Development and Internal Validation of a Multivariable Prediction Model for Mortality After Hip Fracture with Machine Learning Techniques.

In order to estimate the likelihood of 1, 3, 6 and 12 month mortality in patients with hip fractures, we applied a variety of machine learning methods using readily available, preoperative data. We used prospectively collected data from a single university hospital in Copenhagen, Denmark for consecutive patients with hip fractures, aged 60 years and older, treated between September 2008 to September 2010 (n = 1186). Preoperative biochemical and anamnestic data were used as predictors and outcome was survival at 1, 3, 6 and 12 months after the fracture. After feature selection for each timepoint a stratified split was done (70/30) before training and validating Random Forest models, extreme gradient boosting (XGB) and Generalized Linear Models. We evaluated and compared each model using receiver operator characteristic (ROC), calibration slope and intercept, Spiegelhalter's z- test and Decision Curve Analysis. Using combinations of between 10 and 13 anamnestic and biochemical parameters we were able to successfully estimate the likelihood of mortality with an area under the curve on ROC curves of 0.79, 0.80, 0.79 and 0.81 for 1, 3, 6 and 12 month, respectively. The XGB was the overall best calibrated and most promising model. The XGB model most successfully estimated the likelihood of mortality postoperatively. An easy-to-use model could be helpful in perioperative decisions concerning level of care, focused research and information to patients. External validation is necessary before widespread use and is currently underway, an online tool has been developed for educational/experimental purposes ( https://hipfx.shinyapps.io/hipfx/ ).

Association of routine hematological parameters with the development of monoclonal gammopathies: a case-control study of 134,740 patients : Resubmitted to annals of Hematology 26 March 2024.

The diagnosis of multiple myeloma requires detection of paraproteinemia and confirmation of monoclonal bone marrow infiltration, along with signs of end-organ damage. Despite the increasing prevalence, serum paraproteinemia is not routinely measured. We examined the relationship between alterations in routine hematological parameters and the development of paraproteinemia in a case-control study. Data was retrieved from a laboratory database in the capital region of Denmark between 01/01/2012 and 31/12/2022. Patients were included if they had a test for paraproteinemia (n = 134,740) and at least one prior hematological parameter (white blood cells, hemoglobin and platelet count) with a minimum follow-up of 1 year.Between 96,999 and 103,590 patients were included in each of the three hematological groups. We found white blood cell count and the presence of paraproteinemia followed an inverse J-shaped curve, with the highest presence below 3 × 109/L and above > 9 × 109/L. The adjusted OR below and above the nadir of 4 × 109/L was 1.61 (95% CI 1.25; 2.08, p < 0.0001) and 1.03 (95% CI 1.03; 1.04, p < 0.0001). Hemoglobin levels were inversely associated the presence of paraproteinemia, with the highest association below 6 mmol/L with an OR of 1.30 (95% CI 1.28; 1.32, p < 0.0001) adjusted for age and gender. Platelet count followed a U-shaped curve with the highest association at < 100 × 109/L. The adjusted OR below and above the nadir of 250 × 109/L was 1.13 (95% CI 1.10; 1.17, p < 0.0001) and 1.10 (95% CI 1.08; 1.12, p < 0.0001) respectively. In conclusion, all three parameters showed significant association with later paraproteinemia.

EUS-guided drainage of large walled-off pancreatic necroses using plastic versus lumen-apposing metal stents: a single-centre randomised controlled trial.

OBJECTIVE: In treating pancreatic walled-off necrosis (WON), lumen-apposing metal stents (LAMS) have not proven superior to the traditional double pigtail technique (DPT). Among patients with large WON (>15 cm) and their associated substantial risk of treatment failure, the increased drainage capacity of a novel 20-mm LAMS might improve clinical outcomes. Hence, we conducted a study comparing the DPT and 20-mm LAMS in patients with large WON. DESIGN: A single-centre, open-label, randomised, controlled superiority trial using an endoscopic step-up approach in patients with WON exceeding 15 cm in size. The primary endpoint was the number of necrosectomies needed to achieve clinical success (clinical and CT resolution), while the secondary endpoints included technical success, adverse events, length of stay and mortality. RESULTS: Twenty-two patients were included in the DPT group and 20 in the LAMS group, with no significant differences in patient characteristics. The median size of WON was 24.1 cm (P25-P75: 19.6-31.1). The technical success rates were 100% for DPT and 95% for LAMS (p=0.48), while clinical success rates were 95.5% and 94.7%, respectively (p=1.0). The mean number of necrosectomies was 2.2 for DPT and 3.2 for LAMS (p=0.42). Five patients (12%) developed procedure-related serious adverse events (DPT=4, LAMS=1, p=0.35). The median length of stay was 43 (P25-P75: 40-67) and 58 days (P25-P75: 40-86) in the DPT and LAMS groups (p=0.71), respectively, with an overall mortality of 4.8%. CONCLUSIONS: For treating large WON, LAMS are not superior to DPT. The techniques are associated with comparable needs for necrosectomy and hospital stay, and no gross difference in adverse events. TRIAL REGISTRATION NUMBER: NCT04057846.

Low-grade inflammation is negatively associated with live birth in women undergoing IVF.

RESEARCH QUESTION: Is low-grade inflammation, detected by C-reactive protein (CRP), a marker of IVF outcome addressing both blastocyst quality and pregnancy outcome? DESIGN: This sub-study of a multicentre randomized controlled trial included 440 women undergoing IVF treatment with a gonadotrophin-releasing hormone (GnRH) antagonist protocol. Serum CRP was measured on cycle day 2-3 (baseline) and on the day of ovulation triggering. The association between CRP concentrations and reproductive outcomes (number of retrieved oocytes, number of good-quality blastocysts, pregnancy, pregnancy loss and live birth), were analysed, adjusting for relevant confounders. RESULTS: A negative association was found between higher baseline CRP concentrations and live birth rate (odds ratio [OR] 0.77, 95% confidence interval [CI] 0.62-0.96, P = 0.02) and higher CRP concentrations at baseline were associated with pregnancy loss among women who conceived (OR 1.37, 95% CI 1.07-1.76, P = 0.01). When testing for a specific cut-off, CRP concentrations above 2.34 (the highest quartile) were more likely to be associated with pregnancy loss (P = 0.02) and a lower chance of live birth (P = 0.04) compared with the lowest quartile. No associations were found between CRP concentrations and pregnancy outcomes on the day of ovulation triggering, and there were no associations between CRP concentrations and the number of good-quality blastocysts. CONCLUSIONS: Higher CRP concentrations at cycle day 2-3, before starting ovarian stimulation, are negatively associated with chance of live birth, possibly because of an increased risk of pregnancy loss. No association was found between the number of good-quality blastocysts and CRP concentration. More studies are needed to investigate the impact of low-grade inflammation.

Vitamin D as a prognostic biomarker in COVID-19: single-center study and meta-analyses.

Vitamin D was investigated as a prognostic biomarker in COVID-19, in relation to both disease susceptibility and outcomes in infected individuals. Patients admitted to the hospital with a confirmed COVID-19 diagnosis were included if they had a vitamin D measurement prior to hospitalization. Using age- and sex-matched controls, vitamin D levels were investigated for an association with COVID-19 related hospitalizations. Further, vitamin D levels were investigated for an association with 30-day mortality in hospitalized COVID-19 patients. Additionally, three meta-analyses were conducted, investigating the association of vitamin D with the following outcomes: Having a positive SARS-CoV-2 test, hospitalization with COVID-19, and mortality in COVID-19 patients. A total of 685 hospitalized COVID-19 patients were included in the single-center study. Compared to controls, they had higher vitamin D levels. Unadjusted analysis of these 685 cases found higher vitamin D levels associated with increased 30-day mortality. This association disappeared after adjusting for age. In the fully adjusted model, no association between vitamin D and 30-day mortality was found. The meta-analyses found significant associations between lower vitamin D and having a positive SARS-CoV-2 test, and mortality among hospital-admitted COVID-19 patients. The relationship between lower vitamin D and COVID-19 related hospital admissions trended towards being positive but was not statistically significant. Many factors seem to influence the associations between vitamin D and COVID-19 related outcomes. Consequently, we do not believe that vitamin D in and of itself is likely to be a clinically useful and widely applicable predictor for the susceptibility and severity of COVID-19 infections.

Dysmagnesemia as a predictor of developing diabetic levels of hemoglobin A1c.

The aim of this study was to assess the possible association between P-Mg and subsequent high levels of HbA1c. The study involves data from primary health care patients and data from patients treated in hospitals located in the capital region of Denmark. P-Mg and HbA1c levels were analyzed from 121,575 patients in the period 2010-2022. Patients were categorized in a diabetic and non-diabetic group. Out of 121,575 patients, 8,532 were categorized as diabetic. A reverse J-shaped association between P-Mg and HbA1c levels ≥ 48 mmol/mol was observed with nadir at P-Mg of 0.90 mmol/L. The unadjusted hazard ratio (HR) for having a first HbA1c measurement ≥ 48 mmol/mol is 1.54 (95% Cl 1.50; 1.57) per 0.1 mmol/L decrease in P-Mg when P-Mg is lower than 0.90 mmol/L. After adjusting for age and gender, the HR remained significant at 1.45 (95% Cl 1.41; 1.48).For P-Mg levels above 0.90 mmol/L, the unadjusted HR per 0.1 mmol/L increase in P-Mg was 1.04 (95% Cl 1.02; 1.06). After adjusting for age and gender the HR remained significant at 1.06 (95% Cl 1.05; 1.08). In conclusion, this study found that patients with dysmagnesemia have a higher risk of developing diabetes even after adjusting for age and gender. Hyper- or hypomagnesemia in patients could be a biomarker for predicting the risk of developing diabetes.

The impact of anemia and blood transfusion on mortality after open abdominal surgery in the elderly.

BACKGROUND: Major abdominal surgery is associated with considerable mortality in the elderly. Anemia has been linked to increased mortality in other types of surgery, such as hip and cardiac surgery. This study aimed to assess the impact of preoperative anemia on mortality in the elderly undergoing major abdominal surgery, and how allogeneic red cell blood transfusion influences mortality in these patients. MATERIALS AND METHODS: We conducted a single-center, register-based retrospective study on patients, who were aged beyond 60 years and underwent one of 81 open abdominal surgical procedures. Patients operated on during the period from January 1, 2000, to May 31, 2013, were consecutively identified in the Danish National Patient Registry. Plasma hemoglobin was measured within 30 days prior to surgery and the primary endpoint was 30-day postoperative mortality. Information about patient transfusions from the hospital blood bank was available from 1998 to 2010. RESULTS: A total of 3199 patients were included of whom 85% underwent emergency surgery. The total mortality after 30 days was 20%. The median preoperative hemoglobin value of survivors was 7.7 mmol/L vs 6.9 mmol/L in those who died. The difference in hemoglobin values, between those who survived or died, decreased from the pre- to the post-operative phase. The 30-day postoperative mortality was 28%, 20%, and 12% in patients with a preoperative hemoglobin level in the lower, median, and upper quartile respectively. Transfusion therapy was associated with higher postoperative mortality, except in patients with very low hemoglobin values. CONCLUSION: Preoperative anemia has a clear association with surgically related mortality. The distribution of hemoglobin values in patients with a fatal outcome differs significantly from that of survivors. Red cell transfusion is associated with increased mortality, except in patients with very low hemoglobin values which supports recent guidelines suggesting a restrictive transfusion strategy.

Associations between education level, blood-lipid measurements and statin treatment in a Danish primary health care population from 2000 to 2018.

OBJECTIVE: To examine whether education level influences screening, monitoring, and treatment of hypercholesterolemia. DESIGN: Epidemiological cohort study. SETTING: Department of Clinical Biochemistry, Copenhagen University Hospital Hvidovre. SUBJECTS: Cholesterol blood test results ordered by general practitioners in Greater Copenhagen were retrieved from 2000-2018. Using the International Standard Classification of Education classification, the population was categorized by length of education in three groups (basic education; up to 10 years, intermediate education; 11-12 years, advanced education; 13 years or more). The database comprised 13,019,486 blood sample results from 653,903 patients. MAIN OUTCOME MEASURES: Frequency of lipid measurement, prevalence of statin treatment, age and comorbidity at treatment initiation, total cholesterol threshold for statin treatment initiation, and achievement of treatment goal. RESULTS: The basic education group was measured more frequently (1.46% absolute percentage difference of total population measured [95% CI 0.86%-2.05%] in 2000 and 9.67% [95% CI 9.20%-10.15%] in 2018) over the period compared to the intermediate education group. The advanced education group was younger when receiving first statin prescription (1.87 years younger [95% CI 1.02-2.72] in 2000 and 1.06 years younger [95% CI 0.54-1.58 in 2018) compared to the intermediate education group. All education groups reached the treatment goals equally well when statin treatment was initiated. CONCLUSION: Higher education was associated with earlier statin prescription, although the higher educated group was monitored less frequently. There was no difference in reaching treatment goal between the three education groups. These findings suggest patients with higher education level achieve an earlier dyslipidemia prevention intervention with an equally satisfying result compared to lower education patients.Key PointsLittle is known about the role of social inequality as a possible barrier for managing hypercholesterolemia in general practice.Increasing education level was associated to less frequent measurement and less frequent statin treatment.Patients with higher education level were younger, and less comorbidity at first statin prescription.Education level had no effect on frequency of statin treatment-initiated patients reaching the treatment goal was found.

Hospital-acquired anemia among patients in a university hospital and the affiliated general practices in the capital region of Denmark, 2019.

INTRODUCTION: Approximately 25% of the patients with hospital acquired anemia (HAA) develop moderate to severe HAA during hospitalization. This is related to an increased risk of prolonged stay, readmission and mortality. The primary aim was during one year to characterize a population with very frequent phlebotomies based on a university hospital in the Capital Region of Denmark and the related general practitioners. MATERIAL AND METHODS: We conducted a retrospective cohort study using administrative data on phlebotomies from 1 January 2019 to 31 December 2019 analyzed at a university hospital. RESULTS: A total of 203,811 patients had 10,083,207 requisitions and 1,373,013 tubes. One percent, 1985 patients, had an extreme of frequent phlebotomies >60 tubes and formed the basis for the study population. The study population was significantly older as compared to the excluded patients (<60 tubes) (mean 65.7 vs. 51.6 years, p < .001).The likelihood of hemoglobin decrease per 100 mL blood drawn were calculated at four levels of decreases: Hemoglobin decrease of 2 mmol/L (adjusted OR; 95%; 2.03, CI 1.79-2.31), hemoglobin decrease of 3 mmol/L (adjusted OR; 95%, 1.36, CI 1.28-1.45), hemoglobin decrease of 4 mmol/L, (adjusted OR; 95%, 1.27, CI 1.19-1.35) and hemoglobin decrease of 5 mmol/L, (adjusted OR; 95% 1.22, CI 1.13-1.31). CONCLUSIONS: Moderate to severe HAA occurred in a limited group with excessive many phlebotomies. It was a worrisome trend that the frailest patients had the highest risk of developing HAA.

Vitamin D levels and the risk of prostate cancer and prostate cancer mortality.

BACKGROUND: Vitamin D has a role in bone turnover and potentially bone-metastatic spread of prostate cancer (PCa). The aim of this observational study was to address the association between levels of serum vitamin D, diagnosis of PCa and subsequent mortality in men who underwent a biopsy of the prostate. METHODS: All men who underwent prostatic biopsy in the Danish PCa Registry (DaPCaR) and who had a serum vitamin D measurement during the period 2004 to 2010 (n = 4,065) were identified. Men were categorized by clinical cut-offs based on seasonally adjusted serum vitamin D levels in <25 (deficient), 25-50 (insufficient), 50-75 (sufficient) and >75 nmol/L (high) serum vitamin D. Logistic regression model for association between vitamin D and risk of PCa diagnosis and multivariate survival analyses were applied. RESULTS: No association between serum vitamin D and risk of PCa was found. Overall survival was lowest for serum vitamin D deficiency and a significantly higher PCa specific mortality (HR: 2.37, 95%CI: 1.45-3.90, p < .001) and other cause mortality (HR: 2.08, 95%CI: 1.33-3.24, p = .001) was found for PCa patients with serum vitamin D deficiency compared to serum vitamin D sufficiency. CONCLUSION: No association was found between serum vitamin D categories and risk of PCa in men who underwent biopsy of the prostate. Men with PCa and serum vitamin D deficiency had a higher overall and PCa specific mortality compared to men with a sufficient level of serum vitamin D.

Preoperative risk factors including serum levels of potassium, sodium, and creatinine for early mortality after open abdominal surgery: a retrospective cohort study.

BACKGROUND: In hospitalized patients, abnormal plasma electrolyte concentrations are frequent and have been linked to poor outcomes following acute surgery. The aim of this study was to assess whether preoperative plasma levels of potassium, sodium, and creatinine at the time of admission were associated with 30-day mortality in patients following open abdominal surgery. METHODS: This was a single-center register-based retrospective study. By means of electronic search in a maintained surgery database, all patients (n = 4177) aged ≥ 60 years old undergoing open surgery in our department from January 2000 to May 2013 were identified. Plasma was assessed within 30 days prior to surgery. The primary endpoint was 30-day postoperative mortality. The association between mortality and plasma levels of potassium, sodium, and creatinine were examined using Cox proportional hazard models. RESULTS: A total of 3690 patients were included in the study cohort. The rates of abnormal preoperative plasma levels were 36, 41, and 38% for potassium, sodium, and creatinine, respectively. The overall 30 day mortality was 20%. A predictive algorithm for 30 day mortality following abdominal surgery was constructed by means of logistic regression showing excellent distinction between patients with and without a fatal postoperative outcome. CONCLUSION: Apart from demographic factors (age, sex, and emergency surgery), preoperative imbalance in potassium, sodium and creatinine levels were significant independent predictors of early mortality following open abdominal surgery.

Vitamin D levels and cancer incidence in 217,244 individuals from primary health care in Denmark.

Vitamin D has been linked to cancer development in both pre-clinical and epidemiological studies. Our study examines the association between serum levels of vitamin D and cancer incidence in the Capital Region of Denmark. Individuals who had vitamin D analyzed at The Copenhagen General Practitioners Laboratory between April 2004 and January 2010 were linked to Danish registries with end of follow-up date at Dec 31st 2014, excluding individuals with pre-existing cancer. Cox regression models adjusted for age in one-year intervals, sex, month of sampling, and Charlson Comorbidity Index were applied. The study population of 217,244 individuals had a median vitamin D level of 46 nmol/L (IQR 27-67 nmol/L). Non-melanoma skin cancer was the most frequent form of cancer, followed by breast-, lung-, and prostate cancers. No associations were found between increments of 10 nmol/L vitamin D and incidence of breast, colorectal, urinary, ovary or corpus uteri cancer. However, higher levels of vitamin D were associated with higher incidence of non-melanoma (HR 1.09 [1.09-1.1]) and melanoma skin cancer (HR 1.1 [1.08-1.13]) as well as prostate (HR 1.05 [1.03-1.07]) and hematological cancers (HR 1.03 [1.01-1.06]), but with lower incidence of lung cancer (HR 0.95 [0.93-0.97]). In our study, vitamin D levels are not associated with the incidence of several major cancer types, but higher levels are significantly associated with a higher incidence of skin, prostate, and hematological cancers as well as a lower incidence of lung cancer. These results do not support an overall protective effect against cancer by vitamin D.

Comorbidity and mortality after hip fracture in nineteen thousand six hundred and eighty two patients aged eighteen to sixty five years in Denmark from 1996 to 2012.

PURPOSE: This nationwide study assessed associations between comorbidity and mortality after hip fracture in young and middle-aged patients. METHODS: Data on 19,682 patients aged 18 to 65 years were extracted from Danish registries out of 154,047 patients who experienced a hip fracture between 1996 and 2012. Mortality and comorbidity were assessed using information on vital status, hospital admissions, and prescriptions. RESULTS: Of the 19,682 patients 17,722 (90.0%) were middle-aged (40-65 years) and 1960 (10.0%) were young (18-39 years). The 30-day mortality rates were 3.2% (n = 570) and 1.6% (n = 32), respectively. Indicators of multi-trauma (hazard ratio (HR), 3.5 95% confidence interval (CI) [1.6-7.8], n = 2056) and having diabetes (HR, 4.4 [1.2-11.3], n = 59) and heart disease (HR, 4.4[1.3-14.8], n = 57) increased 30-day mortality in the young patients, while having cancer (HR, 5.0 [4.2-5.9], n = 1958) increased 30-day mortality in the middle-aged patients. CONCLUSION: Heart disease and diabetes were associated with high mortality in the young patients while having cancer was associated with high mortality in the middle-aged patients.

Role of light and the circadian clock in the rhythmic oscillation of intraocular pressure: Studies in VPAC2 receptor and PACAP deficient mice.

The intraocular pressure of mice displays a daily rhythmicity being highest during the dark period. The present study was performed to elucidate the role of the circadian clock and light in the diurnal and the circadian variations in intraocular pressure in mice, by using animals with disrupted clock function (VPAC2 receptor knockout mice) or impaired light information to the clock (PACAP knockout mice). In wildtype mice, intraocular pressure measured under light/dark conditions showed a statistically significant 24 h sinusoidal rhythm with nadir during the light phase and peak during the dark phase. After transfer of the wildtype mice into constant darkness, the intraocular pressure increased, but the rhythmic changes in intraocular pressure continued with a pattern identical to that obtained during the light/dark cycle. The intraocular pressure in VPAC2 receptor deficient mice during light/dark conditions also showed a sinusoidal pattern with significant changes as a function of a 24 h cycle. However, transfer of the VPAC2 receptor knockout mice into constant darkness completely abolished the rhythmic changes in intraocular pressure. The intraocular pressure in PACAP deficient mice oscillated significantly during both 24 h light and darkness and during constant darkness. During LD conditions, the amplitude of PACAP deficient was significantly lower compared to wildtype mice, resulting in higher daytime and lower nighttime values. In conclusion, by studying the VPAC2 receptor knockout mouse which lacks circadian control and the PACAP knockout mouse which displays impaired light signaling, we provided evidence that the daily intraocular pressure rhythms are primarily generated by the circadian master clock and to a lesser extent by environmental light and darkness.

Preoperative factors associated with red blood cell transfusion in hip fracture patients.

INTRODUCTION: Red blood cell (RBC) transfusion is a frequently used treatment in patients admitted with a fractured hip, but the use remains an area of much debate. The aim of this study was to determine preoperative factors associated with the risk of receiving a red blood cell transfusion in hip fracture patients. METHOD: The study included 986 consecutive hip fracture patients (aged 60 years or above). The patients were identified from a database of all hip fracture patients admitted to Bispebjerg University Hospital. Data for the database are collected via chart review and data extraction from the hospitals laboratory system, public registries and from the Capital Region Blood Bank Database. RESULTS: Overall transfusion rate was 58.7 %. The univariate analyses showed that transfusion rate was higher among women (p = 0.004), older patients (p < 0.0001), patients with high ASA scores (p < 0.0001), patients with more severe fractures (p < 0.0001), patients with lower admission haemoglobin levels (p < 0.0001), patients not admitted from own home (p = 0.02) and patients taking aspirin (p = 0.007) or other platelet inhibitors (p = 0.01) on admission. In the multivariate analysis, increasing age, ASA ≥3, being admitted from own home, extracapsular fractures, decreasing admission haemoglobin and use of platelet inhibitors were all significantly associated with the risk of receiving a RBC transfusion. CONCLUSION: Several readily available preoperative factors in the form of age, residence, ASA, admission haemoglobin, medication and type of fracture were independently associated with the likelihood of receiving a red blood cell transfusion in patients admitted with a fractured hip.

Early Switch From Intravenous to Oral Antibiotics for Patients With Uncomplicated Gram-Negative Bacteremia.

Importance: Gram-negative bacteremia is a global health concern, and optimizing the transition from intravenous (IV) to oral antibiotics is a critical step in improving patient treatment and resource utilization. Objective: To assess the association of switching to oral antibiotics within 4 days after initial blood culture with 90-day all-cause mortality compared with prolonged IV antibiotic treatment for patients with uncomplicated gram-negative bacteremia. Design, Setting, and Participants: This cohort study conducted using the target trial emulation framework included observational data from adults with uncomplicated gram-negative bacteremia in 4 hospitals in Copenhagen, Denmark, from January 1, 2018, through December 31, 2021. The duration of follow-up was 90 days. Eligibility criteria included a blood culture positive for growth of gram-negative bacteria, clinical stability within 4 days of initial blood culture, an available susceptibility report on day 4, and initiation of appropriate empirical IV antibiotic treatment within 24 hours of blood culture. Exposure: Switching to oral antibiotics within 4 days after initial blood culture compared with continuing IV antibiotic treatment for at least 5 days after initial blood culture. Main Outcomes and Measures: The main outcome was 90-day all-cause mortality. Inverse probability of treatment weighting was applied to adjust for confounding. Intention-to-treat and per-protocol analyses were performed using pooled logistic regression to estimate absolute risk, risk difference (RD), and risk ratio (RR); 95% CIs were computed using bootstrapping. Results: A total of 914 individuals were included in the target trial emulation analysis (512 [56.0%] male; median age, 74.5 years [IQR, 63.3-83.2 years]); 433 (47.4%) transitioned early to oral antibiotic treatment, and 481 (52.6%) received prolonged IV treatment. Ninety-nine individuals (10.8%) died during follow-up. The proportion of individuals who died was higher in the group receiving prolonged IV treatment (69 [14.3%] vs 30 [6.9%]). In the intention-to-treat analysis, 90-day all-cause mortality risk was 9.1% (95% CI, 6.7%-11.6%) for the early-switch group and 11.7% (95% CI, 9.6%-13.8%) for the group receiving prolonged IV treatment; the RD was -2.5% (95% CI, -5.7% to 0.7%) and RR was 0.78 (95% CI, 0.60-1.10). In the per-protocol analysis, the RD was -0.1% (95% CI, -3.4% to 3.1%) and RR was 0.99 (95% CI, 0.70-1.40). Conclusions and Relevance: In this cohort study of uncomplicated gram-negative bacteremia, early transition to oral antibiotics within 4 days of initial blood culture was associated with 90-day all-cause mortality risk comparable to that of continuing IV antibiotic treatment and may be an effective alternative to prolonged IV treatment.

Prediction of Admission to Intensive Care Unit and 1-Year Mortality After Acute Pancreatitis With Walled-Off Pancreatic Necrosis: A Retrospective, Single-Center Cohort Study.

BACKGROUND AND AIMS: Pancreatic walled-off necrosis (WON) carries significant mortality and morbidity risks, often necessitating intensive care unit (ICU) admission. This retrospective study aimed to evaluate whether routine biochemical parameters at the time of the index endoscopic procedure could predict ICU admission and 1-year mortality following endoscopic treatment of WON. MATERIALS AND METHODS: We retrospectively identified 201 consecutive patients who underwent endoscopic drainage for WON between January 1, 2010, and December 31, 2020. Associations between routine biochemical blood tests and outcomes were assessed using logistic regression models. RESULTS: Within 1 year of the index endoscopy, 31 patients (15.4%) died, and 40 (19.9%) were admitted to the ICU due to sepsis. Preoperative electrolyte disturbances were more prevalent among ICU-admitted patients and nonsurvivors. Hyperkalemia, hypoalbuminemia, and elevated urea were significant predictors of 1-year mortality, while hypernatremia, elevated serum creatinine, and hypoalbuminemia predicted ICU admission. Predictive models exhibited good discriminative ability, with an AUC of 0.84 (95% CI,0,75-0.93) for 1-year mortality and 0.86 (95%CI, 0.79-0.92) for ICU admission. CONCLUSIONS: Preoperative imbalances in routine blood tests effectively predict adverse outcomes in endoscopically treated WON patients.

Evaluating risk factors in recurrent pregnancy loss: A prospective cohort study and its impact on live birth outcomes.

Recurrent pregnancy loss (RPL) affects 1-2 % of all couples trying to conceive and is a challenging heterogeneous condition. This study aimed to evaluate the prevalence and impact of various risk factors in patients suffering from RPL. We performed a prospective cohort study including patients at the tertiary RPL Unit in the Capital Region of Denmark between 1st January 2000 and 1st January 2023. The main outcome of the study was the first pregnancy after referral and whether the pregnancy was ongoing at least to the 22nd gestational week. A total of 2555 patients were included in the study, out of whom 1892 patients achieved a pregnancy after referral to the RPL Unit. This resulted in 1103 live births (58.3 %) and 718 pregnancy losses (37.9 %). Maternal age, BMI, smoking status and the number of prior pregnancy losses were negatively correlated with the likelihood of achieving pregnancy. Furthermore, maternal age, prior pregnancy losses, antiphospholipid syndrome (APS) and uterine malformations were associated with reduced birth rates. Patients with secondary RPL had a higher birth rate compared to those with primary RPL, and patients with APS treated with low-molecular-weight heparin (LMWH) demonstrated a significantly increased birth rate compared to untreated APS patients. These findings suggest that certain risk factors significantly impact the likelihood of achieving pregnancy and live birth following RPL, which can be used in patient guidance.

Obesity Variants in the GIPR Gene Are not Associated With Risk of Fracture or Bone Mineral Density.

CONTEXT: It is not clear if antagonizing the GIP (glucose-dependent insulinotropic polypeptide) receptor (GIPR) for treatment of obesity is likely to increase the risk of fractures, or to lower bone mineral density (BMD) beyond what is expected with rapid weight loss. OBJECTIVE: The objective of this study was to investigate the risk of fracture and BMD of sequence variants in GIPR that reduce the activity of the GIP receptor and have been associated with reduced body mass index (BMI). METHODS: We analyzed the association of 3 missense variants in GIPR, a common variant, rs1800437 (p.Glu354Gln), and 2 rare variants, rs139215588 (p.Arg190Gln) and rs143430880 (p.Glu288Gly), as well as a burden of predicted loss-of-function (LoF) variants with risk of fracture and with BMD in a large meta-analysis of up to 1.2 million participants. We analyzed associations with fractures at different skeletal sites in the general population: any fractures, hip fractures, vertebral fractures and forearm fractures, and specifically nonvertebral and osteoporotic fractures in postmenopausal women. We also evaluated associations with BMD at the lumbar spine, femoral neck, and total body measured with dual-energy x-ray absorptiometry (DXA), and with BMD estimated from heel ultrasound (eBMD). RESULTS: None of the 3 missense variants in GIPR was significantly associated with increased risk of fractures or with lower BMD. Burden of LoF variants in GIPR was not associated with fractures or with BMD measured with clinically validated DXA, but was associated with eBMD. CONCLUSION: Missense variants in GIPR, or burden of LoF variants in the gene, are not associated with risk of fractures or with lower BMD.

Causes of death among 93.637 hip fracture patients- data based on the Danish National Registry of causes of death.

PURPOSE: Excess mortality among hip fracture patients is well documented. Less is known, however, about the causes of death in this group of patients, although existing literature suggests that bronchopneumonia and cardiovascular diseases constitute the leading causes of death. In this study, we investigated the causes of death in Danish hip fracture patients, who died within 30-days after sustaining a hip fracture, with a focus on differences in causes of death between men and women and between different age groups. Furthermore, the frequency of potentially preventable causes of death such as pneumonia, urinary tract infections and thromboembolic events was examined. METHODS: All Danish patients aged 18 or more suffering from a hip fracture in the period 2002-2012 were examined for inclusion into the study. Data were collected from the Danish National Patient registry. The last month of 2012 being December was left out since we were looking at 30-days mortality. Logistic regression analysis was used to test the association between 30-day mortality with each of the causes of death adjusted for age, sex and CCI in multivariable models with results presented as odds ratios (OR) with 95% confidence intervals. RESULTS: During this period, 93,637 patients sustained a hip fracture. Of these, 9504 patients died within 30-days and were included in the study. For patients dead within 30-days after sustaining a hip fracture, the two leading medical causes of death were cardiovascular disease (21.1%) and pneumonia (10.5%) when looking at both genders. A frequent cause of death especially in the younger age group of women less than 50 years old were infections (other than pneumonia) (18.2%) especially urinary tract infections. Pulmonary embolism accounted for 3.9% of causes of deaths in hip fracture patients. CONCLUSION: In this study, cardiovascular disease and pneumonia were overall the leading medical causes of death in patients dead within 30-days after sustaining a hip fracture. Apart from pneumonia, another potentially preventable infection in younger female hip fracture patients was urinary tract infections. Pulmonary embolism, another potentially preventable cause of death might be underreported in Danish death certificates.