AR were observed in affected shoulders. The cutoff values of 2.2 mm for CHL thickness and 4 mm for AR thickness can be used as cutoff diagnostic values for adhesive capsulitis.
Pain and Management of Pain: A Clinical Review for Craniofacial Surgeons
Authors: Yu Jack C. , Yu Jaclyn M. , Shukla Dhairya , Lima Maria H. , Doroodchi Atbin , Munoz Monaco Gustavo , Baban Babak
Published: May 2021

Frequently, aches, and pain are symptoms, like alarms alerting the occurrences of dangerous events which can cause cell death, tissue destruction, and inflammation. Physicians treat the underlying diseases which cause the pain and aches in order to restore health. On some occasions, the treatments are directed at aches and pains themselves, and are thus symptomatic relief. For surgeons, pain is an inevitable consequence of what we do in the operating room. Postoperative pain management represents an important part of the Enhanced Recovery After Surgery (ERAS) protocols. Furthermore, opioid epidemic has cost a great burden on the society and the healthcare system, which also places an emphasis on using non-opioid analgesics to achieve adequate pain relief. Unlike other vital signs, there is no objective, direct measurement of pain, even though pain is considered the fourth vital sign. Pain is a perceived sensation, as a result of nociception, a complex process which can extend from other somatosensory modalities such as thermoception, chemoception, and mechanoception. Whenever the stimulus magnitude exceeds nominal physiologic boundaries, cell death, and tissue injury follow, as does afferent nociceptive signals. This review is to provide craniofacial surgeons with an update on pain, what pain is, how to assess it, pharmacology of pain relief, and specifically, the proper use of opioids and non-narcotic analgesic agents. The goal is to allow for the optimal, rational use of these medications to relief pain with the minimum short and long term risks. With evidence-based, data-driven approach, supplemented by group experience pooled from senior surgeons after 100,000 patient-hours, the objective is to answer the following: (1) What is pain? (2) How does opioid work? (3) What is the role of narcotic analgesics in craniofacial ERAS? (4) When should non-opioids be used and how?
VEXAS Syndrome
Authors: Grayson Peter C , Patel Bhavisha A , Young Neal S
Published: May 2021

VEXAS syndrome is a monogenic disease of adulthood caused by somatic mutations in UBA1 in hematopoietic progenitor cells. Patients present with a range of inflammatory and hematologic symptoms (Visual Abstract). Myeloid-driven autoinflammation and progressive bone marrow failure lead to substantial morbidity and mortality. Effective medical treatments, beyond glucocorticoids, need to be identified. Reports in the current issue of Blood describe novel UBA1 genetic variants, treatment options, and insight into disease pathophysiology. VEXAS syndrome represents a prototype for a new class of diseases.
Censcyt: censored covariates in differential abundance analysis in cytometry
Authors: Gerber Reto , Robinson Mark D.
Published: May 2021

Background

Innovations in single cell technologies have lead to a flurry of datasets and computational tools to process and interpret them, including analyses of cell composition changes and transition in cell states. Thediffcytworkflow for differential discovery in cytometry data consist of several steps, including preprocessing, cell population identification and differential testing for an association with a binary or continuous covariate. However, the commonly measured quantity of survival time in clinical studies often results in a censored covariate where classical differential testing is inapplicable.

Results

To overcome this limitation, multiple methods to directly include censored covariates in differential abundance analysis were examined with the use of simulation studies and a case study. Results show that multiple imputation based methods offer on-par performance with the Cox proportional hazards model in terms of sensitivity and error control, while offering flexibility to account for covariates. The tested methods are implemented in the packagecenscytas an extension ofdiffcytand are available athttps://bioconductor.org/packages/censcyt.

Conclusion

Methods for the direct inclusion of a censored variable as a predictor in GLMMs are a valid alternative to classical survival analysis methods, such as the Cox proportional hazard model, while allowing for more flexibility in the differential analysis.
Severe secondary hyperkalemia and arrhythmia from drug interactions between calcium‐channel blocker and voriconazole: a case presentation
Authors: Zhao Xinju , Zhang Chunyan , Zhu Li , Wu Bei , Han Yun , Heung Michael , Zuo Li
Published: May 2021

Background

Patients with kidney disease may have concurrent hypertension and infection. Dihydropyridine calcium-channel blockers (CCB) are the most popular class of antihypertensive drugs used in clinical settings and can be metabolized by cytochrome P450 isoenzyme 3A4 (CYP3A4). Voriconazole is a commonly used antifungal treatment and a CYP3A4-inhibitor. Insufficient attention to drug interactions from the concomitant use of CCB and voriconazole may result in serious adverse reactions.

Case presentation

Here, we report a patient with acute kidney injury on stable anti-neutrophil cytoplasm antibody associated vasculitis who developed hyperkalemia resulting in sinus arrest with junctional escape rhythm attributed to drug interactions of CCB with voriconazole. This is a very rarely reported case and may be an under-recognized complication. After continuous renal replacement therapy and changing the anti-hypertensive drugs, symptoms, and laboratory abnormalities of the patient fully recovered.

Conclusions

This case warns us of severe consequences of drug interactions. Co-prescription of CYP3A4-inhibitors with calcium-channel blockers increases the risk of hypotension and acute kidney injury, which may further induce hyperkalemia and arrhythmia.
Impact of relative dose intensity of oxaliplatin in adjuvant therapy among stage III colon cancer patients on early recurrence: a retrospective cohort study
Authors: Żok Jolanta , Bieńkowski Michał , Radecka Barbara , Korniluk Jan , Adamowicz Krzysztof , Duchnowska Renata
Published: May 2021

Background

Oxaliplatin-based therapy with FOLFOX-4 or CAPOX administered over 6 months remains the standard adjuvant treatment for stage III colon cancer (CC) patients. However, many patients experience dose reduction or early termination of chemotherapy due to oxaliplatin toxicity, which may increase the risk of early recurrence. The objective of this study was to analyze the relationship between the relative dose intensity of oxaliplatin (RDI-O) and early recurrence among stage III CC patients.

Methods

The study included 365 patients treated at five oncology centers in Poland between 2000 and 2014. Survival analysis was performed using the Kaplan-Meier method. Univariate analysis was performed using the Cox proportional hazard model; multivariate analysis was performed with the stepwise forward approach. For all analyses the α level of 0.05 was employed.

Results

The median follow-up was 51.8 months (range 8.2–115.1). Early recurrence < 36 months after surgery occurred in 130 patients (37.8%). In this group 51 (39.2%) and 87 (66.9%) of patients were low and high-risk, respectively. Receipt < 60% of RDI-O was associated with early recurrence within 18 months after surgery (OR = 2.05; 95%CI: 1.18–3.51; p = 0.010), especially in low-risk group (HR = 1.56 (95%CI: 0.96–2.53), p = 0.07). In the multivariate analysis early recurrence was correlated with grade (OR = 2.47; 95% CI: 1.25–4.8; p = 0.008), pN (OR = 2.63; 95% CI: 1.55–4.54; p < 0.001), the number of lymph nodes harvested (OR = 0.51; 95% CI: 0.29–0.86; p = 0.013) and RDI-O (OR = 1.91; 95%CI: 1.06–3.39; p = 0.028). The early vs. late recurrence negatively correlated with OS regardless of the RDI-O (HR = 22.9 (95%CI: 13.9–37.6; p < 0.001).

Conclusions

RDI-O < 60% in adjuvant therapy among stage III CC (especially in low-risk group) increases the risk of early recurrence within 18 months of surgery. Patients with early recurrence showed worse overall survival regardless of the RDI-O.
Exploring the local policy context for reducing health inequalities in children and young people: an in depth qualitative case study of one local authority in the North of England, UK
Authors: Holding Eleanor , Fairbrother Hannah , Griffin Naomi , Wistow Jonathan , Powell Katie , Summerbell Carolyn
Published: May 2021

Background

Improving children and young people’s (CYP) health and addressing health inequalities are international priorities. Reducing inequalities is particularly pertinent in light of the Covid-19 outbreak which has exacerbated already widening inequalities in health. This study aimed to explore understandings of inequality, the anticipated pathways for reducing inequalities among CYP and key factors affecting the development and implementation of policy to reduce inequalities among CYP at a local level.

Methods

We carried out a qualitative case study of one local government region in the North of England (UK), comprising semi structured interviews (n = 16) with service providers with a responsibility for child health, non-participant observations of key meetings (n = 6 with 43 participants) where decisions around child health are made, and a local policy documentation review (n = 11). We employed a novel theoretical framework, drawing together different approaches to understanding policy, to guide our design and analysis.

Results

Participants in our study understood inequalities in CYP health almost exclusively as socioeconomically patterned inequalities in health practices and outcomes. Strategies which participants perceived to reduce inequalities included: preventive support and early intervention, an early years/whole family focus, targeted working in local areas of high deprivation, organisational integration and whole system/place-based approaches. Despite demonstrating a commitment to a social determinants of health approach, efforts to reduce inequalities were described as thwarted by the prevalence of poverty and budget cuts which hindered the ability of local organisations to work together. Participants critiqued national policy which aimed to reduce inequalities in CYP health for failing to recognise local economic disparities and the interrelated nature of the determinants of health.

Conclusions

Despite increased calls for a ‘whole systems’ approach to reducing inequalities in health, significant barriers to implementation remain. National governments need to work towards more joined up policy making, which takes into consideration regional disparities, allows for flexibility in interpretation and addresses the different and interrelated social determinants of health. Our findings have particular significance in light of Covid-19 and indicate the need for systems level policy responses and a health in all policies approach.
Temporal summation of mechanical pain prospectively predicts movement-evoked pain severity in adults with chronic low back pain
Authors: Overstreet Demario S. , Michl Ava N. , Penn Terence M. , Rumble Deanna D. , Aroke Edwin N. , Sims Andrew M. , King Annabel L. , Hasan Fariha N. , Quinn Tammie L. , Long D. Leann , Sorge Robert E. , Goodin Burel R.
Published: May 2021

Background

Biopsychosocial factors above and beyond pathoanatomical changes likely contribute to the severity of chronic low back pain. A pro-nociceptive endogenous pain modulatory balance (↓inhibition and ↑facilitation) may be an important contributor to chronic low back pain severity and physical function; however, additional research is needed to address this possibility. The objective of this study was to determine whether quantitative sensory tests of endogenous pain inhibition and facilitation prospectively predict movement-evoked pain and cLBP severity self-reported on a validated questionnaire.

Methods

One hundred thirty-four individuals with chronic low back pain were enrolled in this two-session study. During the first study session, temporal summation of mechanical pain and conditioned pain modulation were assessed at the lumbar spine to determine endogenous pain facilitation and inhibition, respectively. One week later, participants returned for a second study session whereby they reported their pain severity and pain interference using the Brief Pain Inventory-Short Form. Movement-evoked pain and physical function capacity were assessed upon completion of the balance, walking, and transition from sit to stand tests of the Short Physical Performance Battery.

Results

Temporal summation of mechanical pain, but not conditioned pain modulation, significantly and prospectively predicted greater movement-evoked pain and poorer physical function on the Short Physical Performance Battery. Neither temporal summation nor conditioned pain modulation were significantly related to self-reported pain severity or pain interference on the Brief Pain Inventory-Short Form.

Conclusions

Findings suggest that a pro-nociceptive pain modulatory balance characterized by enhanced pain facilitation may be an important driver of movement-evoked pain severity and poor physical function in individuals with chronic low back pain.
Why clinical training in China should improve: a cross-sectional study of MD graduates
Authors: Zhang Xiaoning , Li Chong , Yue Cailing , Jiang Xue , Cao Junli , ten Cate Olle
Published: May 2021

Background

China is experiencing major medical education reforms that include establishing national training standards, standards for health professionals, and advanced health delivery system requirements. Graduate medical education (GME) is being piloted as a merger of Doctor of Medicine (MD) with PhD programs to improve academic research and clinical training. However, the academic degree-centred system has led to a preoccupation with research rather than clinical training. Unfortunately, there is a shortage of quality information regarding the clinical training of MD graduates from Chinese medical schools. To fill this gap, this general investigation aims to provide the perspective of recent MD graduates in China for the different subspecialties of clinical training as experienced in different contexts.

Methods

There were 432 MD graduates who participated in an online survey regarding their clinical training. Information collected included overall satisfaction, educational supervision, supervised learning events, curriculum coverage, local teaching, teamwork, educational governance, workload, supportiveness of the environment, feedback, clinical experience, patient safety, handovers, and reporting systems.

Results

Only 37.4% reported satisfaction with the overall clinical training quality; 54.6% rated the informal and bedside quality as “good”; 64.4% reported they knew who provided clinical supervision; but only 35.5% rated the quality of clinical supervision as high; 51.8% reported that they judged senior physicians as “not competent”; 41.9% agreed that the staff treated each other respectfully; 97.4% admitted that they worked beyond the mandatory hours and claimed they were regularly short of sleep; 84.2% raised concerns about patient safety; 45.3% reported that they received regular informal feedback; 48.1% believed that their concerns about education and training would be addressed.

Conclusions

This study suggests that the quality of clinical training for MD graduates should be improved. While the overall satisfaction with the teaching quality was acceptable, the quality of many clinical training aspects scored poorly. A major problem seems an undue focus on research in MD/PhD training at the cost of the quality of clinical training, due to career perspectives that undervalue clinical competence. The findings of this study should benefit from a deeper investigation to understand the causes and possible remediation. Suggestions include defining subspecialties and training lengths; monitoring, evaluation, and integration SST with MD degree; providing funds or rewards for academic and clinical training; establishing supervising teams to guide clinical training; and establishing physician scientist task force to help overcome challenges.
The experiences, attitudes and understanding of research amongst medical students at an Australian medical school
Authors: Muhandiramge Jaidyn , Vu Tony , Wallace Megan J. , Segelov Eva
Published: May 2021

Background

Research engagement plays an integral role in developing clinicians that practice effective, evidence-based medicine. Research participation by clinicians, however, is declining. Given the link between research during medical school and future research output, promotion of medical student research is one avenue by which this shortage can be addressed. Student research attitudes and participation in Australia are not well-documented in the literature. This study therefore aims to investigate research practices, motivators, and barriers amongst Australian medical students in order to determine whether there is a need for further integration of research within Australian medical school curriculums.

Methods

A cross-sectional study design was used to explore research experience and attitudes, as well as the enablers and barriers to research amongst students enrolled in all years of the five-year medical course at Monash University. A questionnaire was created by combining questions from several surveys on medical student research and comprised Likert scales, multiple choice options and free-text responses assessing research experience, attitudes, motivators, and barriers.

Results

Seven hundred and four respondents (69.4% female; survey response rate 36.7%) reported variable research experience and interest. Less than half of the cohort (n = 296; 44.9%) had contributed to a research project. Increasing employability for specialty training programs was the primary motivating factor (n = 345; 51.9%) for pursuing research, with only 20.5% (n = 136) citing an interest in academia as a motivator. Time constraints (n = 460; 65.3%) and uncertainty surrounding how to find research opportunities (n = 449; 63.8%) were the most common barriers to research.

Conclusions

Medical students at Monash University are interested in but have limited experience with research. Students are, however, primarily motivated by the prospect of increasing employability for specialist training; medical schools should therefore focus on encouraging intrinsic motivation for pursuing research. Greater integration of research education and opportunities within medical school curricula may also be required to provide students with the skills necessary to both pursue research and practice evidence-based medicine.
Stigma about mental disease in Portuguese medical students: a cross-sectional study
Authors: Moreira Ana-Raquel , Oura Maria-Joao , Santos Paulo
Published: May 2021

Background

The stigma about mental diseases is common in the population and also in medical students, where it may condition their future practice and the way they deal with these patients.

Aim

To evaluate and characterize the stigma on mental diseases in Portuguese sixth-year medical students, based on a clinical scenario of a classmate suffering from a mental disorder.

Methods

Observational cross-sectional study, involving sixth-year students of all Portuguese medical schools. We applied an online self-response questionnaire, using the Portuguese version of the Attribution Questionnaire AQ-9, and a vignette of a classmate colleague, presenting mental illness symptoms. Stigma scores were calculated. We used logistic regression to estimate the effect of social determinants on stigma pattern, and we analysed the correlation between 9 variables evaluated by the AQ-9 and total stigma.

Results

A total of 501 participants were included for analysis (69.5% females, median age of 24 years old). Medical students were available to help in the proposed clinical scenario (6.93/9.00; 95%CI:6.77–7.10), if necessary using coercion for treatment (3.85; 95%CI:3.63–4.07), because they felt pity (6.86; 95%CI:6.67–7.06) and they perceived some kind of dangerousness (4.06; 95%CI:3.84–4.28). Stigma was lower in students having a personal history of mental illness (OR:0.498; 95%CI:0.324–0.767; p = 0.002) and in those with positive familial history (OR: 0.691; 95%CI:0.485–0.986; p = 0.041).

Conclusion

Our results show the importance of implementing anti-stigma education, to improve medical students’ attitudes towards peers living with mental diseases.
Precision medicine and the principle of equal treatment: a conjoint analysis
Authors: Tranvåg Eirik Joakim , Strand Roger , Ottersen Trygve , Norheim Ole Frithjof
Published: May 2021

Background

In precision medicine biomarkers stratify patients into groups that are offered different treatments, but this may conflict with the principle of equal treatment. While some patient characteristics are seen as relevant for unequal treatment and others not, it is known that they all may influence treatment decisions. How biomarkers influence these decisions is not known, nor is their ethical relevance well discussed.

Methods

We distributed an email survey designed to elicit treatment preferences from Norwegian doctors working with cancer patients. In a forced-choice conjoint analysis pairs of hypothetical patients were presented, and we calculated the average marginal component effect of seven individual patient characteristics, to estimate how each of them influence doctors’ priority-setting decisions.

Results

A positive biomarker status increased the probability of being allocated the new drug, while older age, severe comorbidity and reduced physical function reduced the probability. Importantly, sex, education level and smoking status had no significant influence on the decision.

Conclusion

Biomarker status is perceived as relevant for priority setting decisions, alongside more well-known patient characteristics like age, physical function and comorbidity. Based on our results, we discuss a framework that can help clarify whether biomarker status should be seen as an ethically acceptable factor for providing unequal treatment to patients with the same disease.
Implementing a telehealth prehabilitation education session for patients preparing for major cancer surgery
Authors: Waterland Jamie L. , Chahal Rani , Ismail Hilmy , Sinton Catherine , Riedel Bernhard , Francis Jill J. , Denehy Linda
Published: May 2021

Background

Prehabilitation services assist patients in preparing for surgery, yet access to these services are often limited by geographical factors. Enabling rural and regional patients to access specialist surgical prehabilitation support with the use of telehealth technology has the potential to overcome health inequities and improve post-operative outcomes.

Aim

To evaluate the current and likely future impact of a telehealth preoperative education package for patients preparing for major abdominal cancer surgery.

Methods

A telehealth alternative to a hospital based pre-operative education session was developed and implemented at a dedicated cancer hospital. Adult patients (≥18 years) scheduled for elective major cancer surgery were offered this telehealth alternative. Impact evaluation was conducted using the RE-AIM framework.

Results

To date, 35 participants have consented to participate in the study. Thirty-one participants attended the intervention; 24 (69%) residing in rural or regional areas. Twenty-four (77%) reported that if given a choice they would prefer the online session as opposed to attending the hospital in person. The majority (97%) reported they would recommend the intervention to others preparing for surgery. Session information was recalled by all 26 participants and 77% of participants reported acting on recommendations 2 weeks after the session. Lessons learnt and recommendations for providers implementing similar programs are reported.

Conclusion

Telehealth alternatives to hospital based pre-operative education are well received by patients preparing for major cancer surgery. We make seven recommendations to improve implementation. Further evaluation of implementation strategies alongside clinical effectiveness in future studies is essential.

Trial registration

ACTRN12620000096954, 04/02/2020.
Recent advances in near-infrared II imaging technology for biological detection
Authors: Zhang Nan-nan , Lu Chen-ying , Chen Min-jiang , Xu Xiao-ling , Shu Gao-feng , Du Yong-zhong , Ji Jian-song
Published: May 2021

Molecular imaging technology enables us to observe the physiological or pathological processes in living tissue at the molecular level to accurately diagnose diseases at an early stage. Optical imaging can be employed to achieve the dynamic monitoring of tissue and pathological processes and has promising applications in biomedicine. The traditional first near-infrared (NIR-I) window (NIR-I, range from 700 to 900 nm) imaging technique has been available for more than two decades and has been extensively utilized in clinical diagnosis, treatment and scientific research. Compared with NIR-I, the second NIR window optical imaging (NIR-II, range from 1000 to 1700 nm) technology has low autofluorescence, a high signal-to-noise ratio, a high tissue penetration depth and a large Stokes shift. Recently, this technology has attracted significant attention and has also become a heavily researched topic in biomedicine. In this study, the optical characteristics of different fluorescence nanoprobes and the latest reports regarding the application of NIR-II nanoprobes in different biological tissues will be described. Furthermore, the existing problems and future application perspectives of NIR-II optical imaging probes will also be discussed.
Radiologic findings that aid in the reduction of misdiagnoses of Langerhans cell histiocytosis of the bone: a retrospective study
Authors: Zhao Mimi , Tang Limin , Sun Shiqing , Cui Jiufa , Chen Haisong
Published: May 2021

Background

This study aimed to identify the characteristic radiological signs for the diagnosis of Langerhans cell histiocytosis (LCH) of the bone.

Methods

We retrospectively studied 82 cases of LCH with bone lesions confirmed by pathology. Clinical and radiological features of the patients were analyzed.

Results

A total of 64 and 18 patients had single and multiple bone lesions, respectively. With regard to LCH with single bone lesions, 37.5% (24/64) of lesions were located in the skull and presented as bone destruction with or without soft tissue mass. The correct diagnosis rate of these lesions was 60.0% (9/15) in children and adolescents, but was only 22.2% (2/9) in adults.

A total of 26.5% (17/64) of the solitary lesions were found in the spine. Of these, 88.2% (15/17) were located in the vertebral body and appeared to have different degrees of collapse, and 66.7% (10/15) of these lesions were correctly diagnosed.

Of the unifocal lesions, 21.8% (14/64) were located in other flat and irregular bones and manifested as osteolysis. Only 21.4% (3/14) of these cases were correctly diagnosed.

In total, 14.1% (9/64) of the isolated bone LCH lesions were located in the long bones. Of these, 77.8% (7/9) were located in the diaphysis and presented as central bone destruction with or without fusiform periosteal reaction and extensive peripheral edema, of which 42.9% (3/7) were correctly diagnosed before surgery or biopsy.

With regard to LCH with multiple bony destructive lesions, 71.4% (10/14) of cases in children and adolescents were correctly diagnosed; however, all four cases among adults were misdiagnosed.

Conclusion

In all age groups, isolated diaphyseal destruction of the long bone with fusiform periosteal reaction and extensive peripheral edema, vertebra plana of the spine, and bevelled edge of skull defects accompanied by soft tissue masses strongly suggest LCH diagnosis. Moreover, the multiple bone osteolytic destruction in children and adolescents strongly suggests LCH diagnosis. Familiarity with these typical radiological signs of LCH is necessary to decrease misdiagnoses.
Covid-19 in the Caribbean: lessons learned from the ongoing international medical and scientific cooperation
Authors: Resiere Dabor , Mehdaoui Hossein , Dyer Hedda , Chabartier Cyrille , Cabié André , Inamo Jocelyn , Compton Keats , Neviere Rémi , Megarbane Bruno , Kallel Hatem
Published: May 2021

The coronavirus disease (Covid-19) crisis presents as human, social and economic challenges. The advent of Covid-19, unfortunate as it is, has highlighted the need for close medical cooperation between states. Medical cooperation is the key counter to fight against the Covid-19 pandemic.
Natural family-free genomic distance
Authors: Rubert Diego P. , Martinez Fábio V. , Braga Marília D. V.
Published: May 2021

Background

A classical problem in comparative genomics is to compute the rearrangement distance, that is the minimum number of large-scale rearrangements required to transform a given genome into another given genome. The traditional approaches in this area are family-based, i.e., require the classification of DNA fragments of both genomes into families. Furthermore, the most elementary family-based models, which are able to compute distances in polynomial time, restrict the families to occur at most once in each genome. In contrast, the distance computation in models that allow multifamilies (i.e., families with multiple occurrences) is NP-hard. Very recently, Bohnenkämper et al. (J Comput Biol 28:410–431, 2021) proposed an ILP formulation for computing the genomic distance of genomes with multifamilies, allowing structural rearrangements, represented by the generic double cut and join (DCJ) operation, and content-modifying insertions and deletions of DNA segments. This ILP is very efficient, but must maximize a matching of the genes in each multifamily, in order to prevent the free lunch artifact that would otherwise let empty or almost empty matchings give smaller distances.

Results

In this paper, we adopt the alternative family-free setting that, instead of family classification, simply uses the pairwise similarities between DNA fragments of both genomes to compute their rearrangement distance. We adapted the ILP mentioned above and developed a model in which pairwise similarities are used to assign weights to both matched and unmatched genes, so that an optimal solution does not necessarily maximize the matching. Our model then results in a natural family-free genomic distance, that takes into consideration all given genes, without prior classification into families, and has a search space composed of matchings of any size. In spite of its bigger search space, our ILP seems to be boosted by a reduction of the number of co-optimal solutions due to the weights. Indeed, it converged faster than the original one by Bohnenkämper et al. for instances with the same number of multiple connections. We can handle not only bacterial genomes, but also fungi and insects, or sets of chromosomes of mammals and plants. In a comparison study of six fruit fly genomes, we obtained accurate results.
Rare disease patient matchmaking: development and outcomes of an internet case-finding strategy in the Undiagnosed Diseases Network
Authors: LeBlanc Kimberly , Glanton Emily , Nagy Anna , Bater Jorick , Berro Tala , McGuinness Molly A. , Studwell Courtney ,   Undiagnosed Diseases Network, Might Matthew
Published: May 2021

Background

Although clinician, researcher, and patient resources for matchmaking exist, finding similar patients remains an obstacle for rare disease diagnosis. The goals of this study were to develop and test the effectiveness of an Internet case-finding strategy and identify factors associated with increased matching within a rare disease population.

Methods

Public web pages were created for consented participants. Matches made, time to each inquiry and match, and outcomes were recorded and analyzed using descriptive statistics. A Poisson regression model was run to identify characteristics associated with matches.

Results

385 participants were referred to the project and 158 had pages posted. 579 inquiries were received; 89.0% were from the general public and 24.7% resulted in a match. 81.6% of pages received at least one inquiry and 15.0% had at least one patient match. Primary symptom category of neurology, diagnosis, gene page, and photo were associated with increased matches (p ≤ 0.05).

Conclusions

This Internet case-finding strategy was of interest to patients, families, and clinicians, and similar patients were identified using this approach. Extending matchmaking efforts to the general public resulted in matches and suggests including this population in matchmaking activities can improve identification of similar patients.
Validating online approaches for rare disease research using latent class mixture modeling
Authors: Dwyer Andrew A. , Zeng Ziwei , Lee Christopher S.
Published: May 2021

Background

Rare disease patients are geographically dispersed, posing challenges to research. Some researchers have partnered with patient organizations and used web-based approaches to overcome geographic recruitment barriers. Critics of such methods claim that samples are homogenous and do not represent the broader patient population—as patients recruited from patient organizations are thought to have high levels of needs. We applied latent class mixture modeling (LCMM) to define patient clusters based on underlying characteristics. We used previously collected data from a cohort of patients with congenital hypogonadotropic hypogonadism who were recruited online in collaboration with a patient organization. Patient demographics, clinical information, Revised Illness Perception Questionnaire (IPQ-R) scores and Zung self-rating depression Scale (SDS) were used as variables for LCMM analysis. Specifically, we aimed to test the classic critique that patients recruited online in collaboration with a patient organization are a homogenous group with high needs. We hypothesized that distinct classes (clinical profiles) of patients could be identified—thereby demonstrating the validity of online recruitment and supporting transferability of findings.

Results

In total, 154 patients with CHH were included. The LCMM analysis identified three distinct subgroups (Class I: n = 84 [54.5%], Class II: n = 41 [26.6%], Class III: n = 29 [18.8%]) that differed significantly in terms of age, education, disease consequences, emotional consequences, illness coherence and depression symptoms (all p < 0.001) as well as age at diagnosis (p = 0.045). Classes depict a continuum of psychosocial impact ranging from severe to relatively modest. Additional analyses revealed later diagnosis (Class I: 19.2 ± 6.7 years [95% CI 17.8–20.7]) is significantly associated with worse psychological adaptation and coping as assessed by disease consequences, emotional responses, making sense of one’s illness and SDS depressive symptoms (all p < 0.001).

Conclusions

We identify three distinct classes of patients who were recruited online in collaboration with a patient organization. Findings refute prior critiques of patient partnership and web-based recruitment for rare disease research. This is the first empirical data suggesting negative psychosocial sequelae of later diagnosis (“diagnostic odyssey”) often observed in CHH.
The impact of severe rare chronic neurological disease in childhood on the quality of life of families—a study on MLD and PCH2
Authors: Ammann-Schnell Louisa , Groeschel Samuel , Kehrer Christiane , Frölich Saskia , Krägeloh-Mann Ingeborg
Published: May 2021

Background

Rare and severe neurological disorders in childhood not only heavily affect the life perspective of the patients, but also their caregivers and families. The aim of this study was to investigate the impact of such diseases on the family, especially on the quality of life and life perspectives of parents, but also on the families’ everyday life, based on the model of two diseases which have been well described in recent years with respect to symptoms and course: metachromatic leukodystrophy (MLD) and pontocerebellar hypoplasia type 2 (PCH2). PCH2 is a primary severe developmental disorder, while children with MLD initially develop normally and then progressively deteriorate.

Methods

Using a semi-standardized questionnaire, 43 families with children suffering from MLD (n = 30) or PCH2 (n = 19) reported data on the severity of the illness/symptoms, on family support and the care situation, as well as on the circumstances of non-affected siblings and the parents’ work situation. In addition, the quality of life of parents and general family functioning was assessed using the PedsQL™ Family Impact Module [23]. Results for the latter were compared to published data from families with children without any chronic condition using student’s t-tests for independent samples. Potential factors influencing the PedsQL™ scores were analyzed using Spearman’s rank correlation.

Results

Parents of children with MLD and PCH2 reported significantly lower health-related quality of life (HRQOL) compared to parents of healthy children (P < 0.001). Mothers showed significantly poorer HRQOL (P < 0.05) and were significantly more dissatisfied with their professional development (P < 0.05) than fathers, and this was seen in relation to their child's disease. Neither the form of disease (‘primary’ symptomatic PCH2 or ‘secondary’ symptomatic MLD), nor the severity of the child’s illness (in terms of gross motor and speech function) had a specific impact on HRQOL in families. However, the time from diagnosis and advanced symptoms in the terminal disease stage were experienced as especially distressing.

Conclusions

This study illustrates that MLD and PCH2 affect mothers in particular, but also the entire family. This underlines the need for personalized care and counselling of parents and families, especially following diagnosis and during the end stage in a child with a severe, rare chronic neurological disorder.
Prospective study of the natural history of chronic acid sphingomyelinase deficiency in children and adults: eleven years of observation
Authors: McGovern Margaret M. , Wasserstein Melissa P. , Bembi Bruno , Giugliani Roberto , Mengel K. Eugen , Vanier Marie T. , Zhang Qi , Peterschmitt M. Judith
Published: May 2021

Background

Acid sphingomyelinase deficiency (ASMD) (also known as Niemann-Pick disease types A and B) is a rare and debilitating lysosomal storage disorder. This prospective, multi-center, multinational longitudinal study aimed to characterize the clinical features of chronic forms of ASMD and disease burden over time in children and adults.

Results

Fifty-nine patients (31 males/28 females) ranging in age from 7 to 64 years with chronic ASMD types A/B and B and at least two disease symptoms participated from 5 countries. Disease characteristics were assessed at baseline, after 1 year, and at the final visit (ranging from 4.5 to 11 years). Thirty patients (51%) were < 18 years at baseline (median age 12 years), and 29 were adults (median age 32 years). Overall, 32/59 patients completed the final visit, 9 died, 9 discontinued, and 9 were lost to follow up. Common clinical characteristics that tended to worsen gradually with time were splenomegaly, hepatomegaly, interstitial lung disease, lung diffusion capacity (DLCO), and dyslipidemia. Spleen volumes ranged from 4 to 29 multiples of normal at baseline, and splenomegaly was moderate or severe in 86%, 83%, and 90% of individuals at baseline, year 1, and final visits, respectively. The proportion of all individuals with interstitial lung disease was 66% (39/59) at baseline and 78% (25/32) at the final visit, while median % predicted DLCO decreased by > 10% from baseline to the final visit. Nine patients died (15%), eight of causes related to ASMD (most commonly pneumonia); of these eight patients, five (63%) had symptom onset at or before age 2. Overall, six of the nine deaths occurred before age 50 with three occurring before age 20. Individuals with either severe splenomegaly or prior splenectomy were ten times more likely to have died during the follow-up period than those with smaller or intact spleens (odds ratio 10.29, 95% CI 1.7, 62.7). Most children had growth deficits that persisted into adulthood.

Conclusions

This study provides important information about the natural history of chronic ASMD and provides a longitudinal view of the spectrum of disease manifestations and major morbidities in children and adults and supports the selection of clinically meaningful endpoints in therapeutic trials.
Genetic instability and anti-HPV immune response as drivers of infertility associated with HPV infection
Authors: Isaguliants Maria , Krasnyak Stepan , Smirnova Olga , Colonna Vincenza , Apolikhin Oleg , Buonaguro Franco M.
Published: May 2021

Human papillomavirus (HPV) is a sexually transmitted infection common among men and women of reproductive age worldwide. HPV viruses are associated with epithelial lesions and cancers. HPV infections have been shown to be significantly associated with many adverse effects in reproductive function. Infection with HPVs, specifically of high-oncogenic risk types (HR HPVs), affects different stages of human reproduction, resulting in a series of adverse outcomes: 1) reduction of male fertility (male infertility), characterized by qualitative and quantitative semen alterations; 2) impairment of couple fertility with increase of blastocyst apoptosis and reduction of endometrial implantation of trophoblastic cells; 3) defects of embryos and fetal development, with increase of spontaneous abortion and spontaneous preterm birth. The actual molecular mechanism(s) by which HPV infection is involved remain unclear. HPV-associated infertility as Janus, has two faces: one reflecting anti-HPV immunity, and the other, direct pathogenic effects of HPVs, specifically, of HR HPVs on the infected/HPV-replicating cells. Adverse effects observed for HR HPVs differ depending on the genotype of infecting virus, reflecting differential response of the host immune system as well as functional differences between HPVs and their individual proteins/antigens, including their ability to induce genetic instability/DNA damage. Review summarizes HPV involvement in all reproductive stages, evaluate the adverse role(s) played by HPVs, and identifies mechanisms of viral pathogenicity, common as well as specific for each stage of the reproduction process.