Assessment of Outcomes by Intention-to-Treat Comparison for Locally Advanced Pancreatic Cancer: A Population-Derived Cohort Study.

BACKGROUND: The overall treatment response among patients with locally advanced pancreatic cancer (LAPC) is poorly understood as most studies report solely on resected patients. We aimed to investigate the outcomes in patients with LAPC as an intention-to-treat-analysis from the time of diagnosis from a complete source population. PATIENTS AND METHODS: An observational cohort study in a population-defined region within a universal healthcare system. All consecutive patients discussed at multi-disciplinary tumour board (MDT), aged ≥ 18 years and diagnosed with LAPC were included. Exposure was set as recommended treatment by MDT (i.e. upfront surgery, neoadjuvant therapy, palliative treatment or best supportive care). Outcome measures were overall survival analysed by Kaplan-Meier survival estimates and multivariable analyses using logistic regression for odds ratios (OR) and Cox proportional hazard analysis for hazard ratios (HR). RESULTS: In total, 8803 MDT events (6055 unique patients) with pancreatic disease were held during the study period. Some 1436 (24%) had pancreatic cancer, of which 162 (11%) had LAPC and 134 met the population-defined criteria. In overall survival analyses, the patients who were recommended neoadjuvant therapy (± surgery) demonstrated no significant difference to palliative chemotherapy (median 11.0 months vs. 11.8 months; p = 0.226). In multivariable analysis, adjusted OR for overall survival comparing the treatment groups was 0.27 (95% CI 0.02-3.29, p = 0.306) and Cox proportional HR 0.96 (95% CI 0.58-1.59, p = 0.865). CONCLUSIONS: In patients with LAPC, survival was not statistically different between those recommended for attempt at neoadjuvant (± surgery) compared with those recommended palliative chemotherapy. The findings suggest that conversion/downstaging chemotherapy is successful in only a select few.

Risk factors for acute kidney injury after pancreatoduodenectomy, and association with postoperative complications and death.

BACKGROUND: Acute kidney injury (AKI) is associated with increased morbidity and mortality after general surgery, although little is known among patients undergoing pancreatoduodenectomy. The objective was to investigate the association between AKI and postoperative complications and death after pancreatoduodenectomy. METHODS: All patients ≥18 years who underwent a pancreatoduodenectomy 2008-2019 at the Karolinska University Hospital, Stockholm, Sweden, were included. Standardized criteria for AKI, including estimated glomerular filtration rate (eGFR) and urine volume measurements, were used to grade postoperative AKI. RESULTS: In total, 970 patients were included with a median age of 68 years (IQR 61-74) of whom 517 (53.3%) were men. There were 137 (14.1%) patients who developed postoperative AKI. Risk factors for AKI included lower preoperative eGFR, cardiovascular disease and treatment with renin-angiotensin system inhibitors or diuretics. Those who developed AKI had a higher risk of severe postoperative complications, including Clavien-Dindo score ≥ IIIa (adjusted OR 3.35, 95% CI 2.24-5.01) and ICU admission (adjusted OR 7.83, 95% CI 4.39-13.99). In time-to-event analysis, AKI was associated with an increased risk for both 30-day mortality (adjusted HR 4.51, 95% CI 1.54-13.27) and 90-day mortality (adjusted HR 4.93, 95% CI 2.37-10.26). Patients with benign histology and AKI also had an increased 1-year mortality (HR 4.89, 95% CI 1.88-12.71). CONCLUSIONS: Postoperative AKI was associated with major postoperative complications and an increased risk of postoperative mortality. Monitoring changes in serum creatinine levels and urine volume output could be important in the immediate perioperative period to improve outcomes after pancreatoduodenectomy.

Sex Differences in the Recognition, Monitoring, and Management of CKD in Health Care: An Observational Cohort Study.

INTRODUCTION: Reported sex differences in the etiology, population prevalence, progression rates, and health outcomes of people with CKD may be explained by differences in health care. METHODS: We evaluated sex as the variable of interest in a health care-based study of adults (n=227,847) with at least one outpatient eGFR<60 ml/min per 1.73 m2 measurement denoting probable CKD in Stockholm from 2009 to 2017. We calculated the odds ratios for diagnosis of CKD and provision of RASi and statins at inclusion, and hazard ratios for CKD diagnosis, visiting a nephrologist, or monitoring creatinine and albuminuria during follow-up. RESULTS: We identified 227,847 subjects, of whom 126,289 were women (55%). At inclusion, women had lower odds of having received a diagnostic code for CKD and were less likely to have received RASi and statins, despite having guideline-recommended indications. In time-to-event analyses, women were less likely to have received a CKD diagnosis (HR, 0.43; 95% CI, 0.42 to 0.45) and visited a nephrologist (HR, 0.46; 95% CI, 0.43 to 0.48) regardless of disease severity, presence of albuminuria, or criteria for referral. Women were also less likely to undergo monitoring of creatinine or albuminuria, including those with diabetes or hypertension. These differences remained after adjustment for comorbidities, albuminuria, and highest educational achievement, and among subjects with confirmed CKD at retesting. Although in absolute terms all nephrology-care indicators gradually improved over time, the observed sex gap persisted. CONCLUSIONS: There were profound sex differences in the detection, recognition, monitoring, referrals, and management of CKD. The disparity was also observed in people at high risk and among those who had guideline-recommended indications. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/JASN/2022_10_11_JASN2022030373.mp3.

Preoperative heart disease and risk for postoperative complications after pancreatoduodenectomy.

BACKGROUND: Comorbidities increase the risk for postoperative complications after pancreatoduodenectomy. The importance of different categories of heart disease on postoperative outcomes has not been thoroughly studied. METHODS: Patients aged ≥18 years undergoing pancreatoduodenectomy between 2008 and 2019 at Karolinska University Hospital, Sweden were included. Heart disease was defined as a preoperatively established diagnosis, and subcategorized into ischaemic, valvular, heart failure and atrial fibrillation. Postoperative outcome was analysed by multivariable regression. RESULTS: Out of 971 patients, 225 (23.3%) had heart disease. Heart disease was associated with an increased risk for complications; Clavien-Dindo score ≥ IIIa (Odds Ratio [OR] 1.53, 95% confidence interval [CI] 1.07-2.18; p = 0.019), intensive care unit admissions (OR 3.20, 95% CI 1.81-5.66; p < 0.001) and longer hospitalizations (median 14 vs. 11 days; p < 0.001). Although heart disease was not associated with 90-day mortality, it conferred a shorter median overall survival (22 vs. 32 months; p < 0.001). Atrial fibrillation and heart failure were each associated with increased risk for postoperative complications, whereas ischaemic and valvular heart disease were not. CONCLUSION: Atrial fibrillation and heart failure were independently associated with increased risk for postoperative complications. Despite no association with early postoperative mortality, heart disease negatively affected long-term survival.

CKD Progression and Mortality Among Men and Women: A Nationwide Study in Sweden.

RATIONALE & OBJECTIVE: Chronic kidney disease (CKD) is a global health problem with increasing prevalence. Several sex-specific differences have been reported for disease progression and mortality. Selection and survival bias might have influenced the results of previous cohort studies. The objective of this study was to investigate sex-specific differences of CKD progression and mortality among patients with CKD not receiving maintenance dialysis. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: Adult patients with incident CKD glomerular filtration rate categories 3b to 5 (G3b-G5) identified between 2010 and 2018 within the nationwide Swedish Renal Registry-CKD (SRR-CKD). EXPOSURE: Sex. OUTCOMES: Time to CKD progression (defined as a change of at least 1 CKD stage or initiation of kidney replacement therapy [KRT]) or death. Repeated assessments of estimated glomerular filtration rate (eGFR). ANALYTICAL APPROACH: CKD progression and mortality before KRT were assessed by the cumulative incidence function methods and Fine and Gray models, with death handled as a competing event. Sex differences in eGFR slope were estimated using mixed effects linear regression models. RESULTS: 7,388 patients with incident CKD G3b, 18,282 with incident CKD G4, and 9,410 with incident CKD G5 were identified. Overall, 19.6 (95% CI, 19.2-20.0) patients per 100 patient-years progressed, and 10.1 (95% CI, 9.9-10.3) patients per 100 person-years died. Women had a lower risk of CKD progression (subhazard ratio [SHR], 0.88 [95% CI, 0.85-0.92]), and a lower all-cause (SHR, 0.90 [95% CI, 0.85-0.94]) and cardiovascular (SHR, 0.83 [95% CI, 0.76-0.90]) mortality risk. Risk factors related to a steeper decline in eGFR included age, sex, albuminuria, and type of primary kidney disease. LIMITATIONS: Incomplete data for outpatient visits and laboratory measurements and regional differences in reporting. CONCLUSIONS: Compared to women, men had a higher rate of all-cause and cardiovascular mortality, an increased risk of CKD progression, and a steeper decline in eGFR.

Preoperative chronic kidney disease and complications after pancreatoduodenectomy: a retrospective cohort study.

BACKGROUND: Chronic kidney disease is a prevalent condition in surgical patients. Possible associations with increased postoperative morbidity and mortality have not been clearly demonstrated in patients undergoing pancreatoduodenectomy. The aim of this study was to assess the risk of postoperative complications in patients with reduced kidney function undergoing pancreatoduodenectomy. METHODS: All patients undergoing pancreatoduodenectomy at Karolinska University Hospital between 2008 and 2019 were retrospectively included. The variable of interest was chronic kidney disease, based on preoperative estimated glomerular filtration rate measurements. Unadjusted and adjusted logistic regression analyses were performed for standardized postoperative complications. RESULTS: A total of 971 patients were included in the study, of whom 92 (10%) had an estimated glomerular filtration rate < 60 mL/min/1.73m2 , equivalent to chronic kidney disease Stage 3a or worse. Patients with chronic kidney disease had a higher odds of longer hospital stay (adjusted odds ratio 1.58, 95% confidence interval 1.00-2.50) and postoperative weight increase (adjusted odds ratio 2.02, 1.14-3.56). A 10 unit increase of preoperative estimated glomerular filtration rate was associated to lower odds of intensive care unit admission (adjusted odds ratio 0.81, 0.69-0.95), delayed gastric emptying (adjusted odds ratio 0.90, 0.81-0.99), and post-operative pancreatic fistula (adjusted odds ratio 0.83, 0.74-0.94). CONCLUSION: Patients undergoing pancreatoduodenectomy with decreased preoperative kidney function are more likely to experience major postoperative complications, and also postoperative weight increase. Preoperative kidney function assessment is important in risk stratification before pancreatoduodenectomies.

Kidney Function, Kidney Replacement Therapy, and Mortality in Men and Women.

Introduction: Women are more likely to have chronic kidney disease (CKD), compared with men, yet they are less likely to receive dialysis. Whether this sex disparity, which has predominantly been observed in nephrology-referred or CKD-specific cohorts so far, has a biological root cause remains unclear. Methods: We extracted general population data from the Stockholm CREAtinine Measurements project (SCREAM) (N = 496,097 participants, 45.5% men, 54.5% women). We used Cox regression to model male-to-female cause-specific hazard ratios (csHRs) for the competing events kidney replacement therapy (KRT, by dialysis or transplantation) and pre-KRT death, adjusted for baseline age, baseline kidney function (assessed via estimated glomerular filtration rate [eGFR] and eGFR slope), and comorbidities. Furthermore, we modeled sex-specific all-cause mortality by eGFR, again adjusted for age, eGFR slope, and comorbidities at baseline. Results: Compared with women, men were significantly more likely to receive KRT (fully adjusted male-to-female csHR for KRT 1.41 [95% CI 1.13-1.76]) but also more likely to experience pre-KRT death (csHR 1.36 [95% CI 1.33-1.38]). Differences between men and women regarding all-cause mortality by eGFR indicated a higher mortality in men at low eGFR values. Conclusion: Our data show that sex differences in CKD outcomes persist even after controlling for important comorbidities and kidney function at baseline. While future studies with a wider range of biological factors are warranted, these data suggest that nonbiological factors may be more important in explaining existing sex disparities in CKD progression and therapy.

Kidney Complications and Hospitalization in Patients With Chronic Hypoparathyroidism: A Cohort Study in Sweden.

CONTEXT: Kidney complications may be considerably higher in patients with chronic hypoparathyroidism (hypoPT) treated with activated vitamin D and calcium supplementation. OBJECTIVE: We aimed to investigate the risk of chronic kidney disease (CKD), urolithiasis, and hospitalization in patients with chronic hypoPT. METHODS: In this population-based cohort study in Sweden, national registries (Swedish National Patient Register, Swedish Prescribed Drug Register, and Total Population Register, 1997-2018) were used to identify patients with chronic hypoPT and controls matched by sex, age, and county of residence. We determined time to CKD and urolithiasis diagnosis, and incidence rates of hospitalization. RESULTS: A total of 1562 patients with chronic hypoPT without preexisting CKD and 15 620 controls were included. The risk of developing CKD was higher in patients with chronic hypoPT compared with controls (hazard ratio [HR] 4.45; 95% CI, 3.66-5.41). In people without prior urolithiasis (n = 1810 chronic hypoPT and n = 18 100 controls), the risk of developing urolithiasis was higher in patients with chronic hypoPT (HR 3.55; 95% CI, 2.84-4.44) compared with controls. Patients with chronic hypoPT had higher incidence rates for all-cause hospitalization (49.59; 95% CI, 48.50-50.70, per 100 person-years vs 28.43; 95% CI, 28.15-28.71, respectively) and for CKD (3.46; 95% CI, 3.18-3.76, per 100 person-years vs 0.72; 95% CI, 0.68-0.77, respectively), compared with controls. Men with hypoPT appear to have a higher risk of CKD than women. CONCLUSION: Patients with chronic hypoPT had an increased risk of CKD, urolithiasis, and hospitalization compared with controls.