Low incidence of late-onset giant cell arteritis during the first year in patients with polymyalgia rheumatica-a repeated imaging study.

OBJECTIVE: The objective was to investigate the incidence of late-onset giant cell arteritis (GCA) within the first year in patients diagnosed with polymyalgia rheumatica (PMR). METHODS: In this prospective study, treatment-naïve individuals with a new clinical diagnosis of PMR and without GCA symptoms underwent baseline assessments, including vascular ultrasonography and 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography computed tomography (FDG-PET/CT). To prevent biased inclusion, rapid referral clinics were established for all patients suspected of PMR. Additionally, the patients underwent GCA monitoring during clinical visits at weeks 8 and 10, which involved vascular ultrasonography and FDG-PET/CT scans. After one year, a follow-up visit was performed to confirm the PMR diagnosis and perform vascular ultrasonography. RESULTS: A final PMR diagnosis was assigned to 62 patients, excluding 2 patients with concurrent subclinical GCA and PMR at baseline, corresponding to a baseline prevalence of subclinical GCA of 3%. During the one-year follow-up, two PMR patients developed late-onset GCA corresponding to an incidence rate of 32 per 1000 person-years. One patient developed GCA 14 weeks after the PMR diagnosis, exhibiting cranial symptoms and positive vascular ultrasonography. The other patient presented with subclinical large vessel GCA at the one-year visit detected with vascular ultrasonography and confirmed by FDG-PET/CT. CONCLUSION: This study is the first to demonstrate a low incidence rate of late-onset GCA in PMR patients within the first year, employing repeated imaging to exclude GCA at baseline and diagnose GCA during follow-up. Additionally, it provides evidence of a low prevalence of subclinical GCA across the entire PMR population. TRIAL REGISTRATION: ClinicalTrials.Gov, NCT04519580.

Improved Diagnostic Accuracy for Polymyalgia Rheumatica using FDG-PET/CT with Clinical Diagnosis or 2012 ACR/EULAR Classification Criteria.

PURPOSE: In routine care, clinicians may employ 2-[18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) computed tomography (CT) to validate their initial clinical diagnosis of polymyalgia rheumatica (PMR). Nevertheless, the diagnostic utility of combining FDG-PET/CT findings with clinical presentation has not been explored. Therefore, this study aimed to investigate whether the diagnostic accuracy for PMR could be enhanced by combining FDG-PET/CT findings with the clinical baseline diagnosis or the 2012 ACR/EULAR clinical classification criteria for PMR. METHODS: An investigation and a validation cohort were included from two countries, encompassing 66/27 and 36/21 PMR/non-PMR patients, respectively. The cohorts comprised treatment-naïve patients suspected of PMR, who initially received a clinical baseline diagnosis and underwent FDG-PET/CT scans. The FDG-PET/CT Leuven-score was applied to classify patients as either PMR or non-PMR and combined with the clinical baseline diagnosis. Final diagnoses were established through clinical follow-up after twelve or six months in the investigation and validation cohorts, respectively. RESULTS: In the investigation cohort, a clinical baseline diagnosis yielded a sensitivity/specificity of 94%/82%, compared with 78%/70% using the ACR/EULAR criteria. Combining the clinical baseline diagnosis with a positive Leuven-score showed a sensitivity/specificity of 80%/93%, compared with 80%/82% for an ACR/EULAR-Leuven-score. In the validation cohort, the baseline diagnosis revealed a sensitivity/specificity of 100%/91%, compared with 92%/76% using the ACR/EULAR criteria. Combining FDG-PET/CT with the baseline diagnosis demonstrated a sensitivity/specificity of 83%/95% compared with 89%/81% for the ACR/EULAR-Leuven-score. CONCLUSION: Combining FDG-PET/CT findings with the clinical baseline diagnosis or ACR/EULAR clinical classification criteria can improve the diagnostic specificity for PMR.

The effect of prednisolone and a short-term prednisolone discontinuation for the diagnostic accuracy of FDG-PET/CT in polymyalgia rheumatica-a prospective study of 101 patients.

PURPOSE: 2-[18F]Fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) has been suggested as an imaging modality to diagnose polymyalgia rheumatica (PMR). However, the applicability of FDG-PET/CT remains unclear, especially following glucocorticoid administration. This study aimed to investigate the diagnostic accuracy of FDG-PET/CT before and during prednisolone treatment, as well as following short-term prednisolone discontinuation. METHODS: Treatment naïve suspected PMR patients were clinically diagnosed at baseline and subsequently had an FDG-PET/CT performed. Patients diagnosed with PMR were administered prednisolone following the first FDG-PET/CT and had a second FDG-PET/CT performed after 8 weeks of treatment. Subsequently, prednisolone was tapered with short-term discontinuation at week 9 followed by a third FDG-PET/CT at week 10. An FDG-PET/CT classification of PMR/non-PMR was applied, utilizing both the validated Leuven score and a dichotomous PMR score. The final diagnosis was based on clinical follow-up after 1 year. RESULTS: A total of 68 and 27 patients received a final clinical diagnosis of PMR or non-PMR. A baseline FDG-PET/CT classified the patients as having PMR with a sensitivity/specificity of 86%/63% (Leuven score) and 82%/70% (dichotomous score). Comparing the subgroup of non-PMR with inflammatory diseases to the PMR group demonstrated a specificity of 39%/54% (Leuven/dichotomous score). After 8 weeks of prednisolone treatment, the sensitivity of FDG-PET/CT decreased to 36%/41% (Leuven/dichotomous score), while a short-term prednisolone discontinuation increased the sensitivity to 66%/60%. CONCLUSION: FDG-PET/CT has limited diagnostic accuracy for differentiating PMR from other inflammatory diseases. If FDG-PET/CT is intended for diagnostic purposes, prednisolone should be discontinued to enhance diagnostic accuracy. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04519580). Registered 17th of August 2020.

Impact of the COVID-19 pandemic on treat-to-target strategies and physical consultations in >7000 patients with inflammatory arthritis.

OBJECTIVES: To explore the impact of the COVID-19 pandemic on treat-to-target strategies (disease activity, remission rates) and access to physical consultations in patients with inflammatory rheumatic disease, as well as to explore characteristics of patients with/without physical consultations in the clinic and the impact of early vs established disease. METHODS: Patients with RA, PsA or axial SpA (axSpA) prospectively followed in the nationwide DANBIO registry answered online questionnaires and reported patient-reported outcomes (PROs) in June and November 2020. Patient characteristics, disease activity and physical consultations in the clinic before and during the pandemic were identified in DANBIO [all patients and subgroups with early disease (disease duration ≤2 years)]. In individual patients, changes in PROs before and during the pandemic were calculated. Characteristics of patients with/without physical consultations were described (age, gender, education level, comorbidities, disease duration, treatment). RESULTS: We included 7836 patients (22% of eligible patients), 12% of which had early disease. PROs were stable before and during the pandemic, with median changes approximating zero, as well as in patients with early disease. Remission rates were stable. The relative decrease in the number of patients with physical consultations was 21-72%, which was highest in axSpA. Characteristics of patients with/without physical consultations were similar. Self-reported satisfaction with treatment options and access was >70%; the preferred contact form was physical consultation (66%). CONCLUSION: In this nationwide study performed during the first 8 months of the pandemic, patient satisfaction was high and the PROs and remission rates remained stable despite the remarkable reduction in physical consultations, as well as in patients with early disease. Characteristics of patients with/without physical consultations appeared similar.

Conical versus Gaussian terahertz emission from two-color laser-induced air plasma filaments.

In this Letter, we demonstrate that the far-field terahertz (THz) beam generated from a Ti:Sapphire two-color laser-induced filament can exhibit a conical or Gaussian distribution, depending on the filtering experimental conditions. Using both an incoherent Golay cell detector and a two-dimensional coherent electro-optic detection covering the 0.2-2.6 THz spectral range, in our experimental conditions, we provide evidence that the conical emission is due to photo-induced carriers in the silicon filter, typically used to block the remaining pump laser light. Moreover, the low-frequency THz beam retrieves an almost $ {{\rm TEM}_{00}} $TEM00 Gaussian spatial distribution when the silicon filter is preceded by a large bandgap ceramic filter, which stops the pump beam, thus preventing the carrier generation in the silicon filter.

A nationwide registry-based cohort study of incidence of tonsillectomy in Denmark, 1991-2012.

OBJECTIVE: To update tonsillectomy incidence rates in Denmark and identify whether the incidence rates vary between geographical areas in the country during the period 1991-2012. DESIGN: This was a retrospective nationwide cohort study using data from the comprehensive Danish patient registries. Data included surgical code, gender and date of birth, date and place of surgery. SETTING: Hospitals and private oto-, rhino-, laryngology (ORL) offices. PARTICIPANTS: Danes who underwent tonsillectomy in the period 1991-2012. MAIN OUTCOME MEASURE: Tonsillectomy. RESULTS: In the 22-year period, 177 211 tonsillectomies were conducted, and the overall incidence of tonsillectomy decreased significantly over time. The overall annual incidence of tonsillectomies decreased from 155.7 per 100 000 inhabitants in 1991 to 129.4 per 100 000 inhabitants in 2012. In 1991, 5.5% of tonsillectomies were performed in office settings, while in 2012, it had increased to 26.6% (P < .01). The highest incidence of tonsillectomy was found in children between 3 and 4 years of age (predominance of males, P < .01) and in 15- to 19-year-olds (predominance of females, P < .01). Each year, 0.44% of children underwent tonsillectomy, and by the age of 20, 7.7% of the Danish people has had a tonsillectomy. There were significant regional differences in the number of tonsillectomies. CONCLUSION: The incidence rate of tonsillectomies in Denmark decreased significantly in the study period, but with great regional variance.

Risk factors for recurrent nerve palsy after thyroid surgery: a national study of patients treated at Danish departments of ENT Head and Neck Surgery.

Recurrent laryngeal nerve (RLN) injury is a well-known and serious complication to thyroid surgery. The objective was to estimate the frequency of post-thyroidectomy RLN palsy and to identify possible risk factors. Based on the Danish national thyroid surgery database, 6,859 patients treated with thyroid surgery from 1 January 2001 to the 31 December 2008 at the Danish departments of ENT-HNS were analyzed. Unilateral RLN palsy was found in 2.1 % and bilateral in 0.1 %. In benign histology, RLN palsies were registered in 1.3 %. Malignant histology and accordingly neck dissection were the most predominant risk factors with a relative risk (RR) of 5.4 and 5.8, respectively. In benign cases previous performed thyroid surgery had a RR of 10.4. High volume departments with more than 150 thyroid procedures per year seem to perform significantly better. Malignant histology, neck dissection and previous performed thyroid surgery are the strongest predictors for RLN palsy and patient information should be given accordingly. Incomplete resections should be reserved for isthmectomy only. Centralization of thyroid surgery in larger units might improve quality.

Is Left-Handedness Associated With Greater Success From the 7-Meter Line? An Analysis of 7-Meter Records Across Various Handball Competitions.

While left-handers have been overrepresented among 7-meter shooters in handball, previous investigators have not found success from the 7-meter line to be related to handedness. Drawing on previous handedness research in sport, we performed two studies to examine possible negative frequency-dependent advantages to left-handedness during 7-meter throws among elite players. In Study I, we analyzed the records of 974 7-meter shooters from Danish and Norwegian elite divisions (485 males and 489 females) and found that left-handed males were overrepresented compared to the prevalence of left-handers in these two leagues, but left-handed females were not. An analysis of covariance showed no statistically significant associations between throwing arm or sex, and success from the 7-meter line. In Study II, we analyzed the records of 899 7-meter shooters at 41 major championships for both males and females between 2007-2023 (442 males and 457 females). We again found left-handed males to be overrepresented compared to their prevalence at the championships, but left-handed females were not. Also, in alignment with Study I, an analysis of covariance found no associations between throwing arm or sex, and success from 7-meter throws. These findings further underline the complexities associated with lateral biases in sports, where there appear to be benefits for left-handed males in the selection process that are not evident during performance execution.

Dataset of smart heat and water meter data with accompanying building characteristics.

The data presented were sourced from 34,884 commercial smart heat meters and 10,765 commercial smart water meters, spanning a timeframe of up to 5 years (2018-2022). All data primarily originated from single-family houses in Aalborg Municipality, Denmark. Furthermore, comprehensive building characteristics were collected for each building, where available, from the Danish Building and Dwelling Register (BBR) and Energy Performance Certificate (EPC) input data. This effort yielded an extensive pool of up to 86 distinct characteristics per building. All smart meter data were processed employing a well-established methodology, resulting in equidistant hourly data without any erroneous or missing values. The building characteristics derived from the EPCs were additionally filtered using rule sets to improve the data quality. This dataset holds substantial value for researchers involved in the domains of the built environment, district heating, and water sectors.

Suppression of TCF4 promotes a ZC3H12A-mediated self-sustaining inflammatory feedback cycle involving IL-17RA/IL-17RE epidermal signaling.

IL-17C is an epithelial cell-derived proinflammatory cytokine whose transcriptional regulation remains unclear. Analysis of the IL17C promoter region identified TCF4 as putative regulator, and siRNA knockdown of TCF4 in human keratinocytes (KCs) increased IL17C. IL-17C stimulation of KCs (along with IL-17A and TNF-α stimulation) decreased TCF4 and increased NFKBIZ and ZC3H12A expression in an IL-17RA/RE-dependent manner, thus creating a feedback loop. ZC3H12A (MCPIP1/Regnase-1), a transcriptional immune-response regulator, also increased following TCF4 siRNA knockdown, and siRNA knockdown of ZC3H12A decreased NFKBIZ, IL1B, IL36G, CCL20, and CXCL1, revealing a proinflammatory role for ZC3H12A. Examination of lesional skin from the KC-Tie2 inflammatory dermatitis mouse model identified decreases in TCF4 protein concomitant with increases in IL-17C and Zc3h12a that reversed following the genetic elimination of Il17c, Il17ra, and Il17re and improvement in the skin phenotype. Conversely, interference with Tcf4 in KC-Tie2 mouse skin increased Il17c and exacerbated the inflammatory skin phenotype. Together, these findings identify a role for TCF4 in the negative regulation of IL-17C, which, alone and with TNF-α and IL-17A, feed back to decrease TCF4 in an IL-17RA/RE-dependent manner. This loop is further amplified by IL-17C-TCF4 autocrine regulation of ZC3H12A and IL-17C regulation of NFKBIZ to promote self-sustaining skin inflammation.

LigaSure small jaws versus cold knife dissection in superficial parotidectomy.

The objective of this study was to evaluate the use of LigaSure small jaws in superficial parotidectomy for blood loss, operative time and facial nerve function. This was a prospective non-randomized study of 35 patients with a benign parotid tumor. Sixteen patients had LigaSure small jaws parotidectomy, and 19 patients had cold knife parotidectomy. Operative time, blood loss, facial palsy and other complications were assessed. The use of LigaSure was associated with a significant reduction in mean operative time (128 min vs. 155, p = 0.04) and intraoperative blood loss (40 mL vs. 115 mL, p < 0.001). Transient facial weakness was seen in 4 of the 16 patients in the LigaSure group and in 1 of the 19 patients in the conventional group (p = 0.2). No significant differences were observed between the two groups with respect to hemorrhage, length of hospital stay, infection, wound healing, salivary fistula or seroma. LigaSure small jaws in parotidectomy results in significantly less blood loss and operative time compared to cold knife dissection.

Exhaled nitric oxide in intubated ICU patients on mechanical ventilation-a feasibility study.

It can be a clinical challenge to distinguish inflammation from infection in critically ill patients. Therefore, valid and conclusive surrogate markers for infections are desired. Nitric oxide (NO) might be that marker since concentrations of exhaled NO have shown to change in the presence of various diseases. This observational, prospective, single-center feasibility study aimed to investigate if fractional exhaled NO (FeNO) can be measured in intubated patients with or without infection, pneumonia and septic shock in a standardized, reliable setting. 20 intubated patients in the intensive care unit (ICU) were included for analysis. FeNO mean values were measured in the endotracheal tube via the suction channel using a chemiluminescence based analyzer. We developed a pragmatic method to measure FeNO repeatedly and reliably in intubated patients using a chemiluminescence based analyzer. We found a median of 0.98 (0.59-1.44) FeNO mean (ppb) in exhaled breath from all 20 intubated patient. Intubated patient with suspected infection had a significantly lower median FeNO mean compared with the intubated patients without suspected infection. Similarly did patients with septic shock demonstrate a significantly lower median FeNO mean than without septic shock. We found no statistical difference in median FeNO mean for intubated patients with pneumonia. It was feasible to measure FeNO in intubated patients in the ICU. Our results indicate decreased levels of FeNO in infected intubated patients in the ICU. The study was not powered to provide firm conclusions, so larger trials are needed to confirm the results and to prove FeNO as a useful biomarker for distinguishment between infection and inflammation in the ICU.

Risk of marginal mandibular nerve injury in neck dissection.

The immediate and permanent frequency of injury to the marginal mandibular branch of the facial nerve (MMN) after neck dissection has only scarcely been addressed in the medical literature. We investigated the risk of injury in 159 consecutive patients after neck dissection for various reasons in level I B and level II A, respectively. In 95 patients with oral cancer 13 (14%) of the cases had malfunction of the lower lip domain 2 weeks after neck dissection in level I B indicating paresis to the MMN. Follow-up analyses 1-2 years after the operation showed permanent paralysis in 4 to 7% of the cases in whom two of them had the nerve sacrificed for oncologic reasons during the operation. In 18 patients with parotic cancer the corresponding permanent frequency of MMN paralysis was 11.1%. In 46 patients with neck dissection in level II A but not in level I B, no paresis of the MMN was registered. Recognition of the MMN during the operation, pre- or postoperative radiation therapy, re-operation for deep hemorrhage, age, gender or postoperative infection did not have any statistically significant influence on the frequency of MMN injury. In conclusion we found a moderate risk of injury to the MMN after neck dissection in level I B whereas the corresponding risk after level II A dissection was negligible.

Quality of life, voiding and sexual function of penile cancer patients: DaPeCa-10-a cross-sectional questionnaire survey.

Objectives: To assess prevalence of voiding and sexual symptoms and quality of life in penile cancer patients. Methods: From 1 January 2013 to 31 December 2015, we approached three separate groups of Danish penile cancer patients and asked them to complete a face-validated questionnaire at diagnosis (Group 1), after 1 year (Group 2) and after 2 years (Group 3). We analysed symptom prevalence and bother and quality of life items and explored differences between groups. Results: In total, we analysed 157 questionnaires. The response rates at diagnosis, after 1 year and after 2 years were 29%, 46% and 30%. The pad use (p = 0.001) and occurrence of nocturia twice a night or more (p = 0.006) was significantly decreasing 2 years after treatment. There was an increasing trend in sexual thoughts and importance of sexuality from 1 to 2 years after treatment, but the proportion of patients reporting a frequency of orgasm at more than once in the past 6 months was significantly decreasing after treatment (p = 0.03). Likewise, the trend for erectile dysfunction worsened after treatment with 49% of patients reporting an erection never sufficient for intercourse at diagnosis increasing to 62% after 1 year and 69% after 2 years. We observed trends towards lower self-esteem with increasingly mutilating treatment. Conclusion: Pad use, nocturia and frequency of orgasm were significantly reduced after penile cancer treatment. We observed trends towards lower self-esteem with increasingly mutilating treatment and increase in erectile dysfunction after treatment.

Endotracheal lactate reflects lower respiratory tract infections and inflammation in intubated patients.

The aim of this study was to assess L-lactate and D-lactate in endotracheal aspirate from intubated patients hospitalized at the intensive care unit and explore their use as diagnostic biomarkers for inflammation and lower respiratory tract infections (LRTI). Tracheal aspirates from 91 intubated patients were obtained at time of intubation and sent for microbiological analyses, neutrophil count, and colorimetric lactate measurements. We compared the concentration of lactate from patients with microbiological verified LRTI or clinical/radiological suspicion of LRTI with a control group. In addition, associations between inflammation and the lactate isomers were examined by correlating L-lactate and D-lactate with sputum neutrophils and clinical assessments. The concentration of L-lactate was increased in aspirates with verified or suspected LRTI (p < 0.001) relative to the control group at Day 0. Connections between L-lactate and inflammation were indicated by the correlation between neutrophils and L-lactate (p < 0.001). We found no increase in sputum D-lactate from patients with verified or suspected LRTI relative to the control group and D-lactate was not correlated with neutrophils. L-lactate was found to be a potential indicator for inflammation and LRTI at the time of intubation. An association was found between neutrophil count and L-lactate. Interestingly, the increase of L-lactate in the control group after intubation may suggest that intubation challenges the host response by inflicting tissue damage or by introducing infectious microbes.

Nationwide, large-scale implementation of an online system for remote entry of patient-reported outcomes in rheumatology: characteristics of users and non-users and time to first entry.

AIMS: In May 2020, a nationwide, web-based system for remote entry of patient-reported outcomes (PROs) in inflammatory rheumatic diseases was launched and implemented in routine care (DANBIO-from-home). After 1.5 years of use, we explored clinical characteristics of patients who did versus did not use the system, and the time to first entry of PROs. METHODS: All patients followed in DANBIO were informed about DANBIO-from-home by electronic invitations or when attending their clinic. Characteristics of patients who did/did not use DANBIO-from-home in the period after implementation were explored by multivariable logistic regression analyses including demographic and clinical variables (gender, age group, diagnosis, disease duration, use of biological disease-modifying agent (bDMARD), Health Assessment Questionnaire (HAQ), Patient Acceptable Symptom Scale (PASS)). Time from launch to first entry was presented as cumulative incidence curves by age group (<40/40-60/61-80/>80 years). RESULTS: Of 33 776 patients, 68% entered PROs using DANBIO-from-home at least once. Median (IQR) time to first entry was 27 (11-152) days. Factors associated with data entry in multivariate analyses (OR (95% CI)) were: female gender (1.19 (1.12 to 1.27)), bDMARD treatment (1.41 (1.33 to 1.50)), age 40-60 years (1.79 (1.63 to 1.97)), 61-80 years (1.87 (1.70 to 2.07), or age >80 years (0.57 (0.50 to 0.65)) (reference: age <40 years), lower HAQ (0.68 (0.65 to 0.71)) and PASS 'no' (1.09 (1.02 to 1.17). Diagnosis was not associated. Time to first entry of PROs was longest in patients <40 years of age (119 (24-184) days) and shortest in the 61-80 years age group (25 (8-139) days). CONCLUSION: A nationwide online platform for PRO in rheumatology achieved widespread use. Higher age, male gender, conventional treatment and disability were associated with no use.

Long-term Behavioral Changes During the COVID-19 Pandemic and Impact of Vaccination in Patients With Inflammatory Rheumatic Diseases.

OBJECTIVE: To explore anxiety and self-isolation in patients with inflammatory rheumatic disease (IRD)15 months into the coronavirus disease 2019 (COVID-19) pandemic, including attitudes toward and effects of SARS-CoV-2 vaccination. METHODS: A nationwide online survey was conducted at 3 timepoints: May 2020, November 2020, and May 2021. Patients with IRD followed in the Danish Rheumatology Quality Registry (DANBIO) were asked about the effects of the pandemic, including SARS-CoV-2 infection and their behavior, anxiety, and concerns. The May 2021 survey included attitudes toward SARS-CoV-2 and influenza vaccination. Characteristics associated with self-isolation in May 2021 were explored with adjusted logistic regression analyses that included patient characteristics and SARS-CoV-2 vaccination status. RESULTS: Respondents to surveys 1, 2, and 3 included 12,789; 14,755; and 13,921 patients, respectively; 64% had rheumatoid arthritis and 63% were female. Anxiety and concerns were highest in May 2020 and decreased to stable levels in November 2020 and May 2021; 86%, 50%, and 52% of respondents reported self-isolation, respectively. In May 2021, 4% of respondents self-reported previous SARS-CoV-2 infection. The SARS-CoV-2 vaccine acceptance rate was 86%, and the proportion of patients vaccinated against influenza had increased from 50% in winter 2019-2020 to 64% in winter 2020-2021. The proportion of patients with anxiety appeared similar among those vaccinated and unvaccinated against SARS-CoV-2. In multivariable analyses, being unvaccinated, female gender, receiving biologic drugs, and poor quality of life were independently associated with self-isolation. CONCLUSION: Levels of anxiety and self-isolation decreased after the initial lockdown period in patients with IRD. Half of the patients reported self-isolation in May 2021, a phase that included widespread reopening of society and large-scale vaccination. The lack of prepandemic data prevented a full understanding of the long-term effects of the pandemic on anxiety and self-isolation in patients with IRD.

Bimodal ex vivo expansion of T cells from patients with head and neck squamous cell carcinoma: a prerequisite for adoptive cell transfer.

BACKGROUND AIMS: Adoptive transfer of tumor-infiltrating lymphocytes (TIL) has proven effective in metastatic melanoma and should therefore be explored in other types of cancer. The aim of this study was to examine the feasibility of potentially expanding clinically relevant quantities of tumor-specific T-cell cultures from TIL from patients with head and neck squamous cell carcinoma (HNSCC) using a more rapid expansion procedure compared with previous HNSCC studies. METHODS: In a two-step expansion process, initially TIL bulk cultures were established from primary and recurrent HNSCC tumors in high-dose interleukin (IL)-2. Secondly, selected bulk cultures were rapidly expanded using anti-CD3 antibody, feeder cells and high-dose IL-2. T-cell subsets were phenotypically characterized using flow cytometry. T-cell receptor (TCR) clonotype mapping was applied to examine clonotype dynamics during culture. Interferon (INF)-γ detection by Elispot and Cr(51) release assay determined the specificity and functional capacity of selected TIL pre- and post-rapid expansion. RESULTS: TIL bulk cultures were expanded in 80% of the patients included, showing tumor specificity in 60% of the patients. Rapid expansions generated up to 3500-fold expansion of selected TIL cultures within 17 days. The cultures mainly consisted of T-effector memory cells, with varying distributions of CD8(+) and CD4(+) subtypes both among cultures and patients. TCR clonotype mapping demonstrated oligoclonal expanded cultures, ranging from approximately 10 to 30 T-cell clonotypes. TIL from large-scale rapid expansions maintained functional capacity, and contained tumor-specific T cells. CONCLUSION: The procedure is feasible for expansion of TIL from HNSCC, ensuring clinically relevant expansion folds within 7 weeks. The cell culture kinetics and phenotypes of the TIL resemble previously published results on TIL from melanoma, setting the stage for clinical testing of this promising treatment strategy for patients with HNSCC.

Need for thyroidectomy in patients treated with radioactive iodide for benign thyroid disease.

INTRODUCTION: Nodular toxic and non-toxic goitres are seen in approximately 15% of Danish women, and the pros and cons of thyroidectomy versus radioiodine (RI) therapy are often discussed. The purpose of this study was to evaluate the type and number of patients treated on the indication of hyperthyroidism or benign goitre who did not achieve a sufficient effect of RI therapy and therefore needed thyroidectomy. MATERIAL AND METHODS: Between 1 January 2003 and 1 January 2008, a total of 873 patients were treated with RI on the indication of benign thyroid disease at Herlev Hospital (Denmark). Data concerning these patients were listed consecutively in a database. The data were subsequently cross-checked with the Danish Thyroid Surgery Quality Register (THYKIR) which contains data on all patients treated with thyroid surgery at Danish departments of ear, nose and throat and head and neck surgery since 1 January 2001. Patient data were also cross-checked with the National Patient Register data. The unique Danish social security numbers were used to compare data. RESULTS: Among the 873 patients treated with RI, 36 were listed in the THYKIR database. Eleven of these had primary thyroid surgery and subsequently underwent RI treatment due to goitre recurrence. Twenty-five patients first received RI therapy and subsequently thyroidectomy due to persisting symptoms (17 had non-toxic goitre and compression symptoms (among these eight had a large goitre with a thyroid volume of > 100 ml (range 100-389 ml)), five had nodular toxic goitre and three had diffuse toxic goitre and continuing hyperthyroidism despite RI treatment. Thyroid surgery revealed a small (2-3 mm) cancer in two patients, both from the group of patients with nodular toxic goitre. CONCLUSION: The effect of RI therapy sufficiently solved the problem (hyperthyroidism or goitre) and surgery was hence avoided in 848 of 873 (97%) patients. However, within the group of patients with nontoxic goitre, a subgroup of patients with large goitres seems to be resistant to RI treatment and does not achieve sufficient effect under the current RI therapy regime. FUNDING: not relevant. TRIAL REGISTRATION: Danish Data Protection Agency (Datatilsynet) HEH.afd.O.750.86-7 and 2010-231-0068.

Reversibility of oxalate nephropathy in a kidney transplant recipient with prior gastric bypass surgery.

Bariatric surgery is an acknowledged treatment for obesity and related comorbidities with beneficial effects on kidney function. However, bariatric surgery can also lead to secondary hyperoxaluria and oxalate nephropathy, resulting in end-stage kidney disease in both native and transplanted kidneys. We present a 66-year-old man who was in need of dialysis 3 months after kidney transplantation due to recurrent oxalate nephropathy. Intensified haemodialysis together with increased liquid intake, dietary restrictions of oxalate and fat and supplementation with calcium citrate and a bile acid binder were applied. Graft function improved and the patient did not require dialysis during the following 8 months.