| 41. |
- Sundvall, Pär-Daniel, et al.
(författare)
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Evaluation of dipstick analysis among elderly residents to detect bacteriuria: a cross-sectional study in 32 nursing homes.
- 2009
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Ingår i: BMC geriatrics. - : Springer Science and Business Media LLC. - 1471-2318. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Few studies have evaluated dipstick urinalysis for elderly and practically none present confidence intervals. Furthermore, most previous studies combine all bacteria species in a "positive culture". Thus, their evaluation may be inappropriate due to Yule-Simpson's paradox. The aim of this study was to evaluate diagnostic accuracy of dipstick urinalysis for the elderly in nursing homes. METHODS: In this cross-sectional study voided urine specimens were collected from 651 elderly individuals in nursing homes. Dipstick urinalysis for nitrite, leukocyte esterase and urine culture were performed. Sensitivity, specificity, positive and negative predictive values with 95% confidence intervals were calculated. Visual readings were compared to readings with a urine chemistry analyzer. RESULTS: 207/651 (32%) of urine cultures showed growth of a potentially pathogenic bacterium. Combining the two dipsticks improved test characteristics slightly compared to using only one of the dipsticks. When both dipsticks are negative, presence of potentially pathogenic bacteria can be ruled out with a negative predictive value of 88 (84-92)%. Visual and analyzer readings had acceptable agreement. CONCLUSION: When investigating for bacteriuria in elderly people at nursing homes we suggest nitrite and leukocyte esterase dipstick be combined. There are no clinically relevant differences between visual and analyzer dipstick readings. When dipstick urinalysis for nitrite and leukocyte esterase are both negative it is unlikely that the urine culture will show growth of potentially pathogenic bacteria and in a patient with an uncomplicated illness further testing is unnecessary.
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| 42. |
- Sundvall, Pär-Daniel, et al.
(författare)
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Interleukin-6 concentrations in the urine and dipstick analyses were related to bacteriuria but not symptoms in the elderly: a cross sectional study of 421 nursing home residents
- 2014
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Ingår i: BMC Geriatrics. - : Springer Science and Business Media LLC. - 1471-2318. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Up to half the residents of nursing homes for the elderly have asymptomatic bacteriuria (ABU), which should not be treated with antibiotics. A complementary test to discriminate between symptomatic urinary tract infections (UTI) and ABU is needed, as diagnostic uncertainty is likely to generate significant antibiotic overtreatment. Previous studies indicate that Interleukin-6 (IL-6) in the urine might be suitable as such a test. The aim of this study was to investigate the association between laboratory findings of bacteriuria, IL-6 in the urine, dipstick urinalysis and newly onset symptoms among residents of nursing homes. Methods: In this cross sectional study, voided urine specimens for culture, urine dipstick and IL-6 analyses were collected from all residents capable of providing a voided urine sample, regardless of the presence of symptoms. Urine specimens and symptom forms were provided from 421 residents of 22 nursing homes. The following new or increased nonspecific symptoms occurring during the previous month were registered; fatigue, restlessness, confusion, aggressiveness, loss of appetite, frequent falls and not being herself/himself, as well as symptoms from the urinary tract; dysuria, urinary urgency and frequency. Results: Recent onset of nonspecific symptoms was common among elderly residents of nursing homes (85/421). Urine cultures were positive in 32% (135/421), Escherichia coli was by far the most common bacterial finding. Residents without nonspecific symptoms had positive urine cultures as often as those with nonspecific symptoms with a duration of up to one month. Residents with positive urine cultures had higher concentrations of IL-6 in the urine (p < 0.001). However, among residents with positive urine cultures there were no differences in IL-6 concentrations or dipstick findings between those with or without nonspecific symptoms. Conclusions: Nonspecific symptoms among elderly residents of nursing homes are unlikely to be caused by bacteria in the urine. This study could not establish any clinical value of using dipstick urinalysis or IL-6 in the urine to verify if bacteriuria was linked to nonspecific symptoms.
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| 43. |
- Marcisauskas, Simonas, 1988, et al.
(författare)
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Univariate and classification analysis reveals potential diagnostic biomarkers for early stage ovarian cancer Type 1 and Type 2
- 2019
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Ingår i: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; 196, s. 57-68
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Tidskriftsartikel (refereegranskat)abstract
- Biomarkers for early detection of ovarian tumors are urgently needed. Tumors of the ovary grow within cysts and most are benign. Surgical sampling is the only way to ensure accurate diagnosis, but often leads to morbidity and loss of female hormones. The present study explored the deep proteome in well-defined sets of ovarian tumors, FIGO stage I, Type 1 (low-grade serous, mucinous, endometrioid; n = 9), Type 2 (high-grade serous; n = 9), and benign serous (n = 9) using TMT–LC–MS/MS. Data are available via ProteomeXchange with identifier PXD010939. We evaluated new bioinformatics tools in the discovery phase. This innovative selection process involved different normalizations, a combination of univariate statistics, and logistic model tree and naive Bayes tree classifiers. We identified 142 proteins by this combined approach. One biomarker panel and nine individual proteins were verified in cyst fluid and serum: transaldolase-1, fructose-bisphosphate aldolase A (ALDOA), transketolase, ceruloplasmin, mesothelin, clusterin, tenascin-XB, laminin subunit gamma-1, and mucin-16. Six of the proteins were found significant (p <.05) in cyst fluid while ALDOA was the only protein significant in serum. The biomarker panel achieved ROC AUC 0.96 and 0.57 respectively. We conclude that classification algorithms complement traditional statistical methods by selecting combinations that may be missed by standard univariate tests. Significance: In the discovery phase, we performed deep proteome analyses of well-defined histology subgroups of ovarian tumor cyst fluids, highly specified for stage and type (histology and grade). We present an original approach to selecting candidate biomarkers combining several normalization strategies, univariate statistics, and machine learning algorithms. The results from validation of selected proteins strengthen our prior proteomic and genomic data suggesting that cyst fluids are better than sera in early stage ovarian cancer diagnostics.
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| 44. |
- Qvarfordt, Mikaela, Doktorand, 1979-
(författare)
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Environmental exposures, body composition and pulmonary function : How can we improve diagnostics?
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Pulmonary diseases are influenced by numerous factors such as lifestyle, environment, genetics, and adipose tissue. A common factor for these diseases is that early and accurate diagnosis is beneficial for effective treatment. The improvement and development of diagnostic tools, including nanotechnology, offers the potential for more reliable diagnosis.The main aim of this thesis was to improve our understanding of respiratory assessment through a comprehensive approach. This approach included studying the effectiveness of training and feedback in conducting spirometry tests to accepted diagnostic standard (paper I). Evaluating the association of body impedance analysis (BIA) and waist circumference in assessing the decline in lung function induced by excessive adipose tissue (paper II) and investigating the effects of weight change on lung function (paper III). In addition, the thesis investigated the potential of inhaled nano particles in individuals with impaired lung epithelium as a possible new diagnostic method (paper IV). Overall, these studies aimed to improve lung function diagnostics to make them more reliable, accessible and to advance the development of cutting-edge technological methods.Our results show that the use of structured on-line feedback improve the quality of spirometry and that there is a potential gender differences in the effects of excess adipose tissue on lung function. Data also demonstrated a difference in clearance of inhaled nanoparticles between healthy and patients with impaired alveolar integrity, opening the possibility for new diagnostic approaches.
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| 45. |
- Alaridah, Nader, et al.
(författare)
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Transmission dynamics study of tuberculosis isolates with whole genome sequencing in southern Sweden
- 2019
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Epidemiological contact tracing complemented with genotyping of clinical Mycobacterium tuberculosis isolates is important for understanding disease transmission. In Sweden, tuberculosis (TB) is mostly reported in migrant and homeless where epidemiologic contact tracing could pose a problem. This study compared epidemiologic linking with genotyping in a low burden country. Mycobacterium tuberculosis isolates (n = 93) collected at Scania University Hospital in Southern Sweden were analysed with the standard genotyping method mycobacterial interspersed repetitive units-variable number tandem repeats (MIRU-VNTR) and the results were compared with whole genome sequencing (WGS). Using a maximum of twelve single nucleotide polymorphisms (SNPs) as the upper threshold of genomic relatedness noted among hosts, we identified 18 clusters with WGS comprising 52 patients with overall pairwise genetic maximum distances ranging from zero to nine SNPs. MIRU-VNTR and WGS clustered the same isolates, although the distribution differed depending on MIRU-VNTR limitations. Both genotyping techniques identified clusters where epidemiologic linking was insufficient, although WGS had higher correlation with epidemiologic data. To summarize, WGS provided better resolution of transmission than MIRU-VNTR in a setting with low TB incidence. WGS predicted epidemiologic links better which could consolidate and correct the epidemiologically linked cases, avoiding thus false clustering.
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| 46. |
- Berglund, Eva Caroline, et al.
(författare)
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A Study Protocol for Validation and Implementation of Whole-Genome and -Transcriptome Sequencing as a Comprehensive Precision Diagnostic Test in Acute Leukemias
- 2022
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Ingår i: Frontiers in Medicine. - Lausanne, Switzerland : Frontiers Media SA. - 2296-858X. ; 9, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Whole-genome sequencing (WGS) and whole-transcriptome sequencing (WTS), with the ability to provide comprehensive genomic information, have become the focal point of research interest as novel techniques that can support precision diagnostics in routine clinical care of patients with various cancer types, including hematological malignancies. This national multi-center study, led by Genomic Medicine Sweden, aims to evaluate whether combined application of WGS and WTS (WGTS) is technically feasible and can be implemented as an efficient diagnostic tool in patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). In addition to clinical impact assessment, a health-economic evaluation of such strategy will be performed. Methods and Analysis: The study comprises four phases (i.e., retrospective, prospective, real-time validation, and follow-up) including approximately 700 adult and pediatric Swedish AML and ALL patients. Results of WGS for tumor (90×) and normal/germline (30×) samples as well as WTS for tumors only will be compared to current standard of care diagnostics. Primary study endpoints are diagnostic efficiency and improved diagnostic yield. Secondary endpoints are technical and clinical feasibility for routine implementation, clinical utility, and health-economic impact. Discussion: Data from this national multi-center study will be used to evaluate clinical performance of the integrated WGTS diagnostic workflow compared with standard of care. The study will also elucidate clinical and health-economic impacts of a combined WGTS strategy when implemented in routine clinical care. Clinical Trial Registration: [https://doi.org/10.1186/ISRCTN66987142], identifier [ISRCTN66987142].
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| 47. |
- Handlin, Linda, 1981-, et al.
(författare)
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Promoting health of Swedish workers by complementary methods : example of a study design of a longitudinal randomized controlled intervention study
- 2017
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Ingår i: Medical Research Archives. - USA : KEI Journals. - 2375-1916 .- 2375-1924. ; 5:8, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Background: When designing, implementing, and evaluating a work site health promotion program, it is necessary to ensure that the program is evidence based. The present article aims to present in-depth information on the design of a longitudinal randomized controlled complementary intervention pilot study that follows the Consort recommendations to evaluate possible effects of a health promotive intervention in healthy workers.Methods: Employees from four different workplaces were randomly assigned to one of the following groups: i) Massage and mental training (sitting in the armchair and receiving mechanical massage while listening to mental training programs, n=19), ii) Massage (sitting in the armchair and receiving mechanical massage only, n=19), iii) Mental training (sitting in the armchair and listening to mental training programs only, n=19), iv) Pause (sitting in the armchair but not receiving mechanical massage or listening to mental training programs, n=19), v) Control (not sitting in the armchair at all, n=17). The study lasted for eight weeks. Immediately before the randomization, after four weeks and after eight weeks the participants responded to statements from the Swedish Scale of Personality and had their heart rate, blood pressure and fingertip temperature measured.Results: Receiving mechanical massage and listening to mental training programs, either separately or in combination, during working hours had some positive effects on the employees’ own evaluation of their health, as well as their heart rate, blood pressure and fingertip temperature. However, the intervention need to be evaluated further.Conclusion: The approach described makes it possible to design, implement and evaluate a work site health promotion program, also on pilot-study level and these results should be seen as a first step towards larger randomized studies. This types of studies need to focus on healthy participants and special care should be taken to guarantee adequately powered study groups and their homogeneity.
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| 48. |
- Cedervall, Jessica, et al.
(författare)
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Pharmacological targeting of peptidylarginine deiminase 4 prevents cancer-associated kidney injury in mice.
- 2017
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Ingår i: Oncoimmunology. - : Taylor & Francis. - 2162-4011 .- 2162-402X. ; 6:8
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Tidskriftsartikel (refereegranskat)abstract
- Renal insufficiency is a frequent cancer-associated problem affecting more than half of all cancer patients at the time of diagnosis. To minimize nephrotoxic effects the dosage of anticancer drugs are reduced in these patients, leading to sub-optimal treatment efficacy. Despite the severity of this cancer-associated pathology, the molecular mechanisms, as well as therapeutic options, are still largely lacking. We here show that formation of intravascular tumor-induced neutrophil extracellular traps (NETs) is a cause of kidney injury in tumor-bearing mice. Analysis of clinical biomarkers for kidney function revealed impaired creatinine clearance and elevated total protein levels in urine from tumor-bearing mice. Electron microscopy analysis of the kidneys from mice with cancer showed reversible pathological signs such as mesangial hypercellularity, while permanent damage such as fibrosis or necrosis was not observed. Removal of NETs by treatment with DNase I, or pharmacological inhibition of the enzyme peptidylarginine deiminase 4 (PAD4), was sufficient to restore renal function in mice with cancer. Tumor-induced systemic inflammation and impaired perfusion of peripheral vessels could be reverted by the PAD4 inhibitor. In conclusion, the current study identifies NETosis as a previously unknown cause of cancer-associated renal dysfunction and describes a novel promising approach to prevent renal failure in individuals with cancer.
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| 49. |
- Wahlin, Björn Engelbrekt, et al.
(författare)
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T Cells in Tumors and Blood Predict Outcome in Follicular Lymphoma Treated with Rituximab
- 2011
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Ingår i: Clinical Cancer Research. - : American Association for Cancer Research. - 1078-0432 .- 1557-3265. ; 17:12, s. 4136-4144
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: T cells influence outcome in follicular lymphoma, but their contributions seem to be modified by therapy. Their impact in patients receiving rituximab without chemotherapy is unknown. EXPERIMENTAL DESIGN: Using flow cytometry, we evaluated the T cells in tumors and/or blood in a total of 250 follicular lymphoma patients included in two Nordic Lymphoma Group randomized trials that compared single rituximab with IFN-α2a-rituximab combinations. RESULTS: In univariate analysis, higher levels of CD3(+), CD4(+), and CD8(+) T cells in both tumors and blood correlated with superior treatment responses, and in multivariate analysis, tumor-CD3(+) (P = 0.011) and blood-CD4(+) (P = 0.029) cells were independent. CD4(+) cells were favorable regardless of treatment arm, but CD8(+) cells were favorable only in patients treated with single rituximab, because IFN-α2a improved responses especially in patients with low CD8(+) cell levels. Higher levels of blood-CD3(+) (P = 0.003) and blood-CD4(+) (P = 0.046) cells predicted longer overall survival, and higher levels of blood-CD8(+) cells longer times to next treatment (P = 0.046). CONCLUSIONS: We conclude that therapeutic effects of rituximab are augmented by tumor-associated T cells for rapid responses and by systemic T cells for sustained responses. CD4(+) and CD8(+) cells are both favorable in patients treated with rituximab. IFN-α2a abrogates the negative impact of few CD8(+) cells.
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| 50. |
- Cui, Yanhua, et al.
(författare)
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Prior exposure to alkylating agents negatively impacts testicular organoid formation in cells obtained from childhood cancer patients
- 2024
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Ingår i: Human Reproduction Open. - : Oxford University Press. - 2399-3529. ; 2024:3
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Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTIONCan human pre- and peri-pubertal testicular cells obtained from childhood cancer patients, previously treated with chemotherapy, form testicular organoids (TOs)?SUMMARY ANSWEROrganoid formation from testicular tissue collected from childhood cancer patients positively correlates with SRY-Box transcription factor 9 (SOX9) expression in Sertoli cells, which in turn negatively correlates with previous exposure to alkylating chemotherapy.WHAT IS KNOWN ALREADYPre- and peri-pubertal boys exposed to highly gonadotoxic therapies can only safeguard their fertility potential through testicular tissue cryopreservation. Today, there is no established clinical tool to restore fertility using these testicular samples. Organoids hold promise in providing fundamental early insights in creating such platforms. However, the generation of TOs that closely resemble the innate testis, to enable a thorough monitoring of the necessary steps for germ cell differentiation and somatic functionalities, remains a challenge.STUDY DESIGN, SIZE, DURATIONWe used a Matrigel-based three-layer gradient culture system to generate human TOs and to reveal whether chemotherapy exposure affects TO formation capacity and the functionality of pre- and peri-pubertal testicular somatic cells. Testicular cells of 11 boys (aged 7.7 ± 4.1 (mean ± SD) years) were assessed for TO formation in relation to previous chemotherapy exposure and SOX9 expression in histological sections of paraffin-embedded testicular tissue samples collected on the day of biopsy and compared with testicular tissue samples obtained from 28 consecutive patients (aged 6.9 ± 3.8 (mean ± SD) years). All 39 patients were part of the fertility preservation project NORDFERTIL; an additional 10 samples (from boys aged 5.5 ± 3.5 (mean ± SD) years, without an underlying pathology) in an internal biobank collection were used as controls.PARTICIPANTS/MATERIALS, SETTING, METHODSWe obtained 49 testicular tissue samples from boys aged 0.8–13.4 years. Fresh samples (n = 11) were dissociated into single-cell suspensions and applied to a three-layer gradient culture system for organoid formation. Histological sections of another 28 samples obtained as part of the fertility preservation project NORDFERTIL, and 10 samples from a sample collection of a pathology biobank were used to evaluate the effects of prior exposure to alkylating agents on testicular samples. Testicular organoid formation was defined based on morphological features, such as compartmentalized structures showing cord formation, and protein expression of testicular cell-specific markers for germ and somatic cells was evaluated via immunohistochemical staining. Hormone secretion was analysed by specific enzyme-linked immunosorbent assays for testosterone and anti-Müllerian hormone (AMH) production.MAIN RESULTS AND THE ROLE OF CHANCEOur results revealed that 4 out of 11 prepubertal testicular samples formed TOs that showed compartmentalized cord-like structures surrounded by interstitial-like areas and increasing levels of both testosterone as well as AMH over a 7-day culture period. We observed that SOX9 expression was correlated positively with TO formation. Moreover, exposure to alkylating agents before biopsy was inversely correlated with SOX9 expression (P = 0.006).LARGE SCALE DATAN/A.LIMITATIONS, REASONS FOR CAUTIONDue to the limited amount of material available, only 11 out of the 39 pre- and peri-pubertal testicular tissue samples could be used for the organoid formation experiments. The testicular tissue samples obtained from a sample collection of the internal biobank of Department of Pathology, Karolinska University Hospital were considered normal and included in the study if no testicular pathology was reported. However, detailed information regarding previous medical treatments and/or testicular volumes of the patients included in this biobank was not available.WIDER IMPLICATIONS OF THE FINDINGSOur observations suggest that SOX9 expression may serve as a putative indicator of TO formation, indicating a critical role of Sertoli cells in promoting organoid formation, seminiferous tubule integrity, and testicular function in pre- and peri-pubertal testicular tissue.
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