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1.
Phys Chem Chem Phys ; 26(21): 15156-15180, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38747576

ABSTRACT

The extension of conceptual density-functional theory (conceptual DFT) to include external electromagnetic fields in chemical systems is utilised to investigate the effects of strong magnetic fields on the electronic charge distribution and its consequences on the reactivity of π-systems. Formaldehyde, H2CO, is considered as a prototypical example and current-density-functional theory (current-DFT) calculations are used to evaluate the electric dipole moment together with two principal local conceptual DFT descriptors, the electron density and the Fukui functions, which provide insight into how H2CO behaves chemically in a magnetic field. In particular, the symmetry properties of these quantities are analysed on the basis of group, representation, and corepresentation theories using a recently developed automatic program for symbolic symmetry analysis, QSYM2. This allows us to leverage the simple symmetry constraints on the macroscopic electric dipole moment components to make profound predictions on the more nuanced symmetry transformation properties of the microscopic frontier molecular orbitals (MOs), electron densities, and Fukui functions. This is especially useful for complex-valued MOs in magnetic fields whose detailed symmetry analyses lead us to define the new concepts of modular and phasal symmetry breaking. Through these concepts, the deep connection between the vanishing constraints on the electric dipole moment components and the symmetry of electron densities and Fukui functions can be formalised, and the inability of the magnetic field in all three principal orientations considered to induce asymmetry with respect to the molecular plane of H2CO can be understood from a molecular perspective. Furthermore, the detailed forms of the Fukui functions reveal a remarkable reversal in the direction of the dipole moment along the CO bond in the presence of a parallel or perpendicular magnetic field, the origin of which can be attributed to the mixing between the frontier MOs due to their subduced symmetries in magnetic fields. The findings in this work are also discussed in the wider context of a long-standing debate on the possibility to create enantioselectivity by external fields.

2.
Nat Commun ; 15(1): 326, 2024 Jan 06.
Article in English | MEDLINE | ID: mdl-38182626

ABSTRACT

Fine-scale knowledge of the changes in composition and function of the human gut microbiome compared that of our closest relatives is critical for understanding the evolutionary processes underlying its developmental trajectory. To infer taxonomic and functional changes in the gut microbiome across hominids at different timescales, we perform high-resolution metagenomic-based analyzes of the fecal microbiome from over two hundred samples including diverse human populations, as well as wild-living chimpanzees, bonobos, and gorillas. We find human-associated taxa depleted within non-human apes and patterns of host-specific gut microbiota, suggesting the widespread acquisition of novel microbial clades along the evolutionary divergence of hosts. In contrast, we reveal multiple lines of evidence for a pervasive loss of diversity in human populations in correlation with a high Human Development Index, including evolutionarily conserved clades. Similarly, patterns of co-phylogeny between microbes and hosts are found to be disrupted in humans. Together with identifying individual microbial taxa and functional adaptations that correlate to host phylogeny, these findings offer insights into specific candidates playing a role in the diverging trajectories of the gut microbiome of hominids. We find that repeated horizontal gene transfer and gene loss, as well as the adaptation to transient microaerobic conditions appear to have played a role in the evolution of the human gut microbiome.


Subject(s)
Gastrointestinal Microbiome , Hominidae , Microbiota , Animals , Gastrointestinal Microbiome/genetics , Pan troglodytes , Pan paniscus
3.
J Chem Theory Comput ; 20(1): 114-133, 2024 Jan 09.
Article in English | MEDLINE | ID: mdl-38145888

ABSTRACT

Symmetry provides a powerful machinery to classify, interpret, and understand quantum-mechanical theories and results. However, most contemporary quantum chemistry packages lack the ability to handle degeneracy and symmetry breaking effects, especially in non-Abelian groups, and they are not able to characterize symmetry in the presence of external magnetic or electric fields. In this article, a program written in Rust entitled QSym2 that makes use of group and representation theories to provide symmetry analysis for a wide range of quantum-chemical calculations is introduced. With its ability to generate character tables symbolically on-the-fly and by making use of a generic symmetry-orbit-based representation analysis method formulated in this work, QSym2 is able to address all of these shortcomings. To illustrate these capabilities of QSym2, four sets of case studies are examined in detail in this article: (i) high-symmetry C84H64, C60, and B9- to demonstrate the analysis of degenerate molecular orbitals (MOs); (ii) octahedral Fe(CN)63- to demonstrate the analysis of symmetry-broken determinants and MOs; (iii) linear hydrogen fluoride in a magnetic field to demonstrate the analysis of magnetic symmetry; and (iv) equilateral H3+ to demonstrate the analysis of density symmetries.

4.
Clin Exp Dermatol ; 46(8): 1504-1510, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34081799

ABSTRACT

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, various adverse skin reactions to long-term mask wearing have been reported. AIM: To assess the clinical features of mask-induced dermatoses and to recommend prevention and treatment options. METHODS: From April to August 2020, questionnaires including topics such as demographic information, pre-existing skin disorders, reported mask-related symptoms, daily mask-wearing duration and frequency, types of masks used and whether the participant was a healthcare worker, were distributed to patients in 12 hospitals. Dermatologists assessed skin lesions, confirmed diagnosis and recorded treatments. RESULTS: Itchiness was the most frequent symptom, mostly affecting the cheeks. The most common skin disease was new-onset contact dermatitis (33.94%), followed by new-onset acne (16.97%) and worsening of pre-existing acne (16.97%). Daily wearing of masks was significantly (P = 0.02) associated with new-onset contact dermatitis. More than half of patients with pre-existing skin problems experienced disease worsening while wearing masks. Longer duration of wearing (> 6 h/day, P = 0.04) and use of cotton masks (P < 0.001) significantly increased acne flare-up. Healthcare workers had a higher incidence of skin disease. Skin lesions were generally mild and well tolerated with topical treatment. The study had some limitations: the effect of seasonal characteristics and other risk factors were not assessed, and the patients were visiting dermatological clinics and had interest in their skin status, thus, there may have been selection bias. CONCLUSION: Mask-induced/-triggered dermatoses contribute to increase the dermatological burden during the pandemic.


Subject(s)
Dermatitis, Occupational/etiology , Facial Dermatoses/etiology , Masks/adverse effects , Personnel, Hospital , Acne Vulgaris/etiology , Adult , COVID-19/prevention & control , Female , Hospitals, University , Humans , Male , Middle Aged , Pandemics/prevention & control , Pruritus/etiology , Republic of Korea , SARS-CoV-2 , Tertiary Care Centers
5.
Br J Dermatol ; 185(3): 573-584, 2021 09.
Article in English | MEDLINE | ID: mdl-33733457

ABSTRACT

BACKGROUND: The human skin offers diverse ecosystems for microbial symbionts. However, the factors shaping skin-microbiome interactions are still insufficiently characterized. This contrasts with the broader knowledge about factors influencing gut microbiota. OBJECTIVES: We aimed to investigate major patterns of association of host traits, lifestyle and environmental factors with skin bacteria in two German populations. METHODS: This is a cross-sectional study with 647 participants from two population-based German cohorts, PopGen (n = 294) and KORA FF4 (n = 353), totalling 1794 skin samples. The V1-V2 regions of the 16S ribosomal RNA (rRNA) gene were sequenced. Associations were tested with two bacterial levels, community (beta diversity) and 16S rRNA gene amplicon sequence variants (ASVs). RESULTS: We validated known associations of the skin microbiota with skin microenvironment, age, body mass index and sex. These factors were associated with beta diversity and abundance of ASVs in PopGen, which was largely replicated in KORA FF4. Most intriguingly, dietary macronutrients and total dietary energy were associated with several ASVs. ASVs were also associated with smoking, alcohol consumption, skin pH, skin type, transepidermal water loss, education and several environmental exposures, including hours spent outdoors. Associated ASVs included members of the genera Propionibacterium, Corynebacterium and Staphylococcus. CONCLUSIONS: We expand the current understanding of factors associated with the skin bacterial community. We show the association of diet with skin bacteria. Finally, we hypothesize that the skin microenvironment and host physiology would shape the skin bacterial community to a greater extent compared with a single skin physiological feature, lifestyle and environmental exposure.


Subject(s)
Bacteria , Microbiota , Bacteria/genetics , Cross-Sectional Studies , Humans , Life Style , Microbiota/genetics , RNA, Ribosomal, 16S/genetics
6.
Osteoporos Int ; 32(3): 529-538, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33151377

ABSTRACT

A total of 25,306 psoriasis participants were matched to 101,224 controls, and the occurrence of osteoporosis was analyzed. Additionally, 79,212 osteoporosis patients were matched to 79,212 controls and a previous history of psoriasis was analyzed. Psoriasis increased the risk of osteoporosis among participants aged ≥ 40 years. INTRODUCTION: The aim of the present study was to evaluate the association between psoriasis and osteoporosis using two different studies. METHODS: Data from the Korean National Health Insurance Service-Health Screening Cohort of participants aged ≥ 40 years were collected from 2002 to 2013. Psoriasis and osteoporosis were included using International Classification of Diseases (ICD)-10 codes. In study I (a follow-up study), a total of 25,306 psoriasis participants were matched to 101,224 controls with respect to age, sex, income, and region of residence, and the occurrence of osteoporosis was analyzed. Crude (simple) and adjusted hazard ratios (HRs) were analyzed using a stratified Cox proportional hazard model. In study II (a nested case-control study), a total of 79,212 osteoporosis patients were matched to 79,212 controls and a previous history of psoriasis was analyzed. Crude and adjusted odds ratios (ORs) were analyzed using a conditional logistic regression analysis. Subgroup analyses were conducted according to age group and sex. RESULTS: The adjusted HR of osteoporosis was 1.09 (95% confidence interval [CI] = 1.05-1.13, P < 0.001) in study I. In the subgroup analysis according to age and sex, the results were consistent except for ≥ 60-year-old women. The adjusted OR of psoriasis was 1.21 (95% CI = 1.16-1.27, P < 0.001) in study II. All subgroups demonstrated high adjusted ORs of osteoporosis for psoriasis. CONCLUSIONS: Psoriasis increased the risk of osteoporosis among participants aged ≥ 40 years in Korea.


Subject(s)
Osteoporosis , Psoriasis , Aged , Case-Control Studies , Female , Follow-Up Studies , Humans , Longitudinal Studies , Middle Aged , Osteoporosis/epidemiology , Osteoporosis/etiology , Psoriasis/complications , Psoriasis/epidemiology , Republic of Korea/epidemiology , Risk Factors
7.
J Eur Acad Dermatol Venereol ; 35(3): 669-676, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33037671

ABSTRACT

BACKGROUND: The Breslow depth is an important parameter to determine the excision margin and prognosis of melanoma. However, it is difficult to accurately determine the actual Breslow depth before surgery using the existing ocular micrometer and biopsy technique. OBJECTIVES: To evaluate the use of 3D wide-field multispectral photoacoustic imaging to non-invasively measure depth and outline the boundary of melanomas for optimal surgical margin selection. METHODS: Six melanoma patients were examined in vivo using the 3D multispectral photoacoustic imaging system. For five cases of melanomas (one in situ, three nodular, and one acral lentiginous type melanoma), the spectrally unmixed photoacoustic depths were calculated and compared against histopathological depths. RESULTS: Spectrally unmixed photoacoustic depths and histopathological depths match well within a mean absolute error of 0.36 mm. In particular, the measured minimum and maximum depths in the in situ and nodular type of melanoma were 0.6 and 9.1 mm, respectively. In the 3D photoacoustic image of one metastatic melanoma, feeding vessels were visualized in the melanoma, suggesting the neovascularization around the tumour. CONCLUSIONS: The 3D multispectral photoacoustic imaging not only provides well-measured depth and sizes of various types of melanomas, it also visualizes the metastatic type of melanoma. Obtaining accurate depth and boundary information of melanoma before surgery would play a useful role in the complete excision of melanoma during surgery.


Subject(s)
Melanoma , Photoacoustic Techniques , Skin Neoplasms , Diagnostic Imaging , Humans , Melanoma/diagnostic imaging , Pilot Projects , Skin Neoplasms/diagnostic imaging
8.
J Chem Theory Comput ; 16(2): 904-930, 2020 Feb 11.
Article in English | MEDLINE | ID: mdl-31820967

ABSTRACT

We use a method based on metadynamics to locate multiple low-energy Unrestricted Hartree-Fock (UHF) self-consistent-field (SCF) solutions of two model octahedral d1 and d2 transition-metal complexes, [MF6]3- (M = Ti, V). By giving a group-theoretical definition of symmetry breaking, we classify these solutions in the framework of representation theory and observe that a number of them break spin or spatial symmetry, if not both. These solutions seem unphysical at first, but we show that they can be used as bases for Non-Orthogonal Configuration Interaction (NOCI) to yield multideterminantal wave functions that have the right symmetry to be assigned to electronic terms. Furthermore, by examining the natural orbitals and occupation numbers of these NOCI wave functions, we gain insight into the amount of static correlation that they incorporate. We then investigate the behaviors of the most low-lying UHF and NOCI wave functions when the octahedral symmetry of the complexes is lowered and deduce that the symmetry-broken UHF solutions must first have their symmetry restored by NOCI before they can describe any vibronic stabilization effects dictated by the Jahn-Teller theorem.

10.
Open Forum Infect Dis ; 5(5): ofy080, 2018 May.
Article in English | MEDLINE | ID: mdl-29876364

ABSTRACT

BACKGROUND: Transplant recipients presenting with cytomegalovirus (CMV) disease at the time of diagnosis of CMV DNAemia pose a challenge to a preemptive CMV management strategy. However, the rate and risk factors of such failure remain uncertain. METHODS: Solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT) recipients with a first episode of CMV polymerase chain reaction (PCR) DNAemia within the first year posttransplantation were evaluated (n = 335). Patient records were reviewed for presence of CMV disease at the time of CMV DNAemia diagnosis. The distribution and prevalence of CMV disease were estimated, and the odds ratio (OR) of CMV disease was modeled using logistic regression. RESULTS: The prevalence of CMV disease increased for both SOT and HSCT with increasing diagnostic CMV PCR load and with screening intervals >14 days. The only independent risk factor in multivariate analysis was increasing CMV DNAemia load of the diagnostic CMV PCR (OR = 6.16; 95% confidence interval, 2.09-18.11). Among recipients receiving weekly screening (n = 147), 16 (10.8%) had CMV disease at the time of diagnosis of CMV DNAemia (median DNAemia load 628 IU/mL; interquartile range, 432-1274); 93.8% of these cases were HSCT and lung transplant recipients. CONCLUSIONS: Despite application of weekly screening intervals, HSCT and lung transplant recipients in particular presented with CMV disease at the time of diagnosis of CMV DNAemia. Additional research to improve the management of patients at risk of presenting with CMV disease at low levels of CMV DNAemia and despite weekly screening is warranted.

13.
Dis Esophagus ; 30(10): 1-8, 2017 Oct 01.
Article in English | MEDLINE | ID: mdl-28859382

ABSTRACT

Proton pump inhibitors (PPIs) are the most effective treatment for gastroesophageal reflux disease (GERD); however, a considerable number of patients fail to respond to PPI therapy and complain of nocturnal heartburn and sleep disturbance. The aims of this study are to evaluate the treatment pattern of GERD-related medications and their efficacy in relieving nocturnal heartburn. A total of 334 patients with GERD receiving PPI therapy within 6 months were enrolled in a multihospital questionnaire survey from January, 2014 to March, 2015. GERD symptoms and patients' satisfaction were assessed by patient questionnaires, and treatment patterns of GERD-related medications were assessed by investigators. Among the 334 patients, 95.8% used PPI once daily and 58.6% used a half-dose of PPI. The PPI treatment pattern was changed in 26.6% of all patients, of those, 54% of the patients doubled the PPI dose, and 29.2% of the patients switched to another PPI. Approximately 60.3% of all patients were prescribed more than three GERD-related medications. The overall satisfaction rate was 61.8%, and 32.2% of patients experienced nocturnal heartburn and sleep disturbance. In the extended-release PPI group, there were fewer nocturnal symptoms compared with the conventional PPI group (10% vs. 33.7%, respectively, P = 0.027). The use of more than three medications was inversely associated with patients' satisfaction (OR = 0.355, 95% CI; 0.197-0.642, P = 0.001). Most patients were prescribed adjunctive medications other than PPIs; however, patients' satisfaction was inversely associated with multiple drugs. Patients' satisfaction was superior in extended-release PPIs than conventional PPIs for the relief of nocturnal heartburn in Korean patients.


Subject(s)
Gastroesophageal Reflux/drug therapy , Heartburn/drug therapy , Patient Satisfaction/statistics & numerical data , Proton Pump Inhibitors/therapeutic use , Adult , Aged , Aged, 80 and over , Delayed-Action Preparations/therapeutic use , Drug Prescriptions/statistics & numerical data , Drug Substitution/statistics & numerical data , Dyssomnias/etiology , Female , Gastroesophageal Reflux/complications , Heartburn/etiology , Humans , Life Style , Male , Middle Aged , Proton Pump Inhibitors/administration & dosage , Republic of Korea , Surveys and Questionnaires , Symptom Assessment , Young Adult
14.
BMC Cardiovasc Disord ; 17(1): 199, 2017 07 24.
Article in English | MEDLINE | ID: mdl-28738781

ABSTRACT

BACKGROUND: Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA) is common with a prevalence of 6% of all patients fulfilling the diagnosis of myocardial infarction. MINOCA should be considered a working diagnosis. Cardiac Magnetic Resonance (CMR) imaging has recently been suggested to be of great value to determine the cause behind MINOCA. The objectives of this paper are to describe the rationale behind the second Stockholm Myocardial Infarction with Normal Coronaries (SMINC-2) study and to discuss the protocol for investigation of MINOCA patients in the light of the recently published position paper from the European Society of Cardiology. METHODS: The SMINC-2 study is an open non-randomised study using historical controls for comparison. The primary aim is to prove that MINOCA patients investigated with the latest CMR imaging technique can achieve a diagnosis in 70% of all cases entirely by imaging. By including 150 patients we will have >80% chance to prove that the diagnostic accuracy can be improved by 20 absolute % with a p-value of less than 0.05 when compared with CMR imaging in the SMINC-1 study. Furthermore, in addition to invasive coronary angiography, coronary arteries are evaluated by computed tomography angiography to investigate coronary causes and questionnaires are used to describe Quality-of-Life (QoL). By January 1st 2017, 75 patients have been included. DISCUSSION: Whether CMR imaging can provide a diagnosis to an adequate proportion of MINOCA patients is unknown. Well-defined inclusion and exclusion criteria will be used to compare a MINOCA cohort from the population with an appropriate control group. Positive results are likely to influence future guidelines of the management of MINOCA. Furthermore, the study will give mechanistic insights into MINOCA in particular in patients with "true" myocardial infarction and describe QoL in this vulnerable group of patients. TRIAL REGISTRATION: Clinical Trials NCT02318498 .


Subject(s)
Coronary Vessels/diagnostic imaging , Magnetic Resonance Imaging, Cine , Myocardial Infarction/diagnostic imaging , Adult , Aged , Case-Control Studies , Clinical Protocols , Computed Tomography Angiography , Coronary Angiography/methods , Female , Historically Controlled Study , Humans , Male , Middle Aged , Predictive Value of Tests , Quality of Life , Research Design , Surveys and Questionnaires , Sweden
15.
Eur J Nucl Med Mol Imaging ; 44(3): 421-431, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27838763

ABSTRACT

PURPOSE: Solid organ transplant (SOT) recipients are at high risk of developing infections and malignancies. 18F-FDG PET/CT may enable timely detection of these diseases and help to ensure early intervention. We aimed to describe the clinical utility of FDG PET/CT in consecutive, diagnostic unresolved SOT recipients transplanted from January 2004 to May 2015. METHODS: Recipients with a post-transplant FDG PET/CT performed as part of diagnostic work-up were included. Detailed chart reviews were done to extract relevant clinical information and determine the final diagnosis related to the FDG PET/CT. Based on á priori defined criteria and the final diagnosis, results from each scan were classified as true or false, and diagnostic values determined. RESULTS: Among the 1,814 recipients in the cohort, 145 had an FDG PET/CT performed; 122 under the indication of diagnostically unresolved symptoms with a suspicion of malignancy or infection. The remaining (N = 23) had an FDG PET/CT to follow-up on a known disease or to stage a known malignancy. The 122 recipients underwent a total of 133 FDG PET/CT scans performed for a suspected malignancy (66 %) or an infection (34 %). Sensitivity, specificity, and positive and negative predictive values of the FDG PET/CT in diagnosing these conditions were 97, 84, 87, and 96 %, respectively. CONCLUSION: FDG PET/CT is an accurate diagnostic tool for the work-up of diagnostic unresolved SOT recipients suspected of malignancy or infection. The high sensitivity and NPV underlines the potential usefulness of PET/CT for excluding malignancy or focal infections in this often complex clinical situation.


Subject(s)
Fluorodeoxyglucose F18 , Infections/diagnostic imaging , Neoplasms/diagnostic imaging , Organ Transplantation/adverse effects , Positron Emission Tomography Computed Tomography , Postoperative Complications/diagnostic imaging , Radiopharmaceuticals , Adult , Female , Humans , Infections/etiology , Male , Middle Aged , Neoplasms/etiology
16.
Sci Rep ; 6: 37354, 2016 11 22.
Article in English | MEDLINE | ID: mdl-27874027

ABSTRACT

Contractile dysfunction is underdiagnosed in early stages of diabetic cardiomyopathy. We evaluated the potential of circulating long non-coding RNAs (lncRNAs) as biomarkers of subclinical cardiac abnormalities in type 2 diabetes. Forty-eight men with well-controlled type 2 diabetes and 12 healthy age-matched volunteers were enrolled in the study. Left ventricular (LV) parameters were measured by magnetic resonance imaging. A panel of lncRNAs was quantified in serum by RT-qPCR. No differences in expression levels of lncRNAs were observed between type 2 diabetes patients and healthy volunteers. In patients with type 2 diabetes, long intergenic non-coding RNA predicting cardiac remodeling (LIPCAR) was inversely associated with diastolic function, measured as E/A peak flow (P < 0.050 for all linear models). LIPCAR was positively associated with grade I diastolic dysfunction (P < 0.050 for all logistic models). Myocardial infarction-associated transcript (MIAT) and smooth muscle and endothelial cell-enriched migration/differentiation-associated long noncoding RNA (SENCR) were directly associated with LV mass to LV end-diastolic volume ratio, a marker of cardiac remodelling (P < 0.050 for all linear models). These findings were validated in a sample of 30 patients with well-controlled type 2 diabetes. LncRNAs are independent predictors of diastolic function and remodelling in patients with type 2 diabetes.


Subject(s)
Biomarkers/blood , Diabetes Mellitus, Type 2/blood , RNA, Long Noncoding/blood , Ventricular Function, Left , Ventricular Remodeling , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/physiopathology , Heart/diagnostic imaging , Heart/physiopathology , Humans , Magnetic Resonance Imaging , Male , Middle Aged , RNA, Long Noncoding/genetics
17.
Blood Cancer J ; 6(11): e499, 2016 11 11.
Article in English | MEDLINE | ID: mdl-27834937

ABSTRACT

The treatment of chronic lymphocytic leukemia (CLL) is in rapid transition, and during recent decades both combination chemotherapy and immunotherapy have been introduced. To evaluate the effects of this development, we identified all CLL patients registered in the nation-wide Danish Cancer Register between 1978 and 2013. We identified 10 455 CLL patients and 508 995 CLL-free control persons from the general population. Compared with the latter, the relative mortality rate between CLL patients and their controls decreased from 3.4 (95% CI 3.2-3.6) to 1.9 (95% CI 1.7-2.1) for patients diagnosed in 1978-1984 and 2006-2013, respectively. The improved survival corresponded to a decreasing risk of death from malignant hematological diseases, whereas the risk of death from infections was stable during the study period. These population-based data substantiate the improved survival for patients treated with chemo-immunotherapy demonstrated in clinical studies.


Subject(s)
Drug Therapy , Immunotherapy , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/immunology , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Denmark , Disease-Free Survival , Female , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/epidemiology , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Male , Middle Aged
18.
EBioMedicine ; 2(7): 699-705, 2015 Jul.
Article in English | MEDLINE | ID: mdl-26288842

ABSTRACT

BACKGROUND: Cytomegalovirus (CMV) infection in transplant recipients is reported to replicate with a doubling time of 1.2-2 days, and weekly screening is recommended for early diagnosis. We re-evaluated these features in our cohort of transplant recipients. METHODS: The CMV doubling time of the first CMV infection in the first year post-transplant could be calculated for 193 recipients of haematopoietic stem cell or solid organ transplantation. Factors determining the proportion of recipients with a high diagnostic CMV viral load (≥ 18,200 IU/mL) were explored using mathematical simulation. FINDINGS: The overall median doubling time was 4.3 days (IQR 2.5-7.8) and was not influenced by prior CMV immunity, or type of transplantation (p > 0.4). Assuming a fixed doubling time of 1.3 days and screening intervals of 7 or 10 days, 11.1% and 33.3% were projected to have a high CMV viral load at diagnosis, compared to 1.4% and 4.3% if the doubling time varies as observed in our cohort. Consistently, 1.9% of recipients screened weekly had a high diagnostic virus load. INTERPRETATION: Screening intervals can be extended to 10 days in cohorts with comparable CMV doubling time, whereas shorter than 7 days is required in cohorts with shorter doubling times to maintain pre-emptive screening quality.


Subject(s)
Cytomegalovirus Infections/virology , Cytomegalovirus/physiology , Transplantation , Virus Replication , Adult , Cohort Studies , Computer Simulation , Cytomegalovirus Infections/diagnosis , Female , Humans , Kinetics , Male , Middle Aged , Time Factors
19.
Am J Transplant ; 13(2): 458-66, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23282281

ABSTRACT

(Val)ganciclovir is used to treat cytomegalovirus (CMV) infection following solid organ (SOT) or hematopoietic stem cell (HSCT) transplantation. Treatment failures occur, but the contribution from 39 known ganciclovir-related mutations (GRMs) in the CMV-UL97 gene remains controversial. We propose a categorization of these GRMs potentially useful when interpreting sequence analyses in clinical settings. The UL97 gene was sequenced from first/recurrent CMV infections among consecutive SOT or HSCT recipients during 2004-2009. GRMs were categorized as: Signature GRM (sGRM) if in vitro ganciclovir IC(50) ratio for mutated versus wild-type virus >2 (n = 24); polymorphic GRM (pGRM) if ratio <2 (n = 15). (Val)ganciclovir treatment failure was defined as persistent viremia for 30 days or switch to foscarnet within this period. Of 99 (49 HSCT and 50 SOT) recipients with one CMV infection episode, 15 (13 HSCT and 2 SOT) experienced a total of 19 recurrent infection episodes. The prevalence of sGRM was 0% at start of first episode, whereas at start of recurrent episodes, prevalence was 37%. Only one sGRM was present at a time in individual patients. Patients with CMV containing an sGRM (vs. wild type)-but not with a pGRM-were at excess risk of treatment failure (odds ratio = 70.6 [95% CI:8.2-609.6]; p < 0.001). sGRMs emerged only following longer termed use of antiherpetic drugs and usually in recurrent CMV infection episodes. Risk of ganciclovir treatment failure was raised if an sGRM was detected.


Subject(s)
Cytomegalovirus Infections/drug therapy , Cytomegalovirus/drug effects , Drug Resistance, Viral , Ganciclovir/pharmacology , Organ Transplantation/adverse effects , Adult , Cytomegalovirus/genetics , Cytomegalovirus Infections/etiology , Female , Foscarnet/pharmacology , Hematopoietic Stem Cell Transplantation , Humans , Inhibitory Concentration 50 , Male , Middle Aged , Mutation , Odds Ratio , Organ Transplantation/methods , Phosphotransferases (Alcohol Group Acceptor)/genetics , Prevalence , Recurrence , Risk Factors , Time Factors , Treatment Outcome , Young Adult
20.
J Intern Med ; 273(2): 189-96, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22742529

ABSTRACT

OBJECTIVES: Myocardial infarction with angiographically normal coronary arteries (MINCA) is an important subtype of myocardial infarction; however, the prevalence, underlying pathophysiology, prognosis and optimal management of this condition are still largely unknown. Cardiovascular magnetic resonance (CMR) imaging has the potential to clarify the underlying pathology in patients with MINCA. The objective of this study was to investigate the diagnostic value of CMR imaging in this group of patients. DESIGN: The prospective, multicentre, observational Stockholm Myocardial Infarction with Normal Coronaries (SMINC) study. SETTING: Coronary care units in the Stockholm metropolitan area. SUBJECTS: Patients between 35 and 70 years of age with MINCA were consecutively included in the screening phase of the SMINC study. All patients had a typical clinical presentation, fulfilling the universal definition of myocardial infarction and had normal coronary angiography finding. Patients with known structural or coronary heart disease or other known causes of elevated troponin levels were excluded. RESULTS: In total, 176 patients with MINCA were screened from 2007 to 2011. Of these, 152 underwent CMR imaging. The investigation was performed a median of 12 (interquartile range 6-28) days after hospital admission; 67% of the findings were normal, whereas 19% of patients had signs of myocardial necrosis and 7% had signs of myocarditis. The remaining patients (7%) had either unrecognized hypertrophic cardiomyopathy or could not be classified. CONCLUSION: In this consecutive series of patients with MINCA, CMR imaging may help to differentiate between those with myocarditis, myocardial necrosis and normal myocardium. The incidence of MINCA was higher than previously reported. After excluding cases of myocarditis, MINCA consists of a large group of patients with normal CMR imaging results and a smaller group with myocardial necrosis. The aetiologies of these different imaging findings need to be explored.


Subject(s)
Coronary Angiography/methods , Coronary Vessels/diagnostic imaging , Myocardial Infarction/diagnostic imaging , Adult , Aged , Cohort Studies , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Prospective Studies , Severity of Illness Index , Sweden
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