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Fulltext Prevention of soccer-related ankle injuries in youth amateur players: a randomized controlled trial

Ahmed F. Farhan, Stephany, Maria J., Shamil K. Mahammed

Movement Health & Exercise, 2017;6(1):39-45.
MyJurnal

In lower levels of play, the lateral ankle sprain is the most common injury, especially
amongst male youth soccer players. Purpose: The aim of the present study is to evaluate the effects
of an injury prevention program on the incidence of ankle injuries in male youth amateur players.
Study Design: Randomised controlled trial study. Methods: Fifty boys (mean ±SD: age 13.3±0.4
yr; body mass index of 20.9 ± 1.5 kg/m2
; stature: 1.6 ± 0.1 m) from two-sport schools, with 4.4 ±
0.5 years playing experience, participated. Players were randomly assigned to either an
experimental (EXP, n = 25) or a control (CON, n = 25) group. A physical exercise program
designed exclusively for youth male soccer players to educate as well as increasing the awareness
of the risk of injury of athletes and coaches. Over one year, all injuries were documented monthly
by physiotherapists. Complete monthly injury reports were available for 50 players. Results: Nine
ankle injuries occurred in the EXP group, and 20 injuries occurred in the CON group,
corresponding to incidence rates of 0.96 and 2.16, respectively, per 1000 player hours, which
equates to 55% fewer injuries in the EXP group. Conclusions: The incidence of ankle injuries
among youth male soccer players can be reduced by the implementation of a multifaceted, soccerspecific
physical exercise program. Coaches and players need better education regarding injury
prevention strategies and should include such interventions as part of their regular training.
Fulltext Health-related quality of life of COPD patients attending outpatient clinic at Institute of Respiratory Medicine, Kuala Lumpur, Malaysia

Maria, J., Aslinda, C.M., Nurul Ain, A.R., Fatim, T.M.

International Medical Journal Malaysia, 2010;9(1):9-13.
MyJurnal

Introduction: This study measured the health-related quality of life (HRQoL) among COPD patients attending outpatient clinic at Institute of Respiratory Medicine, Kuala Lumpur.
Materials and Methods: A cross sectional survey was conducted from November 2008 to January 2009 on 99 COPD patients. Subjects were interviewed through socio-demographic and health characteristics. The HRQoL was measured using the SF-36v2 questionnaires.
Results: Majority of the subjects were above 60 years (64.6%) with mean age of 64.10 ± 11.04 years, male (84.8%), Malays (49.5%), married (74.7%), primary educational level(57.6%), income level below RM1000 (39.4%), ex-smoker (64.6%), moderate COPD (40.4%), 1 to 5 years of illness (62.6%), presence of co-morbidities (65.7%) and satisfied with support from caregiver (48.5%). The total mean score for physical health component summary (PCS) was 41.64 ± 7.99 and mental health component summary (MCS) was 46.53 ± 13.21.
Conclusion: There were significant differences in PCS for different educational level (p<0.05) and socio-economic status (p<0.01). The MCS were signifi cantly different between ethnicity (p<0.05) and level of satisfaction with support from caregiver (p<0.01). This finding provides information that needed focus in
healthcare services.
KEYWORDS: COPD, health-related quality of life, Malaysia
Study site: outpatient clinic, Institute of Respiratory Medicine, Kuala Lumpur, Malaysia
Ethnicity and drug therapy for hypertension

Amudha K, Wong LP, Choy AM, Lang CC

Curr Pharm Des, 2003;9(21):1691-701.
PMID: 12871202

Physiological and pharmacological responses may be influenced by ethnicity as a result of genetic factors, environmental factors and/or their interaction. This review is divided into 2 parts. Firstly, there will be overview of ethnicity as a determinant of drug metabolism and response with reference to antihypertensive agents. The concept of ethnicity has been applied extensively to the study of hypertension especially in American blacks in whom the hypertension is more common and more aggressive. Thus, the second part of this review will then focus on examining the black-white differences in physiological responses to pharmacological challenge that may provide a link between these models and known ethnic differences in drug responses. We will discuss the hypertension studies that have examined the relative effectiveness of different classes of antihypertensive agents including several recent cardiovascular outcome trials that either have a high proportion of blacks or were conducted entirely in black subjects.
Fulltext Dietary zinc treatment for chronic copper intoxication in palm kernel cake (PKC) fed sheep

Hair-Bejo M, Alimon A, Maria J, Hass M, Moonafizad M

Malays J Nutr, 1996 Sep;2(2):196-206.
PMID: 22692141

Thirty, 4 month-old male Maim x Polled Dorset crossbred sheep were allocated into 6 groups of 5 animals each. Four groups of animals were stall-fed with basal diet of 90% palm kernel cake (PKC) and 10% grass (G) for 16 weeks. One group of the animal was slaughtered at the end of the 16 weeks feeding trial (PKC group), whilst the other three groups were further fed with either the same diet (PKC+PKC group) or fed with a new diet consisting of 30% corn and 10% fish meals (CF) and grass (60%) either with (PKC+CF+Zn group) or without (PKC+CF group) zinc supplementation (500 mg/g Zn as zinc sulfate) for another 16 weeks and were slaughtered at the end of the feeding trial, The other two groups which act as controls were fed with corn (30%) and fish meals (10%) and grass (60%), and were slaughtered at weeks 16 (CF group) and 32 (CF+CF group) of the trial. The blood, right and left liver, renal cortex and medulla, pancreas, bile and urine of all animals were analysed for copper and zinc contents using an atomic absorption spectrophotometer. The liver and kidney were also fixed in 10% buffered formalin for histopathological examination. The study showed that neither clinical signs nor gross lesions of copper or zinc toxicity were observed throughout the trial. However, the copper concentration in both the right and left liver of PKC fed sheep at weeks 16 and 32 rose to about 3 times that of the controls and remained high in both the PKC+CF and PKC+CF+Zn groups. A similar pattern of copper concentration was observed in the blood. The copper and zinc contents in the renal cortex and medulla, pancreas, bile and urine remained low in all groups. The zinc content in the liver of PKC+CF+Zn group was significantly increased. Histologically, moderate hepatic lesions were observed in the PKC fed sheep at week 32. The lesions were milder in the other groups especially in the PKC+CF+Zn group. No significant renal lesions was recorded in all groups. It was concluded that the usage of dietary zinc supplementation (500 mg/g) in the treatment of PKC toxicity in sheep was unsatisfactory. The ability of Malin x Polled Dorset crossbred sheep to tolerate the high copper content in PKC at least during the first 16 weeks of the feeding trial may provide more avenue in the utilization of PKC as a major feed ingredient in sheep.
Fulltext Isolation of Mycoplasma hyosynoviae from pneumonic lung of swine

Dahlia H, Tan LJ, Zarrahimah Z, Maria J

Trop Biomed, 2009 Dec;26(3):341-5.
PMID: 20237449 MyJurnal

The isolation of Mycoplasma hyosynoviae from a piglet with severe pneumonia is described. This is the first report of M. hyosynoviae isolation in the country. The lung sample where the isolation was made was severely consolidated, suppurative and pleurisy. The pathogenicity of the M. hyosynoviae isolated has yet to be determined.
Combination of drugs acting on the natriuretic system and the renin-angiotensin system in heart failure

Chee KH, Amudha K, Hussain NA, Haizal HK, Choy AM, Lang CC

J Renin Angiotensin Aldosterone Syst, 2003 Sep;4(3):140-8.
PMID: 14608517

Conventional diuretic agents are very effective agents in relieving volume overload and congestive symptoms in chronic heart failure (CHF). However, they are associated with activation of the renin-angiotensin system (RAS) and the sympathetic nervous system and a reduction in glomerular filtration rate, all of which have been associated with adverse outcomes in CHF. Therefore, there is an increasing interest in drugs that target the natriuretic system without neurohormonal activation and deterioration of renal function. In this review, we will discuss the underlying rationale and evidence behind currently pursued strategies that target the natriuretic system. This includes the administration of natriuretic peptides (NPs) and strategies that potentiate the NP system, such as neutral endopeptidase inhibition. We will also highlight some potentially important interactions of these strategies with drugs that target the RAS.
Fulltext High-risk human papillomavirus viral load and persistence among heterosexual HIV-negative and HIV-positive men

Grabowski MK, Gray RH, Serwadda D, Kigozi G, Gravitt PE, Nalugoda F, et al.

Sex Transm Infect, 2014 Jun;90(4):337-43.
PMID: 24482488 DOI: 10.1136/sextrans-2013-051230

OBJECTIVES: High-risk human papillomavirus (HR-HPV) viral load is associated with HR-HPV transmission and HR-HPV persistence in women. It is unknown whether HR-HPV viral load is associated with persistence in HIV-negative or HIV-positive men.
METHODS: HR-HPV viral load and persistence were evaluated among 703 HIV-negative and 233 HIV-positive heterosexual men who participated in a male circumcision trial in Rakai, Uganda. Penile swabs were tested at baseline and 6, 12 and 24 months for HR-HPV using the Roche HPV Linear Array, which provides a semiquantitative measure of HPV shedding by hybridisation band intensity (graded: 1-4). Prevalence risk ratios (PRR) were used to estimate the association between HR-HPV viral load and persistent detection of HR-HPV.
RESULTS: HR-HPV genotypes with high viral load (grade:3-4) at baseline were more likely to persist than HR-HPV genotypes with low viral load (grade: 1-2) among HIV-negative men (month 6: adjPRR=1.83, 95% CI 1.32 to 2.52; month 12: adjPRR=2.01, 95% CI 1.42 to 3.11), and HIV-positive men (month 6: adjPRR=1.33, 95% CI 1.06 to 1.67; month 12: adjPRR=1.73, 95% CI 1.18 to 2.54). Long-term persistence of HR-HPV was more frequent among HIV-positive men compared with HIV-negative men (month 24: adjPRR=2.27, 95% CI 1.47 to 3.51). Persistence of newly detected HR-HPV at the 6-month and 12-month visits with high viral load were also more likely to persist to 24 months than HR-HPV with low viral load among HIV-negative men (adjPRR=1.67, 95% CI 0.88 to 3.16).
CONCLUSIONS: HR-HPV genotypes with high viral load are more likely to persist among HIV-negative and HIV-positive men, though persistence was more common among HIV-positive men overall. The results may explain the association between high HR-HPV viral load and HR-HPV transmission.
Nanotechnology-based drug delivery systems for Alzheimer's disease management: Technical, industrial, and clinical challenges

Wen MM, El-Salamouni NS, El-Refaie WM, Hazzah HA, Ali MM, Tosi G, et al.

J Control Release, 2017 01 10;245:95-107.
PMID: 27889394 DOI: 10.1016/j.jconrel.2016.11.025

Alzheimer's disease (AD) is a neurodegenerative disease with high prevalence in the rapidly growing elderly population in the developing world. The currently FDA approved drugs for the management of symptomatology of AD are marketed mainly as conventional oral medications. Due to their gastrointestinal side effects and lack of brain targeting, these drugs and dosage regiments hinder patient compliance and lead to treatment discontinuation. Nanotechnology-based drug delivery systems (NTDDS) administered by different routes can be considered as promising tools to improve patient compliance and achieve better therapeutic outcomes. Despite extensive research, literature screening revealed that clinical activities involving NTDDS application in research for AD are lagging compared to NTDDS for other diseases such as cancers. The industrial perspectives, processability, and cost/benefit ratio of using NTDDS for AD treatment are usually overlooked. Moreover, active and passive immunization against AD are by far the mostly studied alternative AD therapies because conventional oral drug therapy is not yielding satisfactorily results. NTDDS of approved drugs appear promising to transform this research from 'paper to clinic' and raise hope for AD sufferers and their caretakers. This review summarizes the recent studies conducted on NTDDS for AD treatment, with a primary focus on the industrial perspectives and processability. Additionally, it highlights the ongoing clinical trials for AD management.
Fulltext Capsular serotyping of Pasteurella multocida from various animal hosts - a comparison of phenotypic and genotypic methods

Arumugam ND, Ajam N, Blackall PJ, Asiah NM, Ramlan M, Maria J, et al.

Trop Biomed, 2011 Apr;28(1):55-63.
PMID: 21602769

One hundred and fourteen strains of Pasteurella multocida were isolated from different domestic animals species (cattle, buffalo, sheep, goat, pig, rabbit, dog, cat), avian species (chicken, duck, turkey) and wild animals (deer, tiger, orang utan, marmoset). The serogroups of P. multocida were determined by both conventional capsular serotyping and a multiplex PCR assay targeting specific capsular genes. Based on the conventional serotyping method, the 114 strains of P. multocida were subtyped into 55 species-specific (untypeable strains) P. multocida, 15 serogroup A, 23 serogroup B and 21 serogroup D. Based on the multiplex PCR assay on the specific capsular genes associated with each serogroup, the 114 strains were further divided to 22 species-specific P. multocida (KMT1 - 460 bp), 53 serogroup A (A - 1,044 bp), 33 serogroup B (B - 760 bp) and 6 serogroup D (D - 657 bp). No serogroup E (511 bp) or F (851 bp) was detected among the Malaysian P. multocida. PCR-based typing was more discriminative and could further subtype the previously untypeable strains. Overall, there was a significant and positive correlation between both methods in serogrouping P. multocida (r = 0.7935; p<0.4893). Various serogroups of P. multocida were present among the livestock with 75% of the strains belonging to serogroups A or B. PCR serotyping was therefore a highly species-specific, sensitive and robust method for detection and differentiation of P. multocida serogroups compared to conventional serotyping. To the best of our knowledge, this is the first report from Malaysia of the application of a PCR to rapidly define the species-specific P. multocida and its serogroups as an important zoonotic pathogen in Malaysia.
Fulltext A Global Survey of Hypervirulent Aeromonas hydrophila (vAh) Identified vAh Strains in the Lower Mekong River Basin and Diverse Opportunistic Pathogens from Farmed Fish and Other Environmental Sources

Xu T, Rasmussen-Ivey CR, Moen FS, Fernández-Bravo A, Lamy B, Beaz-Hidalgo R, et al.

Microbiol Spectr, 2023 Feb 23;11(2):e0370522.
PMID: 36815836 DOI: 10.1128/spectrum.03705-22

Hypervirulent Aeromonas hydrophila (vAh) has emerged as the etiologic agent of epidemic outbreaks of motile Aeromonas septicemia (MAS) in high-density aquaculture of farmed carp in China and catfish in the United States, which has caused millions of tons of lost fish. We conducted a global survey to better understand the evolution, geographical distribution, and phylogeny of vAh. Aeromonas isolates were isolated from fish that showed clinical symptoms of MAS, and pure cultures were screened for the ability to utilize myo-inositol as the sole carbon source. A total of 113 myo-inositol-utilizing bacterial strains were included in this study, including additional strains obtained from previously published culture collections. Based on a gyrB phylogeny, this collection included 66 A. hydrophila isolates, 48 of which were vAh. This collection also included five new vAh isolates from diseased Pangas catfish (Pangasius pangasius) and striped catfish (Pangasianodon hypophthalmus) obtained in Cambodia and Vietnam, respectively. Genome sequences were generated from representative vAh and non-vAh isolates to evaluate the potential for lateral genetic transfer of the myo-inositol catabolism pathway. Phylogenetic analyses of each of the nine genes required for myo-inositol utilization revealed the close affiliation of vAh strains regardless of geographic origin and suggested lateral genetic transfer of this catabolic pathway from an Enterobacter species. Prediction of virulence factors was conducted to determine differences between vAh and non-vAh strains in terms of virulence and secretion systems. Core genome phylogenetic analyses on vAh isolates and Aeromonas spp. disease isolates (55 in total) were conducted to evaluate the evolutionary relationships among vAh and other Aeromonas sp. isolates, which supported the clonal nature of vAh isolates. IMPORTANCE This global survey of vAh brought together scientists that study fish disease to evaluate the evolution, geographical distribution, phylogeny, and hosts of vAh and other Aeromonas sp. isolates. In addition to vAh isolates from China and the United States, four new vAh isolates were isolated from the lower Mekong River basin in Cambodia and Vietnam, indicating the significant threat of vAh to modern aquaculture and the need for improved biosecurity to prevent vAh spread.
Global guideline for the diagnosis and management of the endemic mycoses: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology

Thompson GR, Le T, Chindamporn A, Kauffman CA, Alastruey-Izquierdo A, Ampel NM, et al.

Lancet Infect Dis, 2021 12;21(12):e364-e374.
PMID: 34364529 DOI: 10.1016/S1473-3099(21)00191-2

The global burden of the endemic mycoses (blastomycosis, coccidioidomycosis, emergomycosis, histoplasmosis, paracoccidioidomycosis, sporotrichosis, and talaromycosis) continues to rise yearly and these infectious diseases remain a leading cause of patient morbidity and mortality worldwide. Management of the associated pathogens requires a thorough understanding of the epidemiology, risk factors, diagnostic methods and performance characteristics in different patient populations, and treatment options unique to each infection. Guidance on the management of these infections has the potential to improve prognosis. The recommendations outlined in this Review are part of the "One World, One Guideline" initiative of the European Confederation of Medical Mycology. Experts from 23 countries contributed to the development of these guidelines. The aim of this Review is to provide an up-to-date consensus and practical guidance in clinical decision making, by engaging physicians and scientists involved in various aspects of clinical management.
Fulltext A standardised model for stool banking for faecal microbiota transplantation: a consensus report from a multidisciplinary UEG working group

Keller JJ, Ooijevaar RE, Hvas CL, Terveer EM, Lieberknecht SC, Högenauer C, et al.

United European Gastroenterol J, 2021 Mar;9(2):229-247.
PMID: 33151137 DOI: 10.1177/2050640620967898

BACKGROUND: Faecal microbiota transplantation is an emerging therapeutic option, particularly for the treatment of recurrent Clostridioides difficile infection. Stool banks that organise recruitment and screening of faeces donors are being embedded within the regulatory frameworks described in the European Union Tissue and Cells Directive and the technical guide to the quality and safety of tissue and cells for human application, published by the European Council.
OBJECTIVE: Several European and international consensus statements concerning faecal microbiota transplantation have been issued. While these documents provide overall guidance, we aim to provide a detailed description of all processes that relate to the collection, handling and clinical application of human donor stool in this document.
METHODS: Collaborative subgroups of experts on stool banking drafted concepts for all domains pertaining to stool banking. During a working group meeting in the United European Gastroenterology Week 2019 in Barcelona, these concepts were discussed and finalised to be included in our overall guidance document about faecal microbiota transplantation.
RESULTS: A guidance document for all domains pertaining to stool banking was created. This document includes standard operating manuals for several processes involved with stool banking, such as handling of donor material, storage and donor screening.
CONCLUSION: The implementation of faecal microbiota transplantation by stool banks in concordance with our guidance document will enable quality assurance and guarantee the availability of donor faeces preparations for patients.
Fulltext Prediagnostic Plasma Bile Acid Levels and Colon Cancer Risk: A Prospective Study

Kühn T, Stepien M, López-Nogueroles M, Damms-Machado A, Sookthai D, Johnson T, et al.

J Natl Cancer Inst, 2020 May 01;112(5):516-524.
PMID: 31435679 DOI: 10.1093/jnci/djz166

BACKGROUND: Bile acids have been proposed to promote colon carcinogenesis. However, there are limited prospective data on circulating bile acid levels and colon cancer risk in humans.
METHODS: Associations between prediagnostic plasma levels of 17 primary, secondary, and tertiary bile acid metabolites (conjugated and unconjugated) and colon cancer risk were evaluated in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Bile acid levels were quantified by tandem mass spectrometry in samples from 569 incident colon cancer cases and 569 matched controls. Multivariable logistic regression analyses were used to estimate odds ratios (ORs) for colon cancer risk across quartiles of bile acid concentrations.
RESULTS: Positive associations were observed between colon cancer risk and plasma levels of seven conjugated bile acid metabolites: the primary bile acids glycocholic acid (ORquartile 4 vs quartile 1= 2.22, 95% confidence interval [CI] = 1.52 to 3.26), taurocholic acid (OR = 1.78, 95% CI = 1.23 to 2.58), glycochenodeoxycholic acid (OR = 1.68, 95% CI = 1.13 to 2.48), taurochenodeoxycholic acid (OR = 1.62, 95% CI = 1.11 to 2.36), and glycohyocholic acid (OR = 1.65, 95% CI = 1.13 to 2.40), and the secondary bile acids glycodeoxycholic acid (OR = 1.68, 95% CI = 1.12 to 2.54) and taurodeoxycholic acid (OR = 1.54, 95% CI = 1.02 to 2.31). By contrast, unconjugated bile acids and tertiary bile acids were not associated with risk.
CONCLUSIONS: This prospective study showed that prediagnostic levels of certain conjugated primary and secondary bile acids were positively associated with risk of colon cancer. Our findings support experimental data to suggest that a high bile acid load is colon cancer promotive.
Fulltext Exogenous hormone use and cutaneous melanoma risk in women: The European Prospective Investigation into Cancer and Nutrition

Cervenka I, Al Rahmoun M, Mahamat-Saleh Y, Fournier A, Boutron-Ruault MC, Severi G, et al.

Int J Cancer, 2020 Jun 15;146(12):3267-3280.
PMID: 31506954 DOI: 10.1002/ijc.32674

Evidence suggests an influence of sex hormones on cutaneous melanoma risk, but epidemiologic findings are conflicting. We examined the associations between use of oral contraceptives (OCs) and menopausal hormone therapy (MHT) and melanoma risk in women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Information on exogenous hormone use at baseline was derived from country-specific self-administered questionnaires. We used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over 1992-2015, 1,696 melanoma cases were identified among 334,483 women, whereof 770 cases among 134,758 postmenopausal women. There was a positive, borderline-significant association between OC use and melanoma risk (HR = 1.12, 95% CI = 1.00-1.26), with no detected heterogeneity across countries (phomogeneity = 0.42). This risk increased linearly with duration of use (ptrend = 0.01). Among postmenopausal women, ever use of MHT was associated with a nonsignificant increase in melanoma risk overall (HR = 1.14, 95% CI = 0.97-1.43), which was heterogeneous across countries (phomogeneity = 0.05). Our findings do not support a strong and direct association between exogenous hormone use and melanoma risk. In order to better understand these relations, further research should be performed using prospectively collected data including detailed information on types of hormone, and on sun exposure, which may act as an important confounder or effect modifier on these relations.
Frequency and Characterization of Movement Disorders in Anti-IgLON5 Disease

Gaig C, Compta Y, Heidbreder A, Marti MJ, Titulaer MJ, Crijnen Y, et al.

Neurology, 2021 Aug 11.
PMID: 34380749 DOI: 10.1212/WNL.0000000000012639

OBJECTIVE: Anti-IgLON5 disease is a recently described neurological disease that shares features of autoimmunity and neurodegeneration. Abnormal movements appear to be frequent and important but have not been characterized and are under-reported. Here we describe the frequency and types of movement disorders in a series of consecutive patients with this disease.
METHODS: In this retrospective, observational study, the presence and phenomenology of movement disorders were assessed with a standardized clinical questionnaire. Available videos were centrally reviewed by three experts in movement disorders.
RESULTS: Seventy two patients were included. In 41 (57%) the main reason for initial consultation was difficulty walking along with one or several concurrent movement disorders. At the time of anti-IgLON5 diagnosis, 63 (87%) patients had at least one movement disorder with a median of three per patient. The most frequent abnormal movements were gait and balance disturbances (52 patients, 72%), chorea (24, 33%), bradykinesia (20, 28%), dystonia (19, 26%), abnormal body postures or rigidity (18, 25%), and tremor (15, 21%). Other hyperkinetic movements (myoclonus, akathisia, myorhythmia, myokymia, or abdominal dyskinesias) occurred in 26 (36%) patients. The craniofacial region was one of the most frequently affected by multiple concurrent movement disorders (23 patients, 32%) including dystonia (13), myorhythmia (6), chorea (4) or myokymia (4). Considering any body region, the most frequent combination of multiple movement disorders consisted of gait instability or ataxia associated with craniofacial dyskinesias or generalized chorea observed in 31(43%) of patients. In addition to abnormal movements, 87% of patients had sleep alterations, 74% bulbar dysfunction, and 53% cognitive impairment. Fifty-five (76%) patients were treated with immunotherapy, resulting in important and sustained improvement of the movement disorders in only seven (13%) cases.
CONCLUSIONS: Movement disorders are a frequent and leading cause of initial neurological consultation in patients with anti-IgLON5 disease. Although multiple types of abnormal movements can occur, the most prevalent are disorders of gait, generalized chorea, and dystonia and other dyskinesias that frequently affect craniofacial muscles. Overall, anti-IgLON5 disease should be considered in patients with multiple movement disorders, particularly if they occur in association with sleep alterations, bulbar dysfunction, or cognitive impairment.
Fulltext Rationale and design of the PeriOperative ISchemic Evaluation-3 (POISE-3): a randomized controlled trial evaluating tranexamic acid and a strategy to minimize hypotension in noncardiac surgery

Marcucci M, Painter TW, Conen D, Leslie K, Lomivorotov VV, Sessler D, et al.

Trials, 2022 Jan 31;23(1):101.
PMID: 35101083 DOI: 10.1186/s13063-021-05992-1

BACKGROUND: For patients undergoing noncardiac surgery, bleeding and hypotension are frequent and associated with increased mortality and cardiovascular complications. Tranexamic acid (TXA) is an antifibrinolytic agent with the potential to reduce surgical bleeding; however, there is uncertainty about its efficacy and safety in noncardiac surgery. Although usual perioperative care is commonly consistent with a hypertension-avoidance strategy (i.e., most patients continue their antihypertensive medications throughout the perioperative period and intraoperative mean arterial pressures of 60 mmHg are commonly accepted), a hypotension-avoidance strategy may improve perioperative outcomes.
METHODS: The PeriOperative Ischemic Evaluation (POISE)-3 Trial is a large international randomized controlled trial designed to determine if TXA is superior to placebo for the composite outcome of life-threatening, major, and critical organ bleeding, and non-inferior to placebo for the occurrence of major arterial and venous thrombotic events, at 30 days after randomization. Using a partial factorial design, POISE-3 will additionally determine the effect of a hypotension-avoidance strategy versus a hypertension-avoidance strategy on the risk of major cardiovascular events, at 30 days after randomization. The target sample size is 10,000 participants. Patients ≥45 years of age undergoing noncardiac surgery, with or at risk of cardiovascular and bleeding complications, are randomized to receive a TXA 1 g intravenous bolus or matching placebo at the start and at the end of surgery. Patients, health care providers, data collectors, outcome adjudicators, and investigators are blinded to the treatment allocation. Patients on ≥ 1 chronic antihypertensive medication are also randomized to either of the two blood pressure management strategies, which differ in the management of patient antihypertensive medications on the morning of surgery and on the first 2 days after surgery, and in the target mean arterial pressure during surgery. Outcome adjudicators are blinded to the blood pressure treatment allocation. Patients are followed up at 30 days and 1 year after randomization.
DISCUSSION: Bleeding and hypotension in noncardiac surgery are common and have a substantial impact on patient prognosis. The POISE-3 trial will evaluate two interventions to determine their impact on bleeding, cardiovascular complications, and mortality.
TRIAL REGISTRATION: ClinicalTrials.gov NCT03505723. Registered on 23 April 2018.
Fulltext Concepts for the development of person-centred, digitally-enabled, Artificial Intelligence-assisted ARIA care pathways (ARIA 2024)

Bousquet J, Schünemann HJ, Sousa-Pinto B, Zuberbier T, Togias A, Samolinski B, et al.

J Allergy Clin Immunol Pract, 2024 Jul 04.
PMID: 38971567 DOI: 10.1016/j.jaip.2024.06.040

The traditional healthcare model is focused on diseases (medicine and natural science) and does not acknowledge patients' resources and abilities to be experts in their own life based on their lived experiences. Improving healthcare safety, quality and coordination, as well as quality of life, are important aims in the care of patients with chronic conditions. Person-centred care needs to ensure that people's values and preferences guide clinical decisions. This paper reviews current knowledge to develop (i) digital care pathways for rhinitis and asthma multimorbidity and (ii) digitally-enabled person-centred care (1). It combines all relevant research evidence, including the so-called real-world evidence, with the ultimate goal to develop digitally-enabled, patient-centred care. The paper includes (i) Allergic Rhinitis and its Impact on Asthma (ARIA), a two-decade journey, (ii) Grading of Recommendations, Assessment, Development and Evaluation (GRADE), the evidence-based model of guidelines in airway diseases, (iii) mHealth impact on airway diseases, (iv) from guidelines to digital care pathways, (v) embedding Planetary Health, (vi) novel classification of rhinitis and asthma, (vi) embedding real-life data with population-based studies, (vii) the ARIA-EAACI strategy for the management of airway diseases using digital biomarkers, (viii) Artificial Intelligence, (ix) the development of digitally-enabled ARIA Person-Centred Care and (x) the political agenda. The ultimate goal is to propose ARIA 2024 guidelines centred around the patient in order to make them more applicable and sustainable.
Fulltext Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine

Tobias DK, Merino J, Ahmad A, Aiken C, Benham JL, Bodhini D, et al.

Nat Med, 2023 Oct;29(10):2438-2457.
PMID: 37794253 DOI: 10.1038/s41591-023-02502-5

Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
Fulltext Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1

Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, et al.

Autophagy, 2021 Jan;17(1):1-382.
PMID: 33634751 DOI: 10.1080/15548627.2020.1797280

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

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