Prevalence of metastases outside the liver and abdominal lymph nodes on 68Ga-DOTATOC-PET/CT in patients with small intestinal and pancreatic neuroendocrine tumours.

Metastases outside the liver and abdominal/retroperitoneal lymph nodes are nowadays detected frequently in patients with neuroendocrine tumours (NETs), owing to the high sensitivity of positron emission tomography (PET) with Gallium-68-DOTA-somatostatin analogues (68Ga-SSA) and concomitant diagnostic computed tomography (CT). Our aim was to determine the prevalence of extra-abdominal metastases on 68Ga-DOTATOC-PET/CT in a cohort of patients with small intestinal (Si-NET) and pancreatic NET (Pan-NET), as well as that of pancreatic metastasis in patients with Si-NET. Among 2090 patients examined by 68Ga-DOTATOC-PET/CT at two tertiary referral centres, a total of 1177 patients with a history of Si- or Pan-NET, were identified. The most recent 68Ga-DOTATOC-PET/CT report for each patient was reviewed, and the location and number of metastases of interest were recorded. Lesions outside the liver and abdominal nodes were found in 26% of patients (n = 310/1177), of whom 21.5% (255/1177) were diagnosed with Si-NET and 4.5% (55/1177) Pan-NET. Bone metastases were found in 18.4% (215/1177), metastases to Virchow's lymph node in 7.1% (83/1177), and lung/pleura in 4.8% (56/1177). In the subset of 255 Si-NET patients, 5.4% (41/255) manifested lesions in the pancreas, 1.5% in the breast (18/255), 1.3% in the heart (15/255) and 1% in the orbita (12/255). In Si-NET patients, the Ki-67 proliferation index was higher in those with ≥2 metastatic sites of interest, than with 1 metastatic site, (p <0.001). Overall, extra-abdominal or pancreatic metastases were more often found in patients with Si-NET (34%) than in those with Pan-NET (13%) (p <0.001). Bone metastases were 2.6 times more frequent in patients with Si-NET compared to Pan-NET patients (p <0.001). Lesions to the breast and orbita were encountered in almost only Si-NET patients. In conclusion, lesions outside the liver and abdominal nodes were detected in as many as 26% of the patients, with different prevalence and metastatic patterns in patients with Si-NET compared to Pan-NET. The impact of such metastases on overall survival and clinical decision-making needs further evaluation.

Modified Histopathological Grading Optimizes Prediction of Survival Outcomes in Small Intestinal Neuroendocrine Tumours.

CONTEXT: One of the major prognostic indices in neuroendocrine tumours (NETs) is Ki67 proliferation index. OBJECTIVE: To identify optimal grading Ki-67 cut-offs to delineate differences in prognosis of patients with small intestinal NETs (SI-NETs). DESIGN, SETTING, PARTICIPANTS: Multicentre retrospective cohort analysis of 551 SI-NET patients diagnosed from 1993 through 2021 at five European referral centres with a mean(±SD) follow-up time of 51.5(±52.9) months. MAIN OUTCOME MEASURES: Overall- and event-free survival (OS and EFS) rates. RESULTS: Median age at baseline was 62.3(range:17-90) years; 252(45.7%) patients were female. All SI-NETs were well-differentiated with 326 being grade 1(G1; 59.2%), 169G2(30.7%), and only 8G3(1.5), while 48 tumours were of unspecified grade (8.7%). The median Ki67 was 2%(range:1-70%). Two-hundred forty-seven patients (44.8%) had distant metastases at baseline (stage IV), 217 locoregional disease (41.1%; stage III), whereas 29(7.1%) and 25(4.5%) presented at stages II and I, respectively. The median OS was 214.7(95%CI:152.7-276.6) months and the median EFS was 79.8(95%CI:68.2-91.5) months, respectively. In multivariable Cox-regression OS analysis, the proposed modified histopathological Ki67 grading system (K67:5-10% group: HR=2.2, 95%CI:1.15-4.31; p=0.018 and K67≥10% group: HR=5.11, 95%CI:2.87-9.09; p<0.001), age (HR=1.07, 95%CI:1.04-1.09; p<0.001), Charlson Comorbidity Index (HR=1.08, 95%CI:1-1.16; p=0.028) and TNM stage (HR=1.79, 95%CI:1.05-3.06; p=0.034) were independent predictors for death. Pertinent EFS analysis, confirmed the proposed modified histopathological Ki67 grading system (K67≥10% group: HR=4.01, 95%CI:2.6-6.37; p<0.001) and age (HR=1.04, 95%CI:1.02-1.05; p<0.001) as independent predictors for recurrence, progression and/or death. CONCLUSIONS: Ki-67 proliferation index was a strong and independent predictor of OS and EFS. A modified histopathological grading system applying Ki-67 cut-offs of 5 and 10% could be superior to predict differences in SI-NET patient survival outcomes.

Impact of fine-needle aspiration cytology in thyroidectomy extent and associated surgical morbidity in thyroid cancer.

PURPOSE: To assess the impact of fine-needle aspiration cytology (FNAC) in the extent of surgery in patients with thyroid cancer (TC) and the associated surgical morbidity in primary and completion setting. METHODS: A Swedish nationwide cohort of patients having surgery for TC (n = 2519) from the Scandinavian Quality Register for Thyroid, Parathyroid and Adrenal surgery between 2004 and 2013 was obtained. Data was validated through scrutinizing FNAC and histology reports. RESULTS: Among the 2519 cases operated for TC, the diagnosis was substantiated and validated through the histology report in 2332 cases (92.6%). Among these, 1679 patients (72%) were female, and the median age at TC diagnosis was 52.3 years (range 18-94.6). Less than total thyroidectomy (LTT) was undertaken in 944 whereas total thyroidectomy (TT) in 1388 cases. The intermediate FNAC categories of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/ FLUS), as well as suspicion for follicular neoplasm (SFN) lesions were more often encountered in LTT (n = 314, 33.3%) than TT (n = 63, 4.6%), whereas FNACs suspicion for malignancy and/or malignancy were overrepresented in TT (n = 963, 69.4%). Completion thyroidectomies were undertaken in 553 patients out of 944 that initially had LTT. In 201 cases with cancer lesions > 1 cm, other than FTC (Follicular TC)/ HTC (Hürthle cell TC) subjected to primary LTT, inadequate procedures were undertaken in 81 due to absent, Bethesda I or II FNAC categories, preoperatively. Complications at completion of surgery in this particular setting were 0.5% for RLN palsy (n = 1) and 1% (n = 2) for hypoparathyroidism 6 months postoperatively. The overall postoperative complication rate was higher in primary TT vs. LTT for RLN palsy (4.8% [n = 67] vs. 2.4% [n = 23]; p = 0.003) and permanent hypoparathyroidism (6.8% [n = 95] vs. 0.8% [n = 8]; p < 0.0001). CONCLUSIONS: FNAC results appear to affect surgical planning in TC as intermediate FNAC categories lead more often to LTT. Overall, inadequate procedures necessitating completion surgery are encountered in up to 15% of TC patients subjected to LTT due to absent, inconclusive, or misleading FNAC, preoperatively. However, completion of thyroidectomy in this setting did not yield significant surgical morbidity. Primary LTT is a safer primary approach compared to TT in respect of RLN palsy and permanent hypoparathyroidism complication rates; therefore, primary TT should probably be reserved for lesions > 1 cm or even larger with suspicion for malignancy or malignant FNAC.

Validating the risk of hypoparathyroidism after total thyroidectomy in a population-based cohort: plea for improved follow-up.

BACKGROUND: A previous nationwide study from Sweden showed that the rate of permanent hypoparathyroidism is high and under-rated in the Swedish Quality Register. This retrospective population-based study aimed to validate the rate and diagnosis of permanent hypoparathyroidism found in the previous study. A secondary aim was to assess the relationship between the rate of low parathyroid hormone (PTH) levels within 24 h after surgery and the rate of permanent hypoparathyroidism. METHODS: All patients who underwent total thyroidectomy from 2005 to 2015 in a region of Sweden were included. Data were retrieved from local health records, the National Patient Registry, the Swedish Prescribed Drug Registry, and the Swedish Quality Register. A strict definition of permanent hypoparathyroidism was used, including biochemical data and attempts to stop the treatment. RESULTS: A total of 1636 patients were included. Altogether, 143 patients (8.7 per cent) developed permanent hypoparathyroidism. Of these, 102 (6.2 per cent) had definitive permanent hypoparathyroidism, whereas 41 (2.5 per cent) had possible permanent hypoparathyroidism, because attempts to stop the treatment were lacking (28) or patients were lost to follow-up (13). The agreement between the Swedish Quality Register and the chart review was 29.3 per cent. A proportion of 23.2 per cent with a PTH level below the reference value corresponded to a 6.7 per cent rate of permanent hypoparathyroidism. CONCLUSION: The risk of permanent hypoparathyroidism after total thyroidectomy is high. Some patients are overtreated because attempts to stop the treatment are lacking. Quality registers might underestimate the risk of permanent hypoparathyroidism. Approximately one-quarter of all patients with low PTH levels immediately after surgery developed permanent hypoparathyroidism.

The parathyroid glands control calcium levels in the blood. If they do not make enough hormone, calcium levels are low. Parathyroid dysfunction can happen after thyroid surgery, if the glands are hurt or removed by mistake. This is a problem because people with this condition may have symptoms and need ongoing treatment with vitamin D and calcium. They might also face other health issues and need regular visits to their doctor. Finding out how often long-term parathyroid dysfunction happens can be tricky because it requires a full year of follow-up and attempts to stop the treatment. This information is often missing from many studies and registers. Some recent studies have shown that this condition is more common than previously thought. It would be helpful to have a quick way to know how common long-term parathyroid gland dysfunction will be within a unit or hospital, without having to wait for the follow-up. This would help doctors to assess how good they are at taking care of patients. It would also support research on new methods to avoid parathyroid dysfunction. The goal of the study was to see how often long-term parathyroid dysfunction occurs after thyroid surgery, using a strict definition and complete long-term follow-up. Another aim was to assess the link between low parathyroid hormone levels right after surgery and the rate of long-term parathyroid dysfunction. All individuals who had the entire thyroid gland removed for benign disease between 2005 and 2015 in a region of Sweden were included. Data were collected from local health records at six hospitals. Patient information, surgical details, blood tests, and treatment details were gathered from the medical charts. Data were also collected from the national quality register. A high rate of long-term parathyroid dysfunction was seen in this large study of 1636 patients, Some patients may have been overtreated, because no attempts had been made to stop the treatment. The rate of long-term parathyroid dysfunction in patients with a normal early parathyroid hormone level was very low. About 23 per cent of all patients had a low early parathyroid hormone level, which corresponded to a 6.7 per cent rate of long-term parathyroid dysfunction. The authors believe that parathyroid hormone measurement could help predict the rate of permanent hypoparathyroidism, but more studies are needed to be sure.

Long-Term Outcome of Graves' Disease: A Gender Perspective.

Introduction: In gender-skewed conditions such as Graves' disease (GD), the outcome naturally becomes dominated by the majority. This may lead to gender-biased misunderstandings regarding treatment outcomes. This especially holds true when complications, such as depression, are unevenly distributed. We have, therefore, studied the long-term outcome of GD from a gender perspective. Materials and Methods: A cohort of 1186 patients with GD was included in a follow-up 6-10 years after inclusion. Choice of treatment, the feeling of recovery, long-term treatment, comorbidity, and quality of life were investigated with questionnaires. All results were studied sex-divided. Results: We included 973 women and 213 men. There was no difference between men and women in the choice of treatment. At follow-up, women scored significantly worse in the general questionnaire 36-item Short-Form Health Status (SF-36) domain bodily pain and in the thyroid-specific Thyroid-Related Patient-Reported Outcome (ThyPRO) domains depression, impaired sex life, and cosmetic complaints, all p < 0.05. Women were twice as likely (29.5%) to be treated with levothyroxine after successful treatment with antithyroid drugs (ATD) compared with men (14.9%, p < 0.05). Conclusion: After treatment for GD, women were more affected by depression, impaired sex life, cosmetic issues, and bodily pain despite successful cure of hyperthyroidism. The prevalence of hypothyroidism was also doubled in women. Whether these observed gender differences reflect a worse outcome of GD in women or a natural consequence of a higher prevalence of these symptoms and autoimmunity in the female population is difficult to disentangle. Nevertheless, several years after GD, women reveal more persistent symptoms.

Fracture Incidence in Graves' Disease: A Population-Based Study.

Background: Population-based studies have indicated an increase in bone turnover in hyperthyroidism with a subsequent decrease in bone mineral density and an increased risk of fractures, especially in postmenopausal women. However, heterogeneity between studies prevents a definitive conclusion. Graves' disease (GD) is an autoimmune disease, and it is the most common cause of hyperthyroidism. The aim of this study was to investigate fracture risk in patients with GD. Methods: A total of 2134 patients with incident GD and 21,261 age, sex- and county-matched controls were included 16-18 years after diagnosis in a retrospective cohort study. Drug and patient national registries in Sweden were used to assess the risk of developing skeletal complications. Up to 10 years of age, sex- and county-matched controls per patient were selected from databases from the National Board of Health and Welfare and Statistics Sweden. Cox proportional hazards models were fitted to estimate hazard ratios (HR) and confidence intervals [CI]. Results: There were no significant differences in fracture rates between GD and controls but after adjustment for comorbidities, the data showed higher vertebral fracture rates in male GD patients aged >52 years compared to male controls, HR = 2.83 [CI 1.05-7.64]. The rates of osteoporosis treatments as well as treatment with corticosteroids were higher in patients with GD. However, HR for the association between GD and fractures remained largely unchanged after adjustment for osteoporosis treatments and treatments with corticosteroids. Conclusions: There were no significant differences in total fracture rate between GD and the general population. However, men older than 52 years had a higher vertebral fracture rate. This study also shows that patients with treated GD receive more osteoporosis treatments compared to the general population.

Peritoneal Bridging Versus Nonclosure in Laparoscopic Ventral Hernia Repair: A Randomized Controlled Trial.

Introduction: Postoperative seroma and pain are common problems following laparoscopic intraperitoneal onlay mesh (IPOM) repair of ventral hernias. These adverse outcomes may be avoided by dissecting and using the peritoneum in the hernial sac to bridge the hernia defect. Methods: This was a patient- and outcome assessor-blinded, parallel-design, randomized controlled trial comparing nonclosure and peritoneal bridging approaches in patients scheduled for elective midline ventral hernia repair. The primary endpoint was seroma volume on ultrasonography. The secondary endpoints were postoperative pain, recurrence, and complications. Results: Between November 2018 and December 2020, 112 patients were randomized, of whom 60 were in the nonclosure group and 52 were in the peritoneal bridging group. The seroma volume in the nonclosure and peritoneal bridging groups were 17 cm3 (6-53 cm3) versus 0 cm3 (0-26 cm3) at 1-month follow-up (P = 0.013). The median volume was zero at the 3-, 6-, and 12-month follow-ups in both groups. No significant differences were observed in early postoperative pain (P = 0.447) and in recurrence rate (P = 0.684). There were 4 (7%) and 1 (2%) perioperative complications that lead to reoperations in simple IPOM (sIPOM) and IPOM with peritoneal bridging (IPOM-pb), respectively. Conclusions: Seroma was less prevalent after IPOM-pb at 1-month follow-up compared with sIPOM, with similar postoperative pain 1 week after index surgery in both groups. At subsequent follow-ups, the differences in seroma were not statistically significant. Further studies are required to confirm these results. Trial registration (NCT04229940).

Effect of the SARS-CoV-2 pandemic on planned and emergency hernia repair in Sweden: a register-based study.

PURPOSE: The COVID-19 has had a profound impact on the health care delivery in Sweden, including deprioritization of benign surgeries during the COVID-19 pandemic. The aim of this study was to assess the effect of COVID-19 pandemic on emergency and planned hernia repair in Sweden. METHODS: Data on hernia repairs from January 2016 to December 2021 were retrieved from the Swedish Patient Register using procedural codes. Two groups were formed: COVID-19 group (January 2020-December 2021) and control group (January 2016-December 2019). Demographic data on mean age, gender, and type of hernia were collected. RESULTS: This study showed a weak negative correlation between the number of elective hernia repairs performed each month during the pandemic and the number of emergency repairs carried out during the following 3 months for inguinal hernia repair (p = 0.114) and incisional hernia repair (p = 0.193), whereas there was no correlation for femoral or umbilical hernia repairs. CONCLUSION: The COVID-19 pandemic had a great impact on planned hernia surgeries in Sweden, but our hypothesis that postponing planned repairs would increase the risk of emergency events was not supported.

Components explain, but do eddy fluxes constrain? Carbon budget of a nitrogen-fertilized boreal Scots pine forest.

Nitrogen (N) fertilization increases biomass and soil organic carbon (SOC) accumulation in boreal pine forests, but the underlying mechanisms remain uncertain. At two Scots pine sites, one undergoing annual N fertilization and the other a reference, we sought to explain these responses. We measured component fluxes, including biomass production, SOC accumulation, and respiration, and summed them into carbon budgets. We compared the resulting summations to ecosystem fluxes measured by eddy covariance. N fertilization increased most component fluxes (P < 0.05), especially SOC accumulation (20×). Only fine-root, mycorrhiza, and exudate production decreased, by 237 (SD = 28) g C m-2 yr-1 . Stemwood production increases were ascribed to this partitioning shift, gross primary production (GPP), and carbon-use efficiency, in that order. The methods agreed in their estimates of GPP in both stands (P > 0.05), but the components detected an increase in net ecosystem production (NEP) (190 (54) g C m-2 yr-1 ; P < 0.01) that eddy covariance did not (19 (62) g C m-2 yr-1 ; ns). The pairing of plots, the simplicity of the sites, and the strength of response provide a compelling description of N effects on the C budget. However, the disagreement between methods calls for further paired tests of N fertilization effects in simple forest ecosystems.

Contrasting warming responses of photosynthesis in early- and late-successional tropical trees.

The productivity and climate feedbacks of tropical forests depend on tree physiological responses to warmer and, over large areas, seasonally drier conditions. However, knowledge regarding such responses is limited due to data scarcity. We studied the impact of growth temperature on net photosynthesis (An), maximum rates of Rubisco carboxylation at 25 °C (Vcmax25), stomatal conductance (gs) and the slope parameter of the stomatal conductance-photosynthesis model (g1), in 10 early successional (ES) and 8 late-successional (LS) tropical tree species grown at three sites along an elevation gradient in Rwanda, differing by 6.8 °C in daytime ambient air temperature. The effect of seasonal drought on An was also investigated. We found that warm climate decreased wet-season An in LS species, but not in ES species. Values of Vcmax25 were lower at the warmest site across both successional groups, and An and Vcmax25 were higher in ES compared with LS species. Stomatal conductance exhibited no significant site differences and g1 was similar across both sites and successional groups. Drought strongly reduced An at warmer sites but not at the coolest montane site and this response was similar in both ES and LS species. Our results suggest that warming has negative effects on leaf-level photosynthesis in LS species, while both LS and ES species suffer photosynthesis declines in a warmer climate with more pronounced droughts. The contrasting responses of An between successional groups may lead to shifts in species' competitive balance in a warmer world, to the disadvantage of LS trees.

Accumulation of antimony and lead in leaves and needles of trees: The role of traffic emissions.

Antimony (Sb) is a toxic metalloid, which has been increasingly used in the brake lining of vehicles, and increased concentrations have been found in soils near abundant traffic. However, since very few investigations of Sb accumulation in urban vegetation have been undertaken there exists a knowledge gap. We studied the concentrations of Sb in leaves and needles of trees in the Gothenburg City area, Sweden. In addition, lead (Pb), also associated with traffic, was investigated. Sb and Pb concentrations of Quercus palustris leaves at seven sites with contrasting traffic intensity varied substantially, correlated with the traffic-related PAH (polycyclic aromatic hydrocarbon) air pollution at the sites and increased during the growing season. Sb but not Pb concentrations were significantly higher in needles of Picea abies and Pinus sylvestris near major roads compared to sites at larger distances. In Pinus nigra needles at two urban streets both Sb and Pb were higher compared to an urban nature park environment, emphasising the role of traffic emissions for these elements. A continued accumulation of Sb and Pb in three years old needles of Pinus nigra, two years old needles of Pinus sylvestris and eleven years old needles of Picea abies was observed. Our data suggest a pronounced link between traffic pollution and Sb accumulation in leaves and needles, where the particles carrying Sb seem not to be transported very far from the source. We also conclude that there exists a strong potential for Sb and Pb bioaccumulation over time in leaves and needles. Implications of these findings are that increased concentrations of toxic Sb and Pb are likely to prevail in environments with high traffic intensity and that Sb can enter the ecological food chain by accumulation in leaves and needles, which is important for the biogeochemical cycling.

Optimal stomatal theory predicts CO2 responses of stomatal conductance in both gymnosperm and angiosperm trees.

Optimal stomatal theory predicts that stomata operate to maximise photosynthesis (Anet ) and minimise transpirational water loss to achieve optimal intrinsic water-use efficiency (iWUE). We tested whether this theory can predict stomatal responses to elevated atmospheric CO2 (eCO2 ), and whether it can capture differences in responsiveness among woody plant functional types (PFTs). We conducted a meta-analysis of tree studies of the effect of eCO2 on iWUE and its components Anet and stomatal conductance (gs ). We compared three PFTs, using the unified stomatal optimisation (USO) model to account for confounding effects of leaf-air vapour pressure difference (D). We expected smaller gs , but greater Anet , responses to eCO2 in gymnosperms compared with angiosperm PFTs. We found that iWUE increased in proportion to increasing eCO2 in all PFTs, and that increases in Anet had stronger effects than reductions in gs . The USO model correctly captured stomatal behaviour with eCO2 across most datasets. The chief difference among PFTs was a lower stomatal slope parameter (g1 ) for the gymnosperm, compared with angiosperm, species. Land surface models can use the USO model to describe stomatal behaviour under changing atmospheric CO2 conditions.

Long term outcome after toxic nodular goitre.

BACKGROUND: The purpose of treating toxic nodular goitre (TNG) is to reverse hyperthyroidism, prevent recurrent disease, relieve symptoms and preserve thyroid function. Treatment efficacies and long-term outcomes of antithyroid drugs (ATD), radioactive iodine (RAI) or surgery vary in the literature. Symptoms often persist for a long time following euthyroidism, and previous studies have demonstrated long-term cognitive and quality of life (QoL) impairments. We report the outcome of treatment, rate of cure (euthyroidism and hypothyroidism), and QoL in an unselected TNG cohort. METHODS: TNG patients (n = 638) de novo diagnosed between 2003-2005 were invited to engage in a 6-10-year follow-up study. 237 patients responded to questionnaires about therapies, demographics, comorbidities, and quality of life (ThyPRO). Patients received ATD, RAI, or surgery according clinical guidelines. RESULTS: The fraction of patients cured with one RAI treatment was 89%, and 93% in patients treated with surgery. The rate of levothyroxine supplementation for RAI and surgery, at the end of the study period, was 58% respectively 64%. Approximately 5% of the patients needed three or more RAI treatments to be cured. The patients had worse thyroid-related QoL scores, in a broad spectrum, than the general population. CONCLUSION: One advantage of treating TNG with RAI over surgery might be lost due to the seemingly similar incidence of hypothyroidism. The need for up to five treatments is rarely described and indicates that the treatment of TNG can be more complex than expected. This circumstance and the long-term QoL impairments are reminders of the chronic nature of hyperthyroidism from TNG.

Heterogeneity of Small Intestinal Neuroendocrine Tumors Metastasis: Biologic Patterns of a Series with Virchow's Node Involvement.

Small intestinal neuroendocrine tumors (SI-NETs) may rarely metastasize to the left supraclavicular lymph nodes, also known as Virchow's node metastasis (VM). Data on prevalence, prognostic significance, and clinical course of disease for SI-NET patients with VM is limited. In this retrospective analysis of 230 SI-NET patients treated at two tertiary referral centers, we found nine patients with VM (prevalence 3.9%). Among those, there were 5 females and median age at SI-NET and VM diagnosis was 61 and 65 years, respectively. Two patients had G1 tumors and five G2, while two tumors were of unspecified grade (median Ki67: 7%, range 2-15%). Four patients presented with synchronous VM, whereas five developed metachronous VM after a median of twenty-four months (range: 4.8-117.6 months). Hepatic metastases were present in seven patients, extrahepatic metastases (EM) in eight (six para-aortic distant lymph node metastases, one lung and one pancreatic metastasis), whereas peritoneal carcinomatosis (PC) in two patients. We used a control group of 18 age- and sex-matched SI-NET patients from the same cohort with stage IV disease but no extra-abdominal metastases. There was no difference in best-recorded response to first line treatment according to RECIST 1.1 as well as progression-free survival (PFS) between patients with VM and those in the control group (Chi-square test p = 0.516; PFS 71.7 vs. 106.9 months [95% CI 38.1-175.8]; log-rank p = 0.855). In addition, median overall survival (OS) of SI-NET patients with VM did not differ from those in the control group (138.6 [95% CI 17.2-260] vs. 109.9 [95% CI 91.7-128] months; log-rank p = 0.533). In conclusion, VM, although relatively rare in patients with SI-NETs, is more often encountered in patients with G2 tumors and established distant para-aortic lymph node metastases. The presence of VM in SI-NET patients does not seem to impact patients' survival outcomes and treatment responses, when compared to age- and sex-matched SI-NET patients with stage IV disease confined in the abdomen.

Temperature acclimation of net photosynthesis and its underlying component processes in four tropical tree species.

The effect of temperature change on leaf physiology has been extensively studied in temperate trees and to some extent in boreal and tropical tree species. While increased temperature typically stimulates leaf CO2 assimilation and tree growth in high-altitude ecosystems, tropical species are often negatively affected. These trees may operate close to their temperature optima and have a limited thermal acclimation capacity due to low seasonal and historical variation in temperature. To test this hypothesis, we studied the extent to which the temperature sensitivities of leaf photosynthesis and respiration acclimate to growth temperature in four common African tropical tree species. Tree seedlings native to different altitudes and therefore adapted to different growth temperatures were cultivated at three different temperatures in climate-controlled chambers. We estimated the acclimation capacity of the temperature sensitivities of light-saturated net photosynthesis, the maximum rates of Rubisco carboxylation (Vcmax) and thylakoid electron transport (J), and dark respiration. Leaf thylakoid membrane lipid composition, nitrogen content and leaf mass per area were also analyzed. Our results showed that photosynthesis in tropical tree species acclimated to higher growth temperatures, but that this was weakest in the species originating from the coolest climate. The temperature optimum of J acclimated significantly in three species and variation in J was linked to changes in the thylakoid membrane lipid composition. For Vcmax, there was only evidence of significant acclimation of optimal temperature in the lowest elevation species. Respiration acclimated to maintain homeostasis at growth temperature in all four species. Our results suggest that the lowest elevation species is better physiologically adapted to acclimate to high growth temperatures than the highest elevation species, indicating a potential shift in competitive balance and tree community composition to the disadvantage of montane tree species in a warmer world.

Limits to photosynthesis: seasonal shifts in supply and demand for CO2 in Scots pine.

Boreal forests undergo a strong seasonal photosynthetic cycle; however, the underlying processes remain incompletely characterized. Here, we present a novel analysis of the seasonal diffusional and biochemical limits to photosynthesis (Anet ) relative to temperature and light limitations in high-latitude mature Pinus sylvestris, including a high-resolution analysis of the seasonality of mesophyll conductance (gm ) and its effect on the estimation of carboxylation capacity ( VCmax ). We used a custom-built gas-exchange system coupled to a carbon isotope analyser to obtain continuous measurements for the estimation of the relevant shoot gas-exchange parameters and quantified the biochemical and diffusional controls alongside the environmental controls over Anet . The seasonality of Anet was strongly dependent on VCmax and the diffusional limitations. Stomatal limitation was low in spring and autumn but increased to 31% in June. By contrast, mesophyll limitation was nearly constant (19%). We found that VCmax limited Anet in the spring, whereas daily temperatures and the gradual reduction of light availability limited Anet in the autumn, despite relatively high VCmax . We describe for the first time the role of mesophyll conductance in connection with seasonal trends in net photosynthesis of P. sylvestris, revealing a strong coordination between gm and Anet , but not between gm and stomatal conductance.

Handling the heat - photosynthetic thermal stress in tropical trees.

Warming climate increases the risk for harmful leaf temperatures in terrestrial plants, causing heat stress and loss of productivity. The heat sensitivity may be particularly high in equatorial tropical tree species adapted to a thermally stable climate. Thermal thresholds of the photosynthetic system of sun-exposed leaves were investigated in three tropical montane tree species native to Rwanda with different growth and water use strategies (Harungana montana, Syzygium guineense and Entandrophragma exselsum). Measurements of chlorophyll fluorescence, leaf gas exchange, morphology, chemistry and temperature were made at three common gardens along an elevation/temperature gradient. Heat tolerance acclimated to maximum leaf temperature (Tleaf ) across the species. At the warmest sites, the thermal threshold for normal function of photosystem II was exceeded in the species with the highest Tleaf despite their higher heat tolerance. This was not the case in the species with the highest transpiration rates and lowest Tleaf . The results point to two differently effective strategies for managing thermal stress: tolerance through physiological adjustment of leaf osmolality and thylakoid membrane lipid composition, or avoidance through morphological adaptation and transpiratory cooling. More severe photosynthetic heat stress in low-transpiring montane climax species may result in a competitive disadvantage compared to high-transpiring pioneer species with more efficient leaf cooling.

Polycyclic aromatic hydrocarbon (PAH) accumulation in Quercus palustris and Pinus nigra in the urban landscape of Gothenburg, Sweden.

Trees have the potential to improve urban air quality as leaves and needles capture air pollutants from the air, but further empirical data has been requested to quantify these effects. We measured the concentration of 32 polycyclic aromatic hydrocarbons (PAHs) in leaves of pin oak (Quercus palustris) and needles of black pine (Pinus nigra) in the City of Gothenburg, Sweden, during the summer of 2018. Oak leaves were collected twice (June, September), while one-year-old (C + 1) and three-year-old (C + 3) pine needles were sampled in June to study the temporal development of leaf/needle PAH concentrations. Specific leaf area (SLA) was estimated, which permitted calculation of leaf/needle area-based PAH content that were compared with the mass-based concentration. In addition, the air concentration of PAHs and NO2 was measured using passive samplers. There was a strong correlation between air concentrations of PAH and NO2, indicating that the pollutants to a large degree originate from the same sources. In the oak leaves there was a significant decrease in low molecular mass PAHs (L-PAH, mainly gaseous) between June and September, but a significant increase in high molecular mass PAHs (H-PAH, mainly particle-bound). There was a strong correlation between L-PAH concentration in leaves and in air indicating an influence of equilibrium processes between ambient air and leaf. In the pine needles, there was a significant increase of both L-PAH and H-PAH in three-year-old needles compared to one-year-old needles. Pine was superior to oak in accumulating PAHs from the air, especially for L-PAHs when comparing area-based content. However, H-PAH concentrations were higher in oak leaves compared to pine needles on a leaf mass basis, emphasizing the importance of how concentrations are expressed. The results from this study can contribute to the development of urban planning strategies regarding the effect of vegetation on air quality.

Treatment of patients with Graves' disease in Sweden compared to international surveys of an 'index patient'.

INTRODUCTION: The treatment strategies for a 42-year-old female index patient with moderate Graves' disease (GD) vary according to several international surveys. The important question whether surveys of treatment preferences in theoretical patient cases also match how real patients are treated has not yet been addressed. MATERIALS AND METHODS: From a Swedish cohort of 1186 GD patients (TT-12 cohort), 27 women were identified using the same criteria as from the index patient surveys from the European and American Thyroid Associations. This 'index patient cohort' was age 40-45, otherwise healthy female, with two children and uncomplicated GD. The applied first-line treatment of the patients in the index cohort, together with its variations, was compared with the treatment preferences according to international surveys. A comparison with the TT-12 cohort was also performed. RESULTS: In the 'Index cohort', 77.8% were treated with antithyroid drugs (ATD), and 22.2% were treated with radioiodine (131I). This preference for ATD is in line with most countries/regions, with the exception of USA and the Middle East/North Africa, where 131I was preferred. The distribution of treatment in the TT-12 cohort did not significantly differ from the index cohort. ATD was the preferred treatment in male and young (age 19-22) patients, as was RAI in old (age 69-73) patients. The age-related, but not the gender-related, cases differed significantly from the entire TT-12 cohort. CONCLUSION: The treatment choice in an index patient in Sweden seems in line with European practice, where ATD is the preferred first choice. This differs compared to US and North African survey intentions, where 131I is more often used. Age more than gender influences the treatment choice of GD patients. This is, to our best knowledge, the first time an index patient from 'real life' has been presented and compared to treatment preferences of international thyroid association surveys.

Limited thermal acclimation of photosynthesis in tropical montane tree species.

The temperature sensitivity of physiological processes and growth of tropical trees remains a key uncertainty in predicting how tropical forests will adjust to future climates. In particular, our knowledge regarding warming responses of photosynthesis, and its underlying biochemical mechanisms, is very limited. We grew seedlings of two tropical montane rainforest tree species, the early-successional species Harungana montana and the late-successional species Syzygium guineense, at three different sites along an elevation gradient, differing by 6.8℃ in daytime ambient air temperature. Their physiological and growth performance was investigated at each site. The optimum temperature of net photosynthesis (ToptA ) did not significantly increase in warm-grown trees in either species. Similarly, the thermal optima (ToptV and ToptJ ) and activation energies (EaV and EaJ ) of maximum Rubisco carboxylation capacity (Vcmax ) and maximum electron transport rate (Jmax ) were largely unaffected by warming. However, Vcmax , Jmax and foliar dark respiration (Rd ) at 25℃ were significantly reduced by warming in both species, and this decline was partly associated with concomitant reduction in total leaf nitrogen content. The ratio of Jmax /Vcmax decreased with increasing leaf temperature for both species, but the ratio at 25℃ was constant across sites. Furthermore, in H. montana, stomatal conductance at 25℃ remained constant across the different temperature treatments, while in S. guineense it increased with warming. Total dry biomass increased with warming in H. montana but remained constant in S. guineense. The biomass allocated to roots, stem and leaves was not affected by warming in H. montana, whereas the biomass allocated to roots significantly increased in S. guineense. Overall, our findings show that in these two tropical montane rainforest tree species, the capacity to acclimate the thermal optimum of photosynthesis is limited while warming-induced reductions in respiration and photosynthetic capacity rates are tightly coupled and linked to responses of leaf nitrogen.