| 109771. |
- Hofer, Anders
(författare)
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How tumors hijack macrophages for immune evasion
- 2024
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Ingår i: Nature Cancer. - : Springer Nature. - 2662-1347. ; 5:8, s. 1134-1135
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Tidskriftsartikel (refereegranskat)abstract
- Resistance of cancers to immune checkpoint blockades is frequently observed. Pancreatic cancer cells are now shown to create a tumor microenvironment that protects them from immunotherapy by overexpression of cytidine deaminase. This leads to increased production of uridine diphosphate that attracts immunosuppressive macrophages.
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| 109772. |
- Hofer, M., et al.
(författare)
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International periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome cohort: description of distinct phenotypes in 301 patients
- 2014
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 53:6, s. 1125-1129
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. The aims of this study were to describe the clinical features of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) and identify distinct phenotypes in a large cohort of patients from different countries. Methods. We established a web-based multicentre cohort through an international collaboration within the periodic fevers working party of the Pediatric Rheumatology European Society (PReS). The inclusion criterion was a diagnosis of PFAPA given by an experienced paediatric rheumatologist participating in an international working group on periodic fever syndromes. Results. Of the 301 patients included from the 15 centres, 271 had pharyngitis, 236 cervical adenitis, 171 oral aphthosis and 132 with all three clinical features. A total of 228 patients presented with additional symptoms (131 gastrointestinal symptoms, 86 arthralgias and/or myalgias, 36 skin rashes, 8 neurological symptoms). Thirty-one patients had disease onset after 5 years and they reported more additional symptoms. A positive family history for recurrent fever or recurrent tonsillitis was found in 81 patients (26.9%). Genetic testing for monogenic periodic fever syndromes was performed on 111 patients, who reported fewer occurrences of oral aphthosis or additional symptoms. Twenty-four patients reported symptoms (oral aphthosis and malaise) outside the flares. The CRP was >50 mg/l in the majority (131/190) of the patients tested during the fever. Conclusion. We describe the largest cohort of PFAPA patients presented so far. We confirm that PFAPA may present with varied clinical manifestations and we show the limitations of the commonly used diagnostic criteria. Based on detailed analysis of this cohort, a consensus definition of PFAPA with better-defined criteria should be proposed.
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| 109773. |
- Hoff, Erik, et al.
(författare)
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Modification of Endotypic Traits in OSA by the Carbonic Anhydrase Inhibitor Sulthiame
- 2024
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Ingår i: CHEST. - 0012-3692 .- 1931-3543. ; 165:3, s. 704-715
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The carbonic anhydrase inhibitor sulthiame reduces OSA severity, increases overnight oxygenation, and improves sleep quality. Insights into how sulthiame modulates OSA pathophysiologic features (endotypic traits) adds to our understanding of the breathing disorder itself, as well as the effects of carbonic anhydrases in respiratory regulation. RESEARCH QUESTION: How does sulthiame treatment modify endotypic traits in OSA? STUDY DESIGN AND METHODS: Per -protocol tertiary analysis of a randomized controlled trial with the inclusion criteria as follow:BMI, >= 20 to # 35 kg/m(2) ; age, 18-75 years; apneahypopnea index (AHI) >= 15 events/h; Epworth sleepiness scale score, >= 6; as well as nonacceptance or nontolerance of positive airway pressure treatment. Patients were randomized to receive placebo (n = 22), sulthiame 200 mg (n = 12), or sulthiame 400 mg (n = 24) during 4 weeks of treatment. Polysomnography was applied twice at baseline and follow-up. Endotypic traits were determined from polysomnography tracings (PUPBeta). Sulthiame plasma concentration was analyzed. Differences from baseline to follow-up ( A s) were analyzed with the analysis of covariance or Kruskal-Wallis H test and Pearson ( r ) or Spearman correlations (r(s)). RESULTS: Sulthiame (200 -mg and 400 -mg groups) consistently reduced loop gain (response to a 1-cycle/min disturbance, Delta G(1) ; mean, - 0.16 [95% CI, - 0.18 to - 0.13]; P < .05) in addition to increased ventilation at lowest decile of ventilatory drive (V (min) ; median, + 12 [95% CI, 420]; P < .05) and median ventilation at eupneic ventilatory drive (V- passive ; median, + 4 [95% CI, 0-5]; P < .05). A Delta G(1 )correlated with A AHI percentage (200 mg: r = 0.65; P < .05). V (min )and V- passive correlated with A AHI (all sulthiame: r(s)= - 0.59 and r(s) = - 0.65; P < .05 for all). The reduction of Delta G(1) was seen already in the lower sulthiame concentration range, whereas changes in V (min) peaked in the higher range. INTERPRETATION: The effect of sulthiame in OSA may be explained by a reduction of ventilatory instability (Delta G(1)) as well as upper airway collapsibility (V (min) and V- passive ).
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| 109774. |
- Hoff, Erik
(författare)
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Pharmacological therapy in obstructive sleep apnea - Methodology and interventional aspects of carbonic anhydrase modulation
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND: Obstructive sleep apnea (OSA) is a highly prevalent disease with potential severe short- and long-term consequences such as daytime sleepiness and cardiovascular disease. Recurrent total or partial collapse of the upper airway during sleep leads to sleep fragmentation and intermittent hypoxia/hypercapnia. The underlying mechanisms include a collapsible upper airway, unstable ventilation, low arousal threshold and insufficient muscle compensation in the pharynx region. The main treatments, positive airway pressure (PAP) and mandibular advancement devices, mainly address anatomical causes of OSA. In many patients, these treatments are not tolerated or not efficient enough. Improved understanding of pathophysiological mechanisms in OSA have paved the way for new treatment targets. In this thesis, carbonic anhydrase (CA) activity as a biomarker for OSA is investigated together with studies on CA inhibition as a therapy in OSA, in addition to a systematic evaluation of placebo effects in drug treatments of OSA. METHODS AND RESULTS: In paper I, we studied a cohort of 33 PAP-treated subjects with OSA and 9 OSA patients treated with PAP, the CA inhibitor acetazolamide (ACT) and a combination of PAP+ACT. We could show that CA activity in whole blood was higher in hypertensive compared to normotensive participants and PAP treatment per se did not reduce CA activity. Further, CA activity was numerically reduced by ACT. Paper II contained a detailed analysis of 58 patients participating in a randomised controlled trial of the CA inhibitor sulthiame (STM) in moderate to severe OSA. By using a PSG-based analysis method, we investigated the effects of STM on underlying pathomechanisms of OSA. STM reduced ventilatory instability and increased the upper airway stability. In paper III, the effect of STM on potential biochemical markers of OSA was investigated. CA activity in whole blood was reduced by STM and this effect remained two weeks after the last drug intake. Hypoxia-inducible factor 1α, a key factor in the cellular response to hypoxia, was reduced during treatment and at two weeks after last drug intake, suggesting an overall improvement of overnight O2 saturation following STM. In paper IV we analysed the placebo effect of drug treatments in OSA by means of a systematic review with meta-analyses. Objective measures of OSA were not systematically affected by placebo whereas placebo effects in subjective symptoms like excessive daytime sleepiness need to be accounted for. CONCLUSIONS: The CA system plays an important part in OSA pathophysiology and appears to be a promising treatment target. Further studies are needed to evaluate CA activity in whole blood as a diagnostic biomarker in OSA. The CA inhibitor STM had dual effects in OSA including a reduction of ventilatory instability and an increase in upper airway stability. Future studies in pharmacological treatment of OSA need to be significantly sized and placebo controlled for subjective outcomes.
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| 109775. |
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| 109776. |
- Hoff, Lena, et al.
(författare)
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In the shadow of bad news - views of patients with acute leukaemia, myeloma or lung cancer about information, from diagnosis to cure or death
- 2007
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Ingår i: BMC Palliative Care. - 1472-684X. ; 6:Article nr. 1
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Tidskriftsartikel (refereegranskat)abstract
- Many studies have been published about giving and receiving bad messages. However, only a few of them have followed the patients all the way through a disease as is done in this study. Many studies have been written about patients' coping strategies. In this study we will keep within the bounds of coping through information only. The aim of the study is to investigate patients' views of information during the trajectory of their disease, whether their reactions differ from each other and whether they differ in different phases of the disease.
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| 109777. |
- Hoff, Leonardo Santos, et al.
(författare)
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COVID-19 severity and vaccine breakthrough infections in idiopathic inflammatory myopathies, other systemic autoimmune and inflammatory diseases, and healthy controls : a multicenter cross-sectional study from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) survey
- 2023
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Ingår i: Rheumatology International. - : Springer. - 0172-8172 .- 1437-160X. ; 43:1, s. 47-58
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: We aimed to compare the spectrum and severity of COVID-19 and vaccine breakthrough infections (BIs) among patients with IIMs, other systemic autoimmune and inflammatory diseases (SAIDs), and healthy controls (HCs).METHODS: This is a cross-sectional study with data from the COVAD study, a self-reported online global survey that collected demographics, COVID-19 history, and vaccination details from April to September 2021. Adult patients with at least one COVID-19 vaccine dose were included. BIs were defined as infections occurring > 2 weeks after any dose of vaccine. Characteristics associated with BI were analyzed with a multivariate regression analysis.RESULTS: Among 10,900 respondents [42 (30-55) years, 74%-females, 45%-Caucasians] HCs were (47%), SAIDs (42%) and IIMs (11%). Patients with IIMs reported fewer COVID-19 cases before vaccination (6.2%-IIM vs 10.5%-SAIDs vs 14.6%-HC; OR = 0.6, 95% CI 0.4-0.8, and OR = 0.3, 95% CI 0.2-0.5, respectively). BIs were uncommon (1.4%-IIM; 1.9%-SAIDs; 3.2%-HC) and occurred in 17 IIM patients, 13 of whom were on immunosuppressants, and 3(18%) required hospitalization. All-cause hospitalization was higher in patients with IIM compared to HCs [23 (30%) vs 59 (8%), OR = 2.5, 95% CI 1.2-5.1 before vaccination, and 3 (18%) vs 9 (5%), OR = 2.6, 95% CI 1.3-5.3 in BI]. In a multivariate regression analysis, age 30-60 years was associated with a lower odds of BI (OR = 0.7, 95% CI 0.5-1.0), while the use of immunosuppressants had a higher odds of BI (OR = 1.6, 95% CI 1.1-2.7).CONCLUSIONS: Patients with IIMs reported fewer COVID-19 cases than HCs and other SAIDs, but had higher odds of all-cause hospitalization from COVID-19 than HCs. BIs were associated with the use of immunosuppressants and were uncommon in IIMs.
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| 109778. |
- Hoff, Maria, 1981, et al.
(författare)
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Accuracy of automated pure-tone audiometry in population-based samples of older adults
- 2023
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Ingår i: International Journal of Audiology. - 1499-2027.
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveAutomated pure-tone audiometry is frequently used in teleaudiology and hearing screening. Given the high prevalence of age-related hearing loss, older adults are an important target population. This study aimed to investigate the accuracy of automated audiometry in older adults, and to examine the influence of test frequency, age, sex, hearing and cognitive status.Design and study sampleIn a population-based study, two age-homogeneous samples of 70-year-olds (n = 238) and 85-year-olds (n = 114) were tested with automated audiometry in an office using circum-aural headphones and, around 4 weeks later, with manual audiometry conducted to clinical standards. The differences were analysed for individual frequencies (range: 0.25-8 kHz) and pure-tone averages.ResultsThe mean difference varied across test frequencies and age groups, the overall figure being -0.7 dB (SD = 8.8, p < 0.001), and 68% to 94% of automated thresholds corresponded within +/- 10 dB of manual thresholds. The poorest accuracy was found at 8 kHz. Age, sex, hearing and cognitive status were not associated with the accuracy (ordinal regression analysis).ConclusionsAutomated audiometry seems to produce accurate assessments of hearing sensitivity in the majority of older adults, but with larger error margins than in younger populations, and is not affected by relevant patient factors associated with old age.
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| 109779. |
- Hoff, Maria, 1981, et al.
(författare)
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Auditory function and prevalence of specific ear and hearing related pathologies in the general population at age 70.
- 2020
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Ingår i: International journal of audiology. - : Informa UK Limited. - 1708-8186 .- 1499-2027. ; 59:9, s. 682-693
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To describe the auditory function in early old age in detail based on both psychoacoustic and physiological measures, and to investigate the prevalence of specific audiological and otological pathologies.Design: An unscreened subsample from a population-based geriatric investigation was examined with otoscopy; tympanometry; pure-tone audiometry; word-recognition-in-noise test; distortion-product otoacoustic emissions; and auditory-evoked brainstem responses. Audiometric subtypes and diagnoses were established based on set criteria. The association between word scores and ABR was examined with linear regression analysis.Study Sample: 251 persons aged 70 (113 men, 138 women, born in 1944) that were representative of the inhabitants of the city of Gothenburg.Results: The prevalence of conductive pathology was 2% versus 49% for cochlear and 2% for auditory-neural pathology. Four percent had indeterminate type. Cochlear dysfunction was present in the majority of ears and around 20% performed worse-than-expected on speech testing. Poor performance on the speech in noise test was associated with prolonged interpeak latency interval of ABR waves I-V.Conclusion: Specific otological and audiological pathologies, other than cochlear hearing loss, are rare in the general population at age 70. Additionally, there is subtle evidence of age-related decline of the auditory nerve. Longitudinal follow-up would be of great interest.
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| 109780. |
- Hoff, Maria, 1981
(författare)
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Hearing in early old age: current perspectives
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Age related hearing loss is a public health concern that restricts the possibilities of older persons to lead a healthy, social and active life. The present thesis aims to provide contemporary perspectives on age related hearing function and hearing loss in the general population, in early old age. The thesis is based on data from the Gothenburg H70 Birth Cohort Study, a prospective epidemiological investigation of ageing, in which representative segments of the older population are examined with a wide-ranging test protocol covering multiple aspects of health. The four papers, on which the thesis is built, examine various hearing parameters in a recent birth cohort of 70-year-olds, born in 1944. The results from Paper I demonstrated that the prevalence of hearing loss has decreased significantly among 70-year-olds in Gothenburg, across a time period of nearly five decades (1971-2014). Reductions in exposure to occupational noise is probably one of the most important factors explaining the findings. In Paper II, auditory function was investigated in detail based on a comprehensive audiological test battery performed in a subsample. The results demonstrated that cochlear pathology is the predominant cause of hearing loss at age 70, but that early neural ageing is present, leading to poorer speech recognition in some individuals. In Paper III, a comparison was made between automated and conventional pure-tone audiometry in 70-year olds and 85-year olds (born in 1930). The results indicated that automated pure-tone audiometry is a valid test method in the majority of older persons, and that age, hearing loss and cognitive status did not affect the outcomes. Finally, in Paper IV it was demonstrated that poorer hearing is associated with poorer cognitive function, but only when considering pure-tone and speech measures, and not self-report. Hearing aid use was associated with better cognitive scores. In conclusion, hearing loss - of various underlying pathology - is a prevalent condition in early old age that is associated with poorer cognition. Given the rapid ageing of populations in Sweden, and worldwide, efforts of prevention, early identification and rehabilitation of age related hearing loss should be considered a public health priority.
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