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The International Prognostic Index (IPI) is the most frequently used tool for prognostication in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) of all ages. This study validated and compared six models developed for patients above 60 with International Prognostic Indices (IPI, R-IPI, NCCN-IPI). Moreover, we created a clinical nomogram with an online tool for individualized predictions. A total of 2,835 patients aged over 60 with newly diagnosed DLBCL treated with potentially curative immunochemotherapy were identified in the Danish Lymphoma Registry. A nomogram was developed by combining NCCN-IPI variables (excluding extranodal localization), albumin, and platelet levels in 1,970 patients and verified the results in the remaining 956 patients. Compared to other models, the elderly IPI (E-IPI) and age-adjusted IPI (aaIPI) showed better accuracy and discriminatory ability. However, the models failed to identify a high-risk group with a 3-year overall survival rate below 40%. Our nomogram-based model demonstrated superior discriminatory ability and provided more precise individual predictions than all other models based on a risk stratification system. Most clinical prognostic models fail to accurately predict patient outcomes in patients over 60 years old. Therefore, nomogram-based models should be considered in this population to prevent information loss due to variable dichotomization., Competing Interests: Declarations. Competing interests: JJ has received travel support from AstraZeneca and Roche. PB has served on advisory boards for Roche, Abbvie, and SERB. TSL has served on advisory boards/consultancy for Roche, Novartis, Gilead, and BMS. TSL received a research Grant from Genentech and travel support from Roche. Other authors have no relevant financial or non-financial interests to disclose. Ethical approval and consent to participate: This study was performed in accordance with the principles of the Declaration of Helsinki. The Advisory Board for Clinical Quality Development Program (RKKP) (project number 21/27006) has granted approval for conducting this registry-based study, ensuring total anonymity of patients. Further details can be found in the Declaration on passing personal data covered by § 10, a subsection of the Data Protection Act, 1 and 2’, https://www.retsinformation.dk/eli/lta/2019/1509 . Therefore, informed consent from patients was not obtained., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Recent front-line clinical trials used the International Prognostic Index (IPI) to identify trial-eligible patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). However, many IPI-like variants with improved accuracy have been developed over the years for rituximab-treated patients., Methods: We assessed the impact of International Prognostic Indices on patient enrolment in clinical trials, aiming to exclude low-risk IPI patients based on POLARIX/EPCORE DLBCL-2 trial criteria., Results: We identified 2877 patients in the Danish Lymphoma Registry who would have been eligible for the POLARIX trial if patients with IPI 0-1 scores were included. IPI and NCCN-IPI assigned 33.3% and 11.9% of patients to the low-risk group, respectively. Shorter 5-year overall survival (91.4% vs. 97.5%), higher relapse rate (9.9% vs. 4.4%), and more deaths (16.1% vs. 4.4%) occurred in the low-risk IPI group compared with low-risk NCCN-IPI group. Analyzed models failed to identify true high-risk patients with poor prognosis. Similar results were found in the confirmatory cohort developed based on EPCORE DLBCL-2 trial eligibility criteria., Conclusion: True low-risk patients are more optimal identified by NCCN-IPI and should be excluded from front-line clinical trials due to their excellent prognosis. However, additional high-risk factors besides clinical prognostic models need to be considered when selecting trial-eligible patients., (© 2024 The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.)

Background: Several clinical prognostic models for diffuse large B-cell lymphoma (DLBCL) have been proposed, including the most commonly used International Prognostic Index (IPI), the National Comprehensive Cancer Network IPI (NCCN-IPI), and models incorporating beta-2 microglobulin (β2M). However, the role of β2M in DLBCL patients is not fully understood., Methods: We identified 6075 patients with newly diagnosed DLBCL treated with immunochemotherapy registered in the Danish Lymphoma Registry., Results: A total of 3232 patients had data available to calculate risk scores from each of the nine considered risk models for DLBCL, including a model developed from our population. Three of four models with β2M and NCCN-IPI performed better than the International Prognostic Indexes (IPI, age-adjusted IPI, and revised IPI). Five-year overall survival for high- and low-risk patients were 43.6% and 86.4% for IPI and 34.9% and 96.2% for NCCN-IPI. In univariate analysis, higher levels of β2M were associated with inferior survival, higher tumor burden (advanced clinical stage and bulky disease), previous malignancy and increased age, and creatinine levels. Furthermore, we developed a model (β2M-NCCN-IPI) by adding β2M to NCCN-IPI (c-index 0.708) with improved discriminatory ability compared to NCCN-IPI (c-index 0.698, p < 0.05) and 5-year OS of 33.1%, 56.2%, 82.4%, and 96.4% in the high, high-intermediate, low-intermediate and low-risk group, respectively., Conclusion: International Prognostic Indices, except for NCCN-IPI, fail to accurately discriminate risk groups in the rituximab era. β2M, a readily available marker, could improve the discriminatory performance of NCCN-IPI and should be re-evaluated in the development setting of future models for DLBCL., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Currently, the International Prognostic Index (IPI) is the most used and reported model for prognostication in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). IPI-like variations have been proposed, but only a few have been validated in different populations (e.g., revised IPI (R-IPI), National Comprehensive Cancer Network IPI (NCCN-IPI)). We aimed to validate and compare different IPI-like variations to identify the model with the highest predictive accuracy for survival in newly diagnosed DLBCL patients. We included 5126 DLBCL patients treated with immunochemotherapy with available data required by 13 different prognostic models. All models could predict survival, but NCCN-IPI consistently provided high levels of accuracy. Moreover, we found similar 5-year overall survivals in the high-risk group (33.4%) compared to the original validation study of NCCN-IPI. Additionally, only one model incorporating albumin performed similarly well but did not outperform NCCN-IPI regarding discrimination (c-index 0.693). Poor fit, discrimination, and calibration were observed in models with only three risk groups and without age as a risk factor. In this extensive retrospective registry-based study comparing 13 prognostic models, we suggest that NCCN-IPI should be reported as the reference model along with IPI in newly diagnosed DLBCL patients until more accurate validated prognostic models for DLBCL become available., (© 2023. Springer Nature Limited.)

Peripheral T-Cell Lymphomas (PTCLs) are rare, aggressive lymphomas with poor outcomes, but limited-stage disease is infrequent and not well-described. This study reports outcomes and prognostic factors in limited-stage nodal PTCLs in a binational population-based setting. Patients were identified from the Danish and Swedish lymphoma registries. Adults diagnosed with limited-stage nodal PTCL (stage I-II) and treated with CHOP(-like) therapy ±radiotherapy between 2000 and 2014 were included. Medical records were reviewed by local investigators. A total of 239 patients with a median age of 62 years were included; 67% received 6-8 cycles of CHOP(-like) therapy and 22% received 3-4 cycles, of which 59% also received radiotherapy. Autologous stem cell transplant consolidation was administered to 16% of all patients. Median follow-up was 127 months with 5-years overall survival (OS) of 58% (95% CI: 53-65) and progression-free survival (PFS) of 53% (95% CI: 47-59). In multivariable analysis, age ≥ 60 years and B-symptoms were unfavorable and ALK+ anaplastic large cell T-Cell lymphoma was favorable for survival outcomes. There was no difference in treatment-specific outcome (3-4 cycles vs. 6-8 cycles of CHOP(-like) ± radiotherapy). Low-risk patients (age < 60 without B-symptoms) had a 5-year OS of 77% (95% CI 67-89%). In the present study of limited-stage nodal PTCL, survival after curative intent chemotherapy +/- radiotherapy was inferior to that of limited-stage diffuse large B-cell lymphoma, but a subgroup of young patients without B-symptoms had very good outcomes. Treatment outcomes after 3-4 cycles versus 6-8 cycles of CHOP(-like) therapy were comparable., (© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Introduction: One of the challenges of surgery on patients with active SARS-CoV-2(severe acute respiratory syndrome coronavirus 2) infection is the increased risk of postoperative morbidity and mortality., Aim: This study will describe and compare the postoperative morbidity and mortality in asymptomatic patients or those with mild infection with those with severe COVID-19 infection undergoing elective or and emergency surgery., Materials and Methods: This is a retrospective study of 37 COVID 19 patients who had the infection 7 days prior to and 30 days after emergency or elective surgery. Patients were divided to two groups. Group1: the asymptomatic or those with mild infection that is diagnosed just before surgery (14 patients). Group 2: those who were admitted to the hospital because of severe COVID-19 and were operated for COVID-19 related complications (23 patients). Morbidity and mortality of both groups was studied., Results: There was no significant difference in gender between the two groups. There were 5 females (2 in group 1, and 3 in group 2) and 32 males (12 in group 1, and 20 in group 2). Mean age for all patients was 49.8years (38 for group 1 and 57 for group2). Median age for all patients was 50 years (37.5 for group 1 and 57 years for group 2). Sepsis developed in 7 patients (1 patient in group 1 and in 6 patients in group 2). Statistically there was no significant difference in occurrence of sepsis between the two groups. There was a significant difference in the intensive care stay between the two groups (higher in group 2). Four deaths were reported in group 1 and fourteen in group 2. Eighteen out of thirty-seven patients died., Conclusion: Severity of COVID-19 infection will prolong the hospitalization and ICU stay in surgical patients with no significant effect on mortality., Competing Interests: Authors declare that they have no conflicts of interest to disclose., (© 2022 The Authors.)

Psychological distress following cancer diagnosis may lead to mental health complications including depression and anxiety. Non-Hodgkin lymphomas (NHLs) include indolent and aggressive subtypes for which treatment and prognosis differ widely. Incident use of psychotropic drugs (PDs-antidepressants, antipsychotics, and anxiolytics) and its correlation to lymphoma types can give insights into the psychological distress these patients endure. In this prospective matched cohort study, we used nationwide population-based registries to investigate the cumulative risk of PD use in NHL patients compared to a sex- and age-matched cohort from the Danish background population. In addition, contact patterns to psychiatric departments and incident intentional self-harm or completed suicide were explored. In total, 8750 NHL patients and 43 750 matched comparators were included (median age 68; male:female ratio 1.6). Median follow-up was 7.1 years. Two-year cumulative risk of PD use was higher in NHL patients (16.4%) as compared to the matched comparators (5.1%, p < .01); patients with aggressive NHL subtypes had the highest incidence. Prescription rates were higher in the first years after diagnosis but approached the rate of the matched population 5 years into survivorship in aggressive NHLs, whereas patients with indolent subtypes continued to be at higher risk. NHL patients had a slightly higher two-year risk of suicide/intentional self-harm (0.3%) as compared to the matched comparators (0.2%, p = .01). These results demonstrate that mental health complications among NHL patients are frequent. Routine assessment for symptoms of depression and anxiety should be consider as part of standard follow-up of NHL patients., (© 2022 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Background/purpose: The aims of this study were to evaluate bowel and urinary tract function, to identify predictors for dysfunctional outcome and to evaluate health-related quality-of life (QoL) in patients treated for sacrococcygeal teratomas (SCT)., Methods: Medical records of patients with SCT born between 1985 and 2015 treated at three Swedish pediatric surgical centers were reviewed. Questionnaires regarding urinary tract function, bowel function and QoL were sent to patients and parents. Different QoL instruments were used for the different age groups., Results: Totally 85 patients were identified. Four patients died in the neonatal period. Forty-nine patients answered the questionnaires (60%). Median age at follow-up was 8.9 years (range 3.6-28.8). Bowel dysfunction was reported by 36% and urinary tract dysfunction by 46% of the patients. Univariate analysis revealed that urinary tract dysfunction correlated with gestational age (p = 0.018) and immature histology (p = 0.008), and bowel dysfunction correlated with gestational age (p = 0.016) and tumor size (p = 0.042). Low gestational age was an independent predictor for both urinary tract and bowel dysfunction. Good or very good QoL was reported by 56% of children aged 4-7 years, 90% of children aged 8-17 years and 67% of the adults., Conclusion: Although a considerable proportion of bowel and urinary tract dysfunction was found, the reported QoL was good in a majority of the patients with SCT. Low gestational age was found to be a predictor for bowel- and urinary tract dysfunction., Level of Evidence: Level III., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: As much as 20% of all cases of hypertension are associated with kidney malfunctions. We have previously demonstrated in animals and in pediatric patients that hydronephrosis causes hypertension, which was attenuated by surgical relief of the ureteropelvic junction (UPJ) obstruction. This retrospective cohort study aimed to investigate: (1) the proposed link between hydronephrosis, due to UPJ obstruction, and elevated arterial pressure in adults; and (2) if elevated blood pressure in patients with hydronephrosis might be another indication for surgery., Materials and Methods: Medical records of 212 patients undergoing surgical management of hydronephrosis, due to UPJ obstruction, between 2000 and 2016 were assessed. After excluding patients with confounding conditions and treatments, paired arterial pressures (i.e. before/after surgery) were compared in 49 patients (35 years old; 95% CI 29-39). Split renal function was evaluated by using mercaptoacetyltriglycine (MAG3) renography before surgical management of the hydronephrotic kidney., Results: Systolic (-11 mmHg; 95% CI 6-15 mmHg), diastolic (-8 mmHg; 95% CI 4-11 mmHg), and mean arterial (-9 mmHg; 95% CI 6-12) pressures were significantly reduced after relief of the obstruction (p < 0.001). Split renal function of the hydronephrotic kidney was 39% (95% CI 37-41). No correlations were found between MAG3 and blood pressure level before surgery or between MAG3 and the reduction of blood pressure after surgical management of the UPJ obstruction., Conclusions: In adults with hydronephrosis, blood pressure was reduced following relief of the obstruction. Our findings suggest that elevated arterial pressure should be taken into account as an indication to surgically correct hydronephrosis.

Obstruction of urine flow at the level of the pelvo-ureteric junction (UPJO) and subsequent development of hydronephrosis is one of the most common congenital renal malformations. UPJO is associated with development of salt-sensitive hypertension, which is set by the obstructed kidney, and with a stimulated renin-angiotensin-aldosterone system (RAAS) in rodent models. This study aimed at investigating the hypothesis that 1) in pediatric patients with UPJO the RAAS is activated before surgical relief of the obstruction; 2) in rats with UPJO the RAAS activation is reflected by increased abundance of renal aldosterone-stimulated Na transporters; and 3) the injured UPJO kidney allows aberrant filtration of plasminogen, leading to proteolytic activation of the epithelial Na channel γ-subunit (γ-ENaC). Hydronephrosis resulting from UPJO in pediatric patients and rats was associated with increased urinary plasminogen-to-creatinine ratio. In pediatric patients, plasma renin, angiotensin II, urine and plasma aldosterone, and urine soluble prorenin receptor did not differ significantly before or after surgery, or compared with controls. Increased plasmin-to-plasminogen ratio was seen in UPJO rats. Intact γ-ENaC abundance was not changed in UPJO kidney, whereas low-molecular cleavage product abundance increased. The Na-Cl cotransporter displayed significantly lower abundance in the UPJO kidney compared with the nonobstructed contralateral kidney. The Na-K-ATPase α-subunit was unaltered. Treatment with an angiotensin-converting enzyme inhibitor (8 days, captopril) significantly lowered blood pressure in UPJO rats. It is concluded that the RAAS contributes to hypertension following partial obstruction of urine flow at the pelvo-ureteric junction with potential contribution from proteolytic activation of ENaC.

Objective: Recent clinical studies have suggested an increased risk of elevated arterial pressure in patients with hydronephrosis. Animals with experimentally induced hydronephrosis develop hypertension, which is correlated to the degree of obstruction and increased oxidative stress. In this prospective study we investigated changes in arterial pressure, oxidative stress, and nitric oxide (NO) homeostasis following correction of hydronephrosis., Methods: Ambulatory arterial pressure (24 h) was monitored in pediatric patients with hydronephrosis (n = 15) before and after surgical correction, and the measurements were compared with arterial pressure measurements in two control groups, i.e. healthy controls (n = 8) and operated controls (n = 8). Markers of oxidative stress and NO homeostasis were analyzed in matched urine and plasma samples., Results: The preoperative mean arterial pressure was significantly higher in hydronephrotic patients [83 mmHg; 95% confidence interval (CI) 80-88 mmHg] than in healthy controls (74 mmHg; 95% CI 68-80 mmHg; p < 0.05), and surgical correction of ureteral obstruction reduced arterial pressure (76 mmHg; 95% CI 74-79 mmHg; p < 0.05). Markers of oxidative stress (i.e., 11-dehydroTXB 2 , PGF 2α , 8-iso-PGF 2α , 8,12-iso-iPF 2α -VI) were significantly increased (p < 0.05) in patients with hydronephrosis compared with both control groups, and these were reduced following surgery (p < 0.05). Interestingly, there was a trend for increased NO synthase activity and signaling in hydronephrosis, which may indicate compensatory mechanism(s)., Conclusion: This study demonstrates increased arterial pressure and oxidative stress in children with hydronephrosis compared with healthy controls, which can be restored to normal levels by surgical correction of the obstruction. Once reference data on ambulatory blood pressure in this young age group become available, we hope cut-off values can be defined for deciding whether or not to correct hydronephrosis surgically.

Hydronephrosis is associated with the development of salt-sensitive hypertension. Studies have suggested that increased sympathetic nerve activity and oxidative stress play important roles in hypertension and the modulation of salt sensitivity. The present study primarily aimed to examine the role of renal sympathetic nerve activity in the development of hypertension in rats with hydronephrosis. In addition, we aimed to investigate if NADPH oxidase (NOX) function could be affected by renal denervation. Partial unilateral ureteral obstruction (PUUO) was created in 3-wk-old rats to induce hydronephrosis. Sham surgery or renal denervation was performed at the same time. Blood pressure was measured during normal, high-, and low-salt diets. The renal excretion pattern, NOX activity, and expression as well as components of the renin-angiotensin-aldosterone system were characterized after treatment with the normal salt diet. On the normal salt diet, rats in the PUUO group had elevated blood pressure compared with control rats (115 ± 3 vs. 87 ± 1 mmHg, P < 0.05) and displayed increased urine production and lower urine osmolality. The blood pressure change in response to salt loading (salt sensitivity) was more pronounced in the PUUO group compared with the control group (15 ± 2 vs. 5 ± 1 mmHg, P < 0.05). Renal denervation in PUUO rats attenuated both hypertension (97 ± 3 mmHg) and salt sensitivity (5 ± 1 mmHg, P < 0.05) and normalized the renal excretion pattern, whereas the degree of renal fibrosis and inflammation was not changed. NOX activity and expression as well as renin and ANG II type 1A receptor expression were increased in the renal cortex from PUUO rats and normalized by denervation. Plasma Na(+) and K(+) levels were elevated in PUUO rats and normalized after renal denervation. Finally, denervation in PUUO rats was also associated with reduced NOX expression, superoxide production, and fibrosis in the heart. In conclusion, renal denervation attenuates hypertension and restores the renal excretion pattern, which is associated with reduced renal NOX and components of the renin-angiotensin-aldosterone system. This study emphasizes a link between renal nerves, the development of hypertension, and modulation of NOX function., (Copyright © 2016 the American Physiological Society.)

Objective: Renal disorders can cause hypertension, but less is known about the influence of hydronephrosis on blood pressure. Hydronephrosis due to pelvo-ureteric junction obstruction (PUJO) is a fairly common condition (incidence in newborns of 0.5-1%). Although hypertensive effects of hydronephrosis have been suggested, this has not been substantiated by prospective studies in humans [1-3]. Experimental studies with PUJO have shown that animals with induced hydronephrosis develop salt-sensitive hypertension, which strongly correlate to the degree of obstruction [4-7]. Moreover, relief of the obstruction normalized blood pressure [8]. In this first prospective study our aim was to study the blood pressure pattern in pediatric patients with hydronephrosis before and after surgical correction of the ureteral obstruction. Specifically, we investigated if preoperative blood pressure is reduced after surgery and if split renal function and renographic excretion curves provide any prognostic information., Patients and Methods: Twelve patients with unilateral congenital hydronephrosis were included in this prospective study. Ambulatory blood pressure (24 h) was measured preoperatively and six months after surgery. Preoperative evaluations of bilateral renal function by Tc99m-MAG3 scintigraphy, and renography curves, classified according to O'Reilly, were also performed., Results: As shown in the summary figure, postoperative systolic (103 ± 2 mmHg) and diastolic (62 ± 2 mmHg) blood pressure were significantly lower than those obtained preoperatively (110 ± 4 and 69 ± 2 mmHg, respectively), whereas no changes in circadian variation or pulse pressure were observed. Renal functional share of the hydronephrotic kidney ranged from 11 to 55%. There was no correlation between the degree of renal function impairment and the preoperative excretory pattern, or between the preoperative excretory pattern and the blood pressure reduction postoperatively. However, preoperative MAG3 function of the affected kidney correlated with the magnitude of blood pressure change after surgery., Discussion: Correction of the obstruction lowered blood pressure, and the reduction in blood pressure appeared to correlate with the degree of renal functional impairment, but not with the excretory pattern. Thus, in the setting of hypertension, it appears that the functional share of the hydronephrotic kidney should be considered an indicator of the need for surgery, whereas the renography curve is less reliable. The strength of the present study is the prospective nature and that ambulatory blood pressure monitoring was used. Future longitudinal prolonged follow-up studies are warranted to confirm the present findings, and to understand if a real nephrogenic hypertension with potential necessity of treatment will develop., Conclusion: This novel prospective study in patients with congenital hydronephrosis demonstrates a reduction in blood pressure following relief of the obstruction. Based on the present results, we propose that the blood pressure level should also be taken into account when deciding whether to correct hydronephrosis surgically or not., (Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

A study was conducted to evaluate the efficacy of three chemical disinfectants and of ionising radiation in reducing the level of contamination in chicken carcasses which had been artificially contaminated with Salmonella Virchow. Chicken carcasses were obtained from a local abattoir. Five carcasses and one control carcass were used to test each concentration of disinfectant and the radiation. The amount of contaminant employed was 0.5 ml of 10(4) colony-forming units per ml of S. Virchow spread over the thigh, breast and wing areas. All treatments were conducted in duplicate. The three disinfectants used were as follows: calcium hypochlorite, at concentrations of 20 ppm, 50 ppm, 100 ppm and 200 ppm of available chlorine. Lactic acid at concentrations of 0.5%, 0.75% and 1%. Hydrogen peroxide compound at concentrations of 1%, 2% and 3%. Five inoculated carcasses were immersed at a time in one disinfectant concentration for 15 min, while the control carcasses were simultaneously immersed in water free from disinfectants. Five carcasses, each in a plastic bag, were subjected to varying ascending doses (from 2 to 7 k gray [kGy]) of ionising radiation from radioactive isotopes of cobalt 60. A bacteriological examination of each carcass was conducted after the treatment to determine the presence or absence of S. Virchow. The number of carcasses which gave positive results showing the presence of Salmonella decreased after chemical treatment, but the organism was not completely eliminated. However, in those carcasses subjected to 7 kGy of radiation, Salmonella was eliminated and no changes in the appearance, colour or smell of the carcasses were observed.