Postoperative acute kidney injury (AKI) is a critical issue in geriatric patients with pre-existing chronic kidney disease (CKD) undergoing orthopedic trauma surgery. The goal of this study was to investigate modifiable intraoperative risk factors for AKI.A retrospective study was conducted on 206 geriatric patients with CKD, who underwent orthopedic trauma surgery. Several variables, including intraoperative blood loss, postoperative hypoalbuminemia, intraoperative blood pressure and long-term use of potentially nephrotoxic drugs, were analyzed.p < 0.001), postoperative hypoalbuminemia (p = 0.050), and potentially nephrotoxic drugs prior to admission  (p = 0.003). Furthermore, the AKI stage negatively correlated with propofol dose per body weight (p = 0.001) and there was a significant association between AKI and the use of cement (p = 0.027). No significant association between intraoperative hypotension and AKI was observed in any statistical test. Femur fracture surgeries showed the greatest blood loss , particularly intramedullary nailing at the proximal femur (598mL ± 395mL) and revision surgery (769mL ± 436mL).Postoperative AKI (KIDGO) was observed in 25.2% of the patients. The 1-year mortality rate increased significantly from 26.7% to 30.8% in patients who developed AKI. Primary risk factors for AKI were blood loss (In geriatric trauma patients with pre-existing CKD, intraoperative blood loss, postoperative hypoalbuminemia, and pre-admission use of potentially nephrotoxic drugs are associated with postoperative AKI. The findings highlight the necessity to mitigate intraoperative blood loss and promote ortho-geriatric co-management to reduce the incidence and subsequent mortality in this high-risk population. Acute kidney injury (AKI) is a common and serious complication following orthopedic and trauma surgeries, particularly in elderly patients with pre-existing chronic kidney disease (CKD). The incidence of AKI is high in major orthopedic surgeries (5—60%), and it has a negative impact on overall outcomes, including an increased 1-year mortality .Comorbidities such as CKD, diabetes mellitus, and cardiac insufficiency are well-known risk factors for the development of perioperative AKI in surgical patients . These fIn addition, trauma surgery presents a unique challenge as surgery is often urgently required regardless of the patient's previous illnesses. Therefore, it is crucial to identify intraoperative risk factors for the development of AKI that can be actively improved during surgery.Although some studies have examined AKI after orthopedic surgery, there is a notable gap in research specifically investigating the risk factors for acute-on-chronic kidney injury following trauma surgery in elderly patients , 3, 6. MAll patients undergoing surgery at a Level I Trauma Center between January 2021 and December 2021 were screened for inclusion in this study. Inclusion criteria were 65 years of age or older, surgery during the study period, and pre-existing CKD. Exclusion criteria were pre-existing dialysis requirement (at the time of admission), preoperative intensive care, ongoing or recently completed cytostatic therapy and pre-existing organ transplantation. For each patient, only the first surgery performed during the study period was considered. The primary outcome was acute kidney injury (AKI) as defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria.  The secoTo investigate potential risk factors for AKI, data was collected on a range of variables including patient diagnoses, blood pressure during surgery , drop in blood pressure during anesthesia, range of blood pressure, drugs used for anesthesia, dose of Propofol, duration/type of surgery, use of cement (without antibiotic infusion) and postoperative Albumin levels. Drop in blood pressure was defined as the difference between pre-anesthesia blood pressure and the lowest blood pressure recorded during anesthesia.Medication at admission, during hospitalization and at discharge were screened for potentially harmful drugs to the kidneys such as contrast mediums, angiotensin-converting enzyme inhibitors (ACE-I), angiotensin-II receptor antagonists (AT-II), diuretics, antibiotics (aminoglycosides), non-steroidal anti-inflammatory drugs (NSAID), and opiates.Additionally, blood loss during surgery was calculated using the Mercuriali formula . This foFor women, the formula isFor men, the formula isThe estimated blood loss is calculated asPostoperative Hct (hematocrit) values were accepted from days 4 to 6 after surgery. If necessary, (RBC) transfusions were administered based on the internal transfusion protocol, which mandated transfusions for patients with hemoglobin levels under 7 g/dl (provided the patient gave consent). Transfusions were also performed for patients with hemoglobin levels between 7 and 8 g/dl, depending on symptoms and cardiovascular risk factors.p-values ≤ 0.01 were considered highly significant. Exploratory data analyses were implemented to identify potential relationships between the risk factors and acute kidney failure. Differences were assessed for significance using ANOVA, Chi-Square or Fisher’s exact test, and correlations were examined using multiple linear regression and Spearman’s correlation.Data were collected from medical records and follow-up phone calls one-year post-surgery. These data were subsequently entered into a database for analysis using SPSS 28 . Information is represented as the mean ± standard deviation. The significance level was set to α ≤ 0.05, Prior to the data collection, a power analysis was conducted using G*Power 3.1.9.7 to determine the appropriate sample size. This was based on an estimated correlation of 0.2 between blood loss and AKI, as suggested by older data from a preliminary (in-house) study. The aim was to achieve a power greater than 80% and to set the level of significance  at ≤ 0.05. The power analysis recommended a sample size of 154. Considering the estimated annual patient eligibility of 200–300, the duration for sample collection was set at one year. The year 2021 was chosen as it was the most recent year for which complete 1-year survival data were available.This study complies with the ethical standards set forth in the Declaration of Helsinki and was approved by the Ethics Committee of the Bavarian State Medical Association (Bayerische Landesärztekammer) .A total of 206 patients were included . The average age of the participants was 82.77 ± 7.73 years, with a median age of 84 years, and an age range between 66 and 99 years. 52 of these patients (25.2%) developed an acute on chronic kidney injury within 7 days after surgery. The injuries sustained by the patients were diverse, with 40 fractures of the upper extremity, 2 pelvic fractures, 125 fractures of the lower extremity, 16 spinal fractures, and 23 other types of injuries. Overall, the 1-year mortality rate was 26.7% (55/206). For patients who developed postoperative AKI, the 1-year mortality rate was even higher, at 30.8% (16 of 52).p < 0.001) and transfusion volume (in mL) (p < 0.001) with the AKI stage according to the KDIGO criteria. A significant negative correlation was observed between postoperative albumin levels and AKI (p = 0.050), indicating that lower albumin levels were associated with a higher incidence of AKI. Furthermore, a significant negative correlation was found between the induction dose of propofol (in mg) and AKI stage (p = 0.007), as well as between the induction dose of propofol per bodyweight (in mg/kg) and AKI stage (p = 0.001). There was a significant positive relationship between the induction dose of propofol per body weight and the minimum mean arterial pressure (MAP) during surgery (p = 0.033). No significant association between intraoperative hypotension and AKI was observed in any statistical test. Different risk factors for the development of AKI are presented in Table A Spearman correlation test showed a significant positive correlation between blood loss (in mL) p < 0.00 and tranp = 0.02), with blood loss standing out as a paramount risk factor, as indicated by a highly significant (p = 0.001) and an R-value of 0.309. Given that the risk score includes blood loss, albumin, and nephrotoxic medications, it is not independent of these factors. Hence, an additional multiple linear regression analysis was performed without these variables, revealing also the risk score as highly significant .Additionally, a multiple linear regression analysis was conducted, incorporating blood loss, Propofol/bodyweight, min MAP, time systolic < 80 mmHg, time systolic < 70 mmHg, and min systolic pressure. The results of this analysis yielded significant differences (p = 0.027), as well as between AKI stage (KIDGO) and postoperative hypoalbuminemia  (p = 0.031). A significant association was found between the preoperative use of potentially nephrotoxic medications as part of the patients’ long-term medication regimen and the development of AKI (p = 0.028). Potentially nephrotoxic medications included diuretics (except Torasemide ≤ 10 mg/day), angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), and nephrotoxic antibiotics.Chi-square test and Fisher's exact test showed a significant association between the AKI stage (KIDGO) and the use of cement , blood loss greater than 500 mL, and blood loss greater than 1000 mL Table .Table 2Dp = 0.662).The incidence of AKI varied across different injury types, being highest for femur fractures  and absent for lower leg/foot fractures (0/7). An ANOVA test revealed these differences in AKI incidence were not statistically significant (p = 0.005). Post hoc multicomparison analysis than confirmed a significant difference between forearm/hand fractures and Femur fractures   and revision surgeries (average 505 mL ± 477 mL), and the lowest for forearm (average 201 mL ± 150 mL) and lower leg fractures (average 233 mL ± 227 mL). ANOVA identified a highly significant difference between the groups (p = 0.060) , followed by intramedullary nailing (average 598 mL ± 395 mL), hemi-arthroplasty (average 430 mL ± 243 mL) and total-arthroplasty (average 421 mL ± 337 mL)(ANOVA p = 0.050), implying that lower albumin levels were associated with an increased likelihood of AKI. Albumin levels also significantly negatively correlated with the 1-year mortality rate . A highly significant correlation was detected between postoperative albumin levels and the induction dose of propofol . Moreover, a significant negative correlation was found between the duration of the surgery and postoperative albumin levels , suggesting that longer surgeries were associated with lower postoperative albumin levels.A significant negative correlation was observed between postoperative albumin levels and the development of AKI  of these factors. Within this model, 1-year-mortality (p = 0.009) and duration of surgery (p < 0.001) demonstrated highly significant associations with postoperative serum albumin levels. However, the links with acute kidney injury (AKI) (p = 0.110) and Propofol induction dose (p = 0.250) did not reach statistical significance.Further analysis utilizing a multiple linear regression model displayed a highly significant overall effect  in the Chi-square and exact Fisher's test, as well as in the multiple linear regression . With an odds ratio of 9, these high-risk patients have a highly increased risk of developing AKI in the immediate postoperative period compared to patients with lower scores. The high-risk score demonstrated a positive predictive value of 71.4% and a negative predictive value of 78.3%, indicating its effectiveness in identifying patients at risk of developing AKI.Patients with a score of 3 or higher were classified as high-risk patients. The score showed a highly significant association with the occurrence of AKI (p < 0.001). Lastly, a significant positive correlation was found between the duration of the surgery and the number of days by which the surgery was postponed , indicating that a longer delay in surgery was associated with a longer operative time.The analysis revealed a significant positive correlation between blood loss and transfusion volume (Spearman's correlation coefficient 0.222; In this study, the incidence and risk factors of postoperative AKI in geriatric patients with pre-existing CKD undergoing orthopedic trauma surgery were examined. A high incidence of postoperative AKI was observed at 25.2%. It was noted that the incidence of AKI significantly increased the 1-year mortality rate from 26.7 to 30.8%, a finding that aligns with the existing literature which points to a higher mortality associated with AKI .The primary risk factors for AKI development in this study's cohort were found to be blood loss, postoperative hypoalbuminemia, and the long-term administration of potentially nephrotoxic drugs prior to admission. Contrary to some literature, intraoperative hypotension did not emerge as a significant risk factor for AKI in this study , 12.Postoperative hypoalbuminemia is a recognized risk factor for postoperative AKI, and this study also identified a significant correlation . AlbuminHypoalbuminemia, beyond its correlation with AKI, demonstrated a statistically significant association with higher 1-year mortality. This link is likely multifactorial, reflecting not only the impact of hypoalbuminemia on renal function but also its role as an indicator of malnutrition or severe underlying diseases . These cThe observed significant correlation between albumin levels and the induction dose of propofol can be rationalized considering the pharmacokinetics of propofol. Propofol is highly protein-bound, with over 98% of it binding primarily to hemoglobin and albumin . ConsequFurthermore, in this study, a significant negative correlation was observed between the induction dose of propofol and the development of AKI, suggesting that propofol may confer a protective effect on renal function. Interestingly, this possible protective effect of propofol aligns with the findings of a randomized controlled trial conducted on cardiac surgery patients, which demonstrated a protective effect of propofol in comparison to sevoflurane .Indeed, postoperative albumin levels provide critical insights into the probability of AKI occurrence . HoweverPotentially nephrotoxic medications at the time of admission are also a well-known risk factor and have been identified as a significant influence in the present study . HoweverGreater opportunities for intervention present themselves with blood loss. Consistent with other publications, this study identified blood loss as one of the greatest risk factors for postoperative AKI . SurgeonThe risk score used in this study, which includes blood loss, medication at admission, and postoperative serum albumin, showed good predictive values for an increased risk of acute-on-chronic kidney failure in geriatric patients. Various risk scores have been suggested in the literature to evaluate perioperative AKI risk , 25. HowThrough the now widespread implementation of ortho-geriatric co-management, optimal postoperative care and early detection of AKI should be generally ensured , 26, 27.Despite numerous publications on perioperative AKI risk, to our knowledge, no study to date has specifically addressed the risk group of geriatric patients with pre-existing CKD in trauma surgery , 12, 20.The multifactorial nature of AKI poses an inherent challenge to this study, as it entails numerous confounding factors. Despite our best efforts to meticulously test and evaluate potential risk factors, as informed by the existing literature, a complete exclusion of further influences remains elusive in this retrospective study design. The correlations observed in this study were mathematically defined as “weak”. Nevertheless, they are of significance as they were either statistically significant or highly significant. Importantly, given the multitude of factors contributing to AKI, such “weak” correlations were to be expected. Moreover, these findings align with the existing body of knowledge and literature, reinforcing their scientific validity and relevance. Unfortunately, due to the retrospective design, it was not possible to gather adequate data on the further course of CKD for enough patients. This would be highly interesting, especially in light of the mutual influence of AKI and CKD . TherefoStrengths of this study include its focus on a highly relevant patient group with a high risk of complications and a high 1-year mortality rate, as well as its emphasis on modifiable parameters relevant for treatment. Despite the stringent inclusion and exclusion criteria, a sufficient case number was achieved to investigate various influencing factors. Furthermore, the study was able to identify intraoperative blood loss as a key factor for the development of perioperative AKI in elderly trauma patients with preexisting CKD.In summary, for patients at high risk of developing perioperative AKI, we recommend choosing surgical procedures with the least anticipated blood loss and implementing measures to reduce blood loss, such as the local and/or systemic use of tranexamic acid. Furthermore, ortho-geriatric co-management is advisable to ensure adequate postoperative care—especially focusing on early diagnosis and treatment of complications like AKI.Blood loss, postoperative hypoalbuminemia, and potentially nephrotoxic medications at admission are the strongest risk factors for the development of acute-on-chronic kidney injury in geriatric trauma patients. Blood loss has proven to be a modifiable and statistically highly significant influencing factor. Therefore, we recommend—especially in this patient clientele with a high risk of developing perioperative AKI—to take all available measures to keep blood loss as low as possible.


Cardiovascular (CV) complications are important causes of morbidity and mortality in children after kidney transplantation (KTx). In adults, central blood pressure (cBP) is an accepted predictor of CV sequelae. We aimed to assess the prognostic value of cBP over peripheral blood pressure (pBP) for existing CV damage.We measured cBP and pBP in 48 pediatric KTx recipients (mean age: 13.5 ± 4.2 years). Assessment of left ventricular mass index (LVMI) and aortic pulse wave velocity (PWV) allowed detection of CV target organ damage. LVMI and PWV were used as endpoints in multivariable linear regression models, in which cBP and pBP were compared for their predictive value.Using cBP z-scores, we identified a larger number of patients with uncontrolled or untreated hypertension compared to pBP (36% vs. 7%). Central systolic blood pressure (cSBP) was a significant independent predictor of LVMI, while peripheral systolic blood pressure (pSBP) was not. Comparing central (cDBP) and peripheral (pDBP) diastolic blood pressure for their predictive value on PWV revealed a greater estimate for cDBP (0.035 vs. 0.026 for pDBP) along with a slightly better model fit for cDBP.Our data in a small group of patients provide first evidence that cBP measurements in pediatric KTx recipients might be helpful in identifying patients at risk for the development of CV sequelae. Investigating a larger patient number, ideally repeatedly, is needed to create further evidence supporting our findings. In light of available devices measuring cBP noninvasively, the implementation of such clinical studies post-KTx care should be feasible.The online version contains supplementary material available at 10.1007/s00467-022-05857-y. Children after kidney transplantation (KTx) suffer from a high cardiovascular (CV) burden and CV events are still among the most important causes of morbidity and mortality in these patients , 2. EarlThe prevalence of arterial hypertension is high in pediatric KTx recipients , 10. It As no data for children after KTx currently exist, we aimed to examine the predictive value of cBP over pBP for existing CV damage detected by measurement of PWV and left ventricular mass index (LVMI) in pediatric KTx recipients. We used the Mobil-O-Graph as it not only has been validated against invasive recordings in children and adults , 22, butth percentile) and < 1.645 (< 95th percentile) of sex-specific z-score range; obesity was defined as BMIz ≥ 1.645 (95th percentile) age and sex-specific z-score [For this prospective study, we examined a total of 48 children, adolescents, and young adults, who received KTx before the age of 18 years. We included only patients with a functioning graft. Patient data  and current medication information were obtained from the medical charts. Blood samples were obtained and analyzed in a central laboratory . The analysis included creatinine, cystatin C, and urea. Estimated glomerular filtration rate (eGFR) was calculated as proposed by Schwartz et al. (0.41 × height (cm)/plasma-creatinine (mg/dl)) . Z-score z-score . The stuth percentile) [th percentile) were considered elevated. Further classification of elevated BP also considered the use of antihypertensive medication. We defined patients on antihypertensive medication displaying elevated BP values as having “uncontrolled hypertension,” while those with normotensive BP were classified as “controlled hypertension.” Patients who did not receive antihypertensive drugs but displayed elevated BP values were classified as having “untreated hypertension.”BP measurements were performed as follows: pBP was measured using a validated oscillometric device  after 5 min of rest in a seated position on the right and left arm, one measurement each. pBP z-scores (pBPz) were calculated according to the reference values from the National High Blood Pressure Education Program Working Group in Children and Adolescents . cBP wascentile) . SimilarPWV was measured using the oscillometric Vicorder device  following a standardized protocol in accordance with the current guidelines  as repor2.16 were considered to have LVH.Transthoracic echocardiography was performed using a Philips CX 50 ultrasound device , equipped with a 1–5-MHz transducer, according to the recommendations of the American Society of Echocardiography . All stupBP and cBP were measured sequentially by a study nurse or a trained medical student. The devices were set to measure BP with mentioned repeats and results were stored in the devices’ data cache until all examinations were performed. Measurements were then transferred to the study’s case report form. Echocardiography was performed and evaluated by a single pediatric cardiologist. PWV was measured by two experienced physicians. None of the physicians was aware of the blood pressure examinations.t-test was used for paired comparison of cBPz and pBPz and paired ANOVA for cBP-C1, cBP-C2, and pBP. Multiple comparisons were corrected with the Tukey adjustment. Multivariable linear regression analyses for LVMI and PWV were performed to investigate the effect of pBP, cBP-C1, and cBP-C2, adjusted for sex, age [R2, was considered for the comparison of predictive values between cBP-C1, cBP-C2, and pBP on LVMI or PWV. A two-tailed p-value of < 0.05 was considered statistically significant. Statistical analysis was performed using the SAS Enterprise Guide 7.1 .Data are given as mean ± standard deviation (SD) or frequency and percentage. Paired sex, age , 33, 36,sex, age , 37, 38.2 (z-score 0.3 ± 1.0). Congenital anomalies of the kidney and urinary tract (CAKUT) as the underlying disease was found in 32 patients (67%). Mean time since last transplantation was 5.5 ± 4.6 years, 20 patients (42%) were transplanted preemptively, and 4 (8%) received a re-transplantation. Mean eGFR was 76.8 ± 37.5 ml/min/1.73 m2. The majority of patients  received a calcineurin inhibitor–based immunosuppression  in combination with either mammalian target of rapamycin (mTOR) inhibitors  or mycophenolate mofetil . Twenty-three (48%) patients were on steroids.We included 48 pediatric KTx recipients in the study. Mean age was 13.5 ± 4.2 years (range 5–24 years), 22 (46%) were girls, mean height was 151.3 ± 21.2 cm (z-score − 0.4 ± 1.3), and mean BMI was 20.7 ± 4.3 kg/mTable Mean pSBP and pDBP were 113.2 ± 10.5 mmHg and 67.0 ± 10.3 mmHg, respectively. Five children (10%) had elevated pSBP, and three children (6%) had elevated pDBP values.p < 0.001); for diastolic absolute values, there was no significant difference as presented in Fig. The Mobil-O-Graph provides C1 and C2 values based on two calibration methods. Mean cSBP-C1 and cDBP-C1 were 107.4 ± 8.8 mmHg and 73.3 ± 9.0 mmHg, while mean cSBP-C2 and cDBP-C2 were 116.5 ± 13.4 mmHg and 72.7 ± 9.1 mmHg. As illustrated in Fig. p = 0.03), with no difference between cSBP-C2 and pSBP   Fig. .Based on SBP z-scores from pBP and cBP measurements and the use of antihypertensive medication, we aimed to group patients as being normotensive or having untreated, uncontrolled, or controlled hypertension. Based on pSBPz, we identified three (7%) patients having uncontrolled hypertension, 33 (79%) with controlled hypertension, and six (14%) had normotensive pBP values Fig. . Using cAs higher BP is known to cause CV damage, we evaluated the effect of pBP and cBP on LVMI and PWV, which we had measured in the majority of patients from our cohort.2.16. Left ventricular hypertrophy was found in ten (21%) patients. We composed a multivariable linear regression model predicting LVMI and adjusted for sex, age, eGFR, and pSBP (Table p = 0.04). In addition, the model including cSBP-C2 showed a superior fit (R2 = 0.182) when compared to the model including either pSBP (R2 = 0.156) or cSBP-C1 (R2 = 0.112).LVMI values were available for 47 patients. Mean LVMI was 38.3 ± 11.0 g/mPWV values were available for 43 patients. Mean absolute values for PWV were 5.6 ± 0.7 m/s, and the mean PWVz was 1.1 ± 1.1. Sixteen (37%) patients had an elevated PWVz.R2 = 0.462 and R2 = 0.469 vs. R2 = 0.453; Table Similar to what we had done for LVMI, we composed a multivariable linear regression model predicting PWV adjusted for sex, age, eGFR, and either pSBP or pDPB. We showed that higher pDBP was significantly and independently associated with higher PWV, while pSBP was not. Therefore, we used pDBP for the remaining analysis. Age, but neither sex nor eGFR, was an independent predictor of PWV. Introduction of either cDBP-C1 or cDBP-C2 revealed that both values were independently associated with higher PWV. We found higher estimates for cDBP-C1 and cDBP-C2 (0.033 and 0.035) compared to pDBP (0.026) along with a slightly better model fit for the cDBP-C1 and cDBP-C2 Below is the link to the electronic supplementary material.


BackgroundSevere disease from COVID-19 was the leading cause of admission to the emergency room and hospitalization during the pandemic in Mexico. Acute kidney injury was one of the most prevalent complications in these patients. The neutrophil/lymphocyte (NL) index and the neutrophil/lymphocyte platelet (NLP) index have previously been described as possible markers associated with complications and mortality in this disease.ObjectiveTo determine the association of the NL ratio and the NLP ratio in patients with acute kidney injury secondary to severe COVID-19.Materials and methodsThis is a case-control study, unpaired, of patients diagnosed with severe COVID-19 who presented or did not present acute kidney injury. On admission to the hospital, the hematological ratios were calculated, and Mann-Whitney U tests and multivariate logistic regression were performed.ResultsA total of 160 patients were included, and a difference in the NLP ratio  was observed between patients with and without acute kidney injury. Additionally, the NLP ratio was the main risk variable for acute kidney injury in severe COVID-19, with an odds ratio of 2.5 and a 95% confidence interval of 1.108-5.66.ConclusionsThe NLP ratio has a moderate association and is a risk factor associated with the presence of acute kidney injury in patients with severe COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is diagnosed in patients who meet the COVID-19 definition, have a positive polymerase chain reaction (PCR) test, and exhibit clinical signs of pneumonia along with one of the following: SpO2 < 94% on room air, a ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/Fio2) < 300 mmHg, a respiratory rate ≥ 30 breaths/minute, or lung infiltrates > 50% [Acute kidney injury is a frequent condition in patients with severe COVID-19 disease -4. The pThe proposed pathophysiological mechanism for renal injury in COVID-19 is related to the ability of SARS-CoV-2 to affect tissues expressing the angiotensin-converting enzyme 2 (ACE2) receptor -12, leadAmong the wide range of inflammatory markers, hematologic cell indices such as the neutrophil/lymphocyte (NL) ratio and the neutrophil/lymphocyte platelet (NLP) ratio have been described as potential markers associated with or predictive of acute kidney injury in various scenarios, including cardiac surgery, sepsis, and major abdominal surgery ,18.Specifically, in COVID-19, it has been observed that the NL ratio increases the risk of mortality in COVID-19 patients . Furthermore, an NLP ratio greater than 3 has been identified as a risk factor for acute kidney injury in the intensive care COVID-19 sepsis setting  .However, the association of these two indices with acute kidney injury in patients with severe COVID-19 disease has not been compared from the time of hospital admission. Therefore, the main objective of this study is to determine the association between the NL ratio and the NLP ratio with acute kidney injury in severe COVID-19.Following authorization from the local ethics and research committees , a non-matched case-control study was conducted at Hospital General León. All patients over 18 years old with a diagnosis of severe COVID-19  during tIn all patients, hematological indices were calculated at hospital admission using absolute values from the complete blood count: (a) the NL index was calculated using the formula: neutrophils/lymphocytes; and (b) the NLP index was calculated using the formula: (neutrophils * 100)/(lymphocytes * platelets).Additionally, the following data were collected from the medical records: severity of renal injury, use of renal replacement therapy  during hospitalization, length of hospital stay, and hospital outcome .Statistical analysisCategorical variables are described as percentages and quantitative variables are described as means (standard deviation) or medians (interquartile range) depending on the normality of the data (Kolmogorov-Smirnov test).An independent samples t-test or Mann-Whitney U test was performed to evaluate the difference in means or medians of the hematological indices, respectively. A receiver operating characteristic (ROC) curve analysis was conducted, obtaining the area under the curve (AUC) with a 95% confidence interval using Youden's index (sensitivity + specificity - 1) to determine the optimal cutoff point for each index; furthermore, a Cohen's d test was conducted to assess the association of the NL ratio and NLP ratio with acute kidney injury.Finally, a multiple logistic regression analysis was performed  to obtain odds ratios (OR) with a 95% confidence interval, identifying the main variables associated with the probability of developing acute kidney injury. In this study, a p-value ≤ 0.05 was considered statistically significant.A total of 160 patients who met all the selection criteria were included in the final analysis. Among them, 52.5% were male, with a mean (±SD) age of 58 years (±14 years) and a BMI of 29.8 kg/m2 (±5 kg/m2). The study population consisted of 59% of patients with type 2 diabetes mellitus and 83.8% with criteria for acute respiratory distress syndrome, of which 36.2% required mechanical ventilation. Upon admission, the median (IQR) values for the NL index, NLP index, and creatinine were 8.63 (4.2-15), 4.2 (2.8-8.7), and 0.9 mg/dl (0.5-1.2 mg/dl), respectively. The prevalence of acute kidney injury was 38.7%, and the overall mortality rate was 12.5%; additionally, a mortality rate of 21% was identified  . However, the NLP index showed a significant difference on the first day between the groups . The ROC curve analysis revealed an AUC of 0.523  for the NL index and 0.670  for the NLP index .Finally, when analyzing the outcomes of the study population, a significant difference was observed in the medians of the NLP index between patients discharged from the hospital and those who died  being a single-center and retrospective study; (2) due to the nature of the population and the study's timeline, a matched case-control study could not be conducted to control factors like age, gender, or BMI; (3) despite being limited to patients without shock status, being a retrospective study meant no control over other confounding variables such as the occurrence of infectious processes in the first seven days of evaluation, patients with ARDS who exhibited kidney-lung interaction, or hematological alterations caused by the use of steroids or IL-6 blockers, which could have introduced bias in the causal relationship between the measured hematological associations and acute kidney injury; and (4) similarly, being a retrospective study, it was not possible to ensure proper standard care in the follow-up of mechanically ventilated patients outside the intensive care setting.The NLP ratio has a moderate association with acute kidney injury and is a potential risk factor in patients with severe COVID-19. Furthermore, an increase in the NLP ratio raises the risk of in-hospital mortality in patients with severe COVID-19, whether or not they have acute kidney injury.


Background and Objectives: Carotid intima–media thickness (CIMT) and obesity are considered independent determinants of cardio- and cerebrovascular events. The aim of our study was to investigate the effect of obesity on CIMT and to define which traditional cardiovascular risk factors correlate the most with CIMT values in patients with obesity. Materials and Methods: Anthropometric measurements were collected for the whole study group, as well as body composition and blood pressure data, and biochemical blood analyses were also performed. Results: Although our study group was significantly older according to vascular compared with chronological age, the mean CIMT values were lower when compared with the reference values. We found a statistically significant correlation of CIMT with chronological and vascular age, systolic blood pressure, fasting glucose, total cholesterol and triglyceride levels, waist-to-hip ratio, waist circumference, body muscle mass and skeletal muscle mass index. Atherosclerotic Cardiovascular Disease (ASCVD) risk assessment and SCORE  showed significant positive correlations, but there was only a weak correlation of ASCVD with CIMT. Conclusions: To deduce, since no diagnostic tool currently includes body weight as an individual risk factor, further trials are highly needed to determine if SCORE, SCORE2, ASCVD risk assessment or CIMT would be the most accurate and relevant diagnostic tool for prediction of risk for future CV events in patients with obesity. Carotid intima–media thickness (CIMT) and obesity are considered independent determinants of cardio- and cerebrovascular events. Obesity is associated with increased cardiovascular disease in primary prevention, but in secondary prevention, mortality is often lower in people with normal body weight . The assThis cross-sectional study was conducted at the Croatian Referral Center for Obesity Treatment  and at the TIA Clinic of the University Hospital Center Zagreb, Croatia. The study was approved by the hospital’s Ethics Committee. All the participants signed an informed consent form. Overall, the study was conducted in accordance with the Declaration of Helsinki.2 and age > 18 years. The exclusion criteria were pituitary and/or adrenal disease, untreated thyroid disease, prior myocardial infarction, stroke, TIA or oncological disease. Patients’ weight (kg), height (m), hip (cm), waist  (cm) and neck circumference  (cm) were measured; body mass index (BMI) (weight/height2), waist-to-hip ratio  were calculated [2) and fat mass index (FMI) (kg/m2). The information on smoking status (non-smoker and current smoker), diabetes, hypertension, number of years taking antihypertensive drugs and number of years living with obesity was recorded for each patient. We included 101 patients with obesity of both genders. The inclusion criteria were BMI ≥ 30 kg/mlculated . Body coBlood pressure was measured with an OMRON digital sphygmomanometer on both arms after at least 10 min of rest. Mean values were determined from two independent measurements. Patients with systolic blood pressure (SBP) below 140 mmHg and diastolic blood pressure (DBP) below 90 mmHg were considered normotensive. Patients with average blood pressure above 140/90 mmHg or those who took antihypertensive medication were put in the hypertensive group. Vascular age was determined by using color cardiovascular risk scales from the SCORE  . AtherosThe biochemical analyses in all patients included fasting glucose, fasting insulin, plasma glucose 2 h after a 75 g oral glucose load, total cholesterol, LDL and HDL cholesterol, triglycerides and thyrotropin. Thyrotropin was obtained with ECLIA Roche . Plasma glucose was measured by a glucose-oxidase method. Plasma total cholesterol, HDL cholesterol, and triglycerides were assessed with standard enzymatic spectrophotometric techniques. Plasma insulin was measured by radioimmunoassay. HOMA-IR was calculated with the formula: fasting plasma glucose (mmol/L) times fasting serum insulin (mIU/L) divided by 22.5, according to the method previously described and standardized elsewhere .CIMT was measured according to the Mannheim protocol using a linear ultrasound transducer (3–12 MHz) . Patientp) and Spearman’s  correlation methods for parametric and non-parametric distributions, respectively. For the categorical variables, the differences were determined with the Chi-square test. Differences between two groups were determined with the parametric t-test or non-parametric Mann–Whitney test, whilst for comparison between three or more groups, an ANOVA test was used. Univariable linear regression analysis was performed to examine which demographic and clinical variables were significant predictors for the mean CIMT. Variables for analysis were included based on clinical significance. Statistically significant predictors were included in the multivariable linear regression model. p values of less than 0.05 were considered significant. Statistical analysis was performed using SPSS 25 software . To assess the distribution of the data, the Kolmogorov–Smirnov test was applied. Variable values were described by absolute and relative frequencies, central tendency measures, and spread measures. Associations between variables were tested with Pearson’s , the mean CIMT value was calculated and used in further statistical analysis. The average mean CIMT value was 0.583 ± 0.122 (range 0.315–1.050) mm. There was no statistically significant difference in mean CIMT values between a male and female group of patients .The study included a total of 101 patients with obesity, 75 (74.3%) of whom were female. The main characteristics of the study group are presented in p < 0.001; confined to patients who had the vascular age calculated). The mean age of the study group was 49.02 ± 12.52 years, with the youngest being 22 and the oldest 78 years. Vascular age was calculated according to the cardiovascular risk scales from the SCORE project [p = 0.588 and rp = 0.421, respectively, all p values < 0.01). Scatter plots showing the CIMT values dispersion over age are presented in p = 0.197). See The mean CIMT values showed a significant positive correlation with both chronological and vascular age (rp = 0.384). See The percentage of patients in groups divided according to the obesity grade is presented in We found statistically significant positive correlations between mean CIMT values and body muscle mass, SMI, waist circumference and WHR. A Scatter plot showing the distribution of CIMT values over WHR values is presented in p < 0.001), whereby patients with hypertension had higher values of mean CIMT. The values of systolic blood pressure showed a significant positive correlation with mean CIMT values, although the diastolic blood pressure and the duration of arterial hypertension did not show any effect on CIMT. Arterial hypertension was present in 59.4% of patients, with a mean duration of 7.18 ± 5.88 years. There was a statistically significant difference in mean CIMT values between groups with and without arterial hypertension , or between the groups with and without prediabetes . No statistically significant correlation was noted between the duration of diabetes and mean CIMT. The mean CIMT values showed a statistically significant positive correlation with fasting glucose levels, but not with glucose levels after two hours in OGTT, insulin levels or HOMA-IR. In 15.8% of patients, diabetes mellitus was present, with a median duration of 1 year (range: 0.6 to 10 years), while 30.7% had prediabetes defined according to the American Diabetes Association . The medp = 0.104 and 0.606 ± 0.090 vs. 0.580 ± 0.126, p = 0.474, respectively). When looking independently at levels of total cholesterol, HDL, LDL and triglycerides, mean CIMT significantly correlated with total cholesterol and triglyceride levels. Dyslipidaemia was present in 42.4% of patients, but the groups divided according to the presence of dyslipidemia, or according to the use of statins did not show statistically significant differences in mean CIMT values . Among the whole group, 22.1% were current smokers. The comparison between the smoking and non-smoking groups showed no difference in mean CIMT values .A weak correlation between the patients’ ASCVD risk and CIMT values was found, while there was a significant positive correlation between ASCVD risk and SCORE , fasting glucose, total cholesterol, triglycerides, WHR, waist circumference, body muscle mass and SMI, which is consistent with the currently available relevant body of literature. Although our study group was significantly older according to vascular age relative to chronological age, no statistically significant difference in CIMT was noted when the mean measured values were compared with the expected normal age- and gender-adjusted values. The ASCVD risk assessment showed a significant positive correlation between the patients’ ASCVD risk and SCORE, but only a weak correlation of ASCVD with CIMT.Whether increased CIMT in the different populations investigated is due to intimal or medial thickening remains an open question. The answer can probably be determined with more sophisticated and detailed techniques, such as high-frequency ultrasound, which could be used to determine the exact pattern of changes in the arterial wall. In conclusion, since no diagnostic tool currently includes body weight as an individual risk factor, further trials are highly necessary to determine if SCORE, SCORE2, ASCVD risk assessment or CIMT would be the most accurate and relevant diagnostic tool for the prediction of risk for future CV events in patients with obesity because none of these diagnostic tools include body weight as a risk factor.


Chronic kidney disease (CKD) is an escalating medical and socioeconomic problem worldwide. Information concerning the causes of CKD, which is a prerequisite for reducing the disease burden, is sparse in Malaysia. Therefore, this study aimed to evaluate the attributable causes of CKD in an adult population at a tertiary referral hospital. Retrospective study at Hospital Universiti Sains Malaysia (HUSM).  This was an analysis based on medical records of adult patients at HUSM. Data regarding demographics, laboratory investigations, attributable causes and CKD stage were gathered. A total of 851 eligible cases were included. The patients' mean age was 61.18 ± 13.37 years. CKD stage V was found in 333 cases (39.1%) whereas stages IV, IIIb, IIIa, and II were seen in 240 (28.2%), 186 (21.9%), 74 (8.7%) and 18 (2.1%), respectively. The percentage of CKD stage V patients receiving renal replacement therapy was 15.6%. The foremost attributable causes of CKD were diabetic nephropathy (DN) (44.9%), hypertension (HPT) (24.2%) and obstructive uropathy (9.2%). The difference in the prevalence of CKD due to DN, HPT and glomerulonephritis between patients ≤ 50 and > 50 years old was statistically significant. Our results suggest that DN and HPT are the major attributable causes of CKD among patients at a Malaysian tertiary-care hospital. Furthermore, the results draw attention to the possibility that greater emphasis on primary prevention of diabetes and hypertension will have a great impact on reduction of hospital admissions due to CKD in Malaysia. Chronic kidney disease (CKD) is an overwhelming health and socioeconomic problem across the globe. Statistics from the United States suggest that for each patient with end-stage renal disease (ESRD), there are more than 200 with overt CKD (stages III or IV) and nearly 5000 with covert disease (stages I or II).Deplorably, this sort of evidence is sparse for developing countries, including Malaysia, where the estimated prevalence of CKD is around 9%In one descriptive study by Shaza et al.,We aimed to describe the demographics, clinical profile and possible attributable causes of CKD among adult patients at a tertiary-care hospital in Malaysia.A retrospective study based on the medical records of adult patients was conducted at Hospital Universiti Sains Malaysia (HUSM), Kota Bharu, Malaysia, which is a tertiary referral institute located in the state capital of Kelantan. This state has an estimated population of 1.68 million .Permission to conduct this study was acquired from the Human Research Ethics Review Committee, Universiti Sains Malaysia. Medical records (paper-based records) of adult patients (age ≥ 18 years) either seen in the CKD Resource Centre or admitted to HUSM due to CKD, between January 2009 and December 2013, were eligible for inclusion in the study. Medical records relating to patients with acute kidney injury, patients with acute deterioration on chronic kidney disease with insufficient information to confirm the attributable cause and/or stage of CKD and patients aged < 18 years were excluded. The researcher extracted the data from the medical records between January and May 2014. An average of 20 medical files were reviewed per day and information regarding demographics, laboratory findings, patient's medical history, family history of diseases, ultrasound or X-ray results relating to kidney, ureter and bladder (KUB), chest radiograph results, types of renal replacement therapy and probable cause of the disease were gathered.The attributable causes of CKD were assessed using the diagnosis that had been made by the nephrologist or clinician. If this was unavailable, the criteria described below were used to determine the probable cause of CKD.DN was considered to be the underlying cause of CKD if a patient had a confirmed diagnosis of diabetes mellitus (DM) and any of the following criteria: long-standing DM before the onset of CKD (minimum 10 years), evidence of substantial proteinuria, presence of diabetic retinopathy and normal-sized kidneys on ultrasound.HPT was diagnosed as a cause of CKD if a patient had any of the following conditions: long history of hypertension predating renal impairment (minimum of five years), presence of left ventricular hypertrophy or hypertensive retinopathy and no substantiation of any other etiology of kidney disease.Patients with chronic renal failure who had pathological proteinuria and normal or small kidneys and who ultimately developed end-stage renal disease (ESRD) with small kidneys were categorized as cases of chronic glomerulonephritis, whether or not a biopsy had been obtained.The procedures used for diagnosing obstructive uropathy (OBS) were KUB ultrasound, KUB radiography, cystoscopy, intravenous pyelography, retrograde pyelography and radioisotope renography. This diagnosis was made if the patient had solid evidence of urinary obstruction , with or without hematuria and presence of hydronephrosis and hydroureter.Chronic pyelonephritis (CPN) was considered to be the possible underlying etiology of CKD if a patient had a history of recurrent or persistent urinary tract infections and noticeable renal scarring.The diagnosis of adult polycystic kidney disease (APKD) was made if a patient had enlarged or palpable kidneys with bilateral complex renal cysts, with or without a family history of polycystic kidney disease and a history of flank pain.Toxic nephropathy was considered to be the presumptive cause of CKD if a patient had a strong history of use of nephrotoxic agents , traditional medicines etc.) and in the absence of indicators of any other etiology of kidney disease.Patients who were diagnosed with or presented CKD for the first time, for which no apparent cause could be found, were categorized as having disease of unknown cause. Other attributable causes were diagnosed on the basis of kidney imaging, renal Doppler ultrasonography, renal angiography and renal biopsy results.The CKD was classified based on the estimated glomerular filtration rate (GFR) as per the Kidney Disease Improving Global Outcomes (KDIGO) guidelines.The data are presented as mean ± standard deviation (SD) for continuous variables and numbers and/or percentages for categorical variables. The data were analyzed according to age groups (≤ 50 or > 50 years of age) and gender. Comparisons of categorical and continuous variables were assessed by means of the chi-square test and t test, respectively. Variables that were not available for a large proportion of the sample were not included in the final analysis. The analyses were carried out by using the Statistical Package for the Social Sciences  for Windows. A Pvalue < 0.05 was considered statistically significant.2, as calculated using the CKD-EPI equation. Using the KDIGO classification for CKD staging, we found that our patients were predominantly in the late stages of CKD (stages IV and V).The total numbers of patients admitted to and visiting HUSM during 2009-2013 are shown in The majority of the patients were asymptomatic. However, the chief complaints at presentation were nausea (20.9%), vomiting (15.3%), lethargy (52.6%), malaise (52.9%), edema (36.1%), poor appetite (50.3%), weight loss (11.6%), dyspnea (34.7%), decreased urine output/oliguria (10.8%) and dysuria (5.1%). The most frequent attributable cause of CKD was DN (44.9%), followed by HPT (24.2%) and OBS (9.2%), as shown in There was a substantial statistical difference in the prevalence of CKD due to DN between younger patients and older patients . Similarly, the difference in prevalence of CKD due to GN and HPT between the younger and older age groups was statistically significant . The differences in the prevalence of CKD between male and female patients, due to DN , APKD  and unknown cause , were also statistically significant.The attributable causes of CKD in the urban and rural zones are depicted in Renal replacement therapy, consisting of either hemodialysis (HD) or peritoneal dialysis (PD), was used in 134 patients (15.6%). Among these patients, HD was the most frequent type of treatment (93.3%), while continuous ambulatory PD was used much less frequently (6.7%). None of the patients received continuous cycling peritoneal dialysis or kidney transplants. In our centre, the majority of the patients decide themselves which type of renal replacement therapy they want. To help these patients to decide, pre-dialysis talks are held at the Chronic Kidney Disease Resource Centre, Hospital Universiti Sains Malaysia. After patients acquire all the information about types of renal replacement therapy, they choose their treatment. Patients who are interested in kidney transplantation are referred to Hospital Kuala Lumpur.Our main results showed that most of the patients with CKD in the sample were men and older people with advanced chronic kidney disease (stages IV and V). Beyond that, the most frequent attributable causes of CKD in the sample were DN and HPT. The mean age of the patients in the present study was similar to that of previous reports.Regarding the preferred types of dialysis, PD is the favorite treatment method in MexicoDN was the foremost attributable cause of CKD in our study population, and this finding is similar to previous reports regarding the causes of CKD (stages III to V).DN and HPT were the leading contributors towards CKD in the older age category . The differences in the frequencies of CKD due to DN and HPT between the younger and older age groups were statistically significant, and this finding was comparable to the results from another study conducted in an Asian country.Although we achieved the desired objectives of our study, it had some limitations. Firstly, this study was conducted in a single tertiary referral hospital in the northeast of the Malaysian peninsula and only 2.2% of the patients were from outside the northeastern region. Therefore, our results may not give a clear picture of attributable causes of CKD throughout Malaysia. Secondly, due to the predominance of the Malay ethnic group, the findings of this study cannot be generalized to the overall Malaysian population. Thirdly, due to the retrospective nature of this study, some data were not fully available: for example, income status, health-seeking behavioral patterns, distance to the healthcare facility and ability to afford transportation. However, this may not have significantly influenced the results. Lastly, we did not use a probability sampling method, e.g. random sampling, and therefore we had disadvantages such as selection bias and non-generalizability.This study recommends that emphasis is required at two levels: firstly, identification of individuals at risk of CKD development or presenting early CKD, as soon as possible; and secondly, early referral of CKD patients to nephrology centers by primary care physicians. This second approach has already demonstrated improvements in treatment outcomes, and it results in earlier preparation of the start of dialysis.The data suggest that DN and HPT are the major attributable causes of Chronic Kidney Disease among patients at a tertiary referral hospital in the northeast of the Malaysian peninsula. Although the results cannot be easily generalized to the general population, the study draws attention to the possibility that greater emphasis on primary prevention of diabetes and hypertension will have a large impact on reduction of hospital admissions due to CKD in Malaysia.


Pbcn BiN (S.G. #60) from Bi and N2 precursors at pressures above 40 GPa. Using synchrotron single-crystal X-ray diffraction on the polycrystalline sample, we solved and refined the compound’s structure and studied its behavior and compressibility on decompression to ambient pressure. We confirm the stability of Pbcn BiN to pressures as low as 12.5(4) GPa. Below that pressure value, a group–subgroup phase transformation occurs, resulting in the formation of a non-centrosymmetric BiN solid with a space group Pca21 (S.G. #29). We use ab initio calculations to characterize the polymorphs of BiN. They also provide support and explanation for our experimental observations, in particular those corresponding to peculiar Bi–N bond evolution under pressure, resulting in a change in the coordination numbers of Bi and N as a function of pressure within the explored stability field of Pbcn BiN.We explore chemical reactions within pnictogens with an example of bismuth and nitrogen under extreme conditions. Understanding chemical reactions between Bi and N, elements representing the first and the last stable elements of the nitrogen group, and the physical properties of their compounds under ambient and high pressure is far from being complete. Here, we report the high-pressure high-temperature synthesis of orthorhombic  Theoretical and experimental studies under extreme conditions have recently rejuvenated the interest in the chemistry of pnictogens and their compounds . Each ofUnlike the unhealthier high-Z counterparts of the pnictogen group , Bi has very low toxicity for a heavy Z element. It reacts with oxygen, sulfur, and halogens, but at the same time, it is somewhat reluctant to form stable compounds with carbon  and nitr3 and NH3 at ambient pressure, here, we report the synthesis of the BiN compound, obtained by compressing the Bi and N2 precursors to high-pressure conditions and laser heating. In the following paragraphs, we present a description of our experiments up to 50 GPa and discuss the experimentally determined structure of BiN, its striking evolution under stress and decompression. At last, but not the least, we compare our experimental observations with the results of our ab initio calculations.In contrast to Franklin, who first synthesized BiN through a reaction between BiBrBeing discovered more than a century ago, BiN has been a challenge for chemists and material scientists. From 3. Molecular nitrogen gas was loaded at pressures of 1.4–1.5 kbar into the sample chamber using the P02.2 beamline’s high-pressure gas loader  to confirm full quenching to ambient conditions. The temperatures achieved by laser heating were measured by means of spectral radiometry  by means of compound refractive lenses  or Kirkpatrick–Baez mirrors . Each synthesis attempt was followed by a 2D mapping of the heated area, revealing the most promising sample positions for a subsequent multi-grain single-crystal data collection. The latter data were acquired with a step of 0.5° during a continuous rotation of ±30° along the ω rotation axis.X-ray diffraction patterns were recorded using the Perkin Elmer XRD1621 detector of P02.2 with the sample illuminated by an incident X-ray beam with a wavelength of either 0.4839, 0.2904, or 0.2909 Å (depending on the experiment) focused down to either 0.9∙0.9 or 2∙2 μmPRO  and “N” (ENMAX = 400 eV) PAW potentials with valence configurations of 6s25d106p3 for Bi and 2s22p3 for N were used. For the sake of clarity, here and in the following paragraphs, when necessary, we will use the superscript VdW, indicating results obtained by (A2). We employed the Monkhorst–Pack scheme with 8 × 4×4 for Pbcn-BiN or 4 × 8×4 for Pca21-BiN k-points for Brillouin zone sampling, and the plane–wave kinetic energy cutoff was set to 800 eV, ensuring total energy convergence to better than 0.5 meV/atom. For electron band structure calculations, the two-fold denser k-point grids were used. The finite displacement method, as implemented in Phonopy , as implemented in the Vienna Ab initio Simulation Package (VASP) . The pro Phonopy , was use2 were made to pressures of up to 50 GPa through sample laser heating. The first synthesis attempts at pressures of 12–15 GPa and ∼30 GPa were unsuccessful. Indeed, although at these pressure ranges, laser heating to temperatures of ∼1800 (200) K resulted in bismuth melting, the collected X-ray diffraction data did not reveal any signs of a new phase being produced. However, upon further increasing the pressure to 42.5 (3) GPa and laser heating, new diffraction lines, suggestive of a chemical reaction and the formation of a novel compound, were observed. Although all synthesis attempts were conducted at high temperature, the data discussed here and in the following paragraphs were collected at room temperature. The analysis of the thereafter obtained single-crystal X-ray diffraction data enabled to unambiguously index the produced solid to have lattice parameters of a = 4.8941(5) Å, b = 9.4020(10) Å, and c = 9.176(4) Å, and the Pbcn space group (S.G. #60). The R-factors of the best solution are as follows: Rint= 2.5% and R1 = 2.6% for I > 2σ(I), with I and σ being the integrated intensity and its standard deviation value, respectively. More information on the single-crystal data, along with the tables containing the crystallographic parameters for this and other pressure points, is shown in Attempts to obtain a chemical reaction between pure Bi and NPbcn BiN is constituted of four crystallographically independent atoms, two Bi atoms (Bi1 and Bi2) and two N atoms (N1 and N2)  . The Bi1Cmce, bp-N)  , where ePbcn BiN with cubic gauche polymeric nitrogen   ° to 112.6 (4)°. At the same time with Pbcn BiN, at a pressure of 42.5 (3) GPa, the Bi–N1–Bi angles have values of 98.8 (6)°, 105.1 (6)°, and 108.3 (4)°, while the values of Bi–N2–Bi angles are 94.2 (6)°, 102.4 (7)°, and 105.6 (4)°. Some of these angles are somewhat smaller than the reference angles of 108.8 (3)° in cg-N (115.4 GPa) (bp-N (140 GPa)   and cubiG. #198) . The syn5.4 GPa)  and 105.140 GPa) . This evone pair .Pbcn BiN, Bi should have three single bonds with N (sp3 hybridization), and as we will show in the upcoming section, this should hold true for Bi1 for Pbcn BiN below 50 GPa, but the situation for Bi2 requires an additional discussion and comparison with ab initio calculations. In addition to synthesizing Pbcn BiN at 42.5(3) GPa, we also successfully produced it at pressures of 47.4(2) GPa and 51(1) GPa. In all three syntheses, we could not find any other Bi–N compounds than Pbcn BiN. We also collected the data on decompression and report that upon quenching to 1 bar, Pbcn BiN undergoes a solid–solid phase transition toward a phase with the space group Pca21, presumably via a group–subgroup transformation. It is interesting to note that similar behavior is observed for δ-P3N5 (3N5 upon decompression below 7 GPa (C2/c → P21/c). The crystallographic details of Pca21 BiN are provided in the Pca21 in two separate different loadings: once by means of powder diffraction (the sample stabilized by an Ar atmosphere after being decompressed in a glovebox) and once by means of single-crystal diffraction and subsequent data analysis (the sample was carefully decompressed until the Raman shift of molecular nitrogen corresponded to ambient pressure). The R-factors of the best Pca21 solution are as follows: Rint = 1.4% and R1 = 2.9% for I > 2σ(I). Pca21 and Pbcn BiN side-by-side.Our observations indicate that in r δ-P3N5 , spontanPca21 and Pbcn BiN shows that a loss of a symmetry element on decompression (Pbcn → Pca21= Pbc21) resulted in a significant structural reorganization. We obtain twice more independent Bi and N positions (Wyckoff sites 4a) without a change in formula units per unit cell . Considering the local nitrogen environment of Pca21 BiN and the Bi–N–Bi angles, we see a relatively narrow distribution of their values around 111° , with the smallest and the largest values being 100.9 (5)° and 114.6 (7)°, respectively. These values are in a closer agreement with the As–N–As angles reported for the cubic AsN  GPa. Unfortunately, we do not have experimental datapoints between 12.5(4) GPa and ambient pressure. Here, we performed conventional ab initio calculations investigating the stability of the discovered BiN polymorphs with and without the contribution of van der Waals forces. It was indicated by ab initio calculations strongly support the experimental observations with respect to the phase stability; Pca21 at 1 bar and for Pbcn at 49 GPa. At the same time, the enthalpy calculations, shown in Pca21 and Pbcn BiN polymorphs at lower and higher pressures, respectively (Pca21VdW) to 0.45 eV (PbcnVdW) if we consider 0 and 49 GPa, respectively. Both approximations employed in ab initio calculations confirmed the dynamical stability of the phases in their corresponding stability fields. The calculation including van der Waals forces provides better agreement with an experimental unit cell volume for Pca21 BiN. We did not see a considerable difference between the results produced by different approximations for the Pbcn phase. In the Concerning the stability of the individual ectively . The phoectively , and in ab initio predictions.The structural complexity of BiN finds a correlation with its peculiar compressibility, as shown in Pbcn BiN at pressures above 35–38 GPa. Indeed, within the pressure range of 40–50 GPa, the volume of the unit cell does not change much. This peculiar behavior correlates with our observation of a strongly reduced compound volume compressibility, as confirmed in three different loadings and syntheses. We note that although nitrogen is far from being a perfect hydrostatic medium, laser heating tends to anneal undesirable deviatoric stress effects and micro-strains  seems to overestimate the experimental data at pressures below ∼47 GPa. The overestimation of the lattice parameters and unit cell volume in DFT-relaxed structures is known for other Bi-bearing compounds  Å3, K0 = 64(19) GPa, and K’ = 5.6(9), where the parameters correspond to the ambient pressure volume, isothermal bulk modulus at ambient pressure, and its pressure derivative. The theoretical K0 value is low, which is expected from a Bi-bearing compound  and those omitting them (A1), respectively. This contrast likely indicates a greater role of the forces for interatomic interactions within the lower pressure Pca21 phase. Our calculations for Pbcn propose the suppression of van der Waals forces at higher pressures. Altogether, although our conventional calculations may not be perfect, we will show that they capture essential aspects of Pbcn BiN and the evolution of its crystal chemistry.If we look at the bulk compressibility, the ompounds  and attrgham EoS  obtainedcompound . The calPbcn BiN, both the theory and the experiment qualitatively agree with respect to the Bi1-N and Bi2-N distances and to the Bi1 and Bi2 coordination number change under stress. Bi1 has three shortest bonds , the corresponding coordination number CNBi1 = 3, and this situation does not change at different pressures. In contrast, the connectivity of Bi2 is different and does vary as a function of pressure. At ∼12.5(4) GPa, we observe two short Bi2-N bonds with lengths comparable to Bi1-N and two bonds of larger intermediate length (∼2.5–2.6 Å). The latter are illustrated using dashed ellipses in Bi2 = 4, but at higher pressures, the network is rearranged with the shortest Bi2–N bonds (below 2.35 Å) being enclosed within the Bi–N layers and resulting in CNBi2 = 3 at 51.0(5) GPa. Additional graphical information comparing the unusual Bi near neighbor coordination at pressure points of 12.5(4) and 51.0(5) GPa is presented in the Pca21, we observe CN = 3 for all atoms.As shown in Bi2 = 4 in Pbcn BiN is highly peculiar, and it is supported by both our experiment and calculations. It implies the same coordination number CNN2 = 4 for nitrogen occupying position N2 at 12.5(4) GPa and directs to a general discussion of the nitrogen strength as an electron acceptor in inorganic compounds and bonding type. Calculated Bader charges for BiN at 12.5(4) GPa  and electron localization function calculations (We emphasize that the observation of CNulations  demonstrulations .Bi2 = CNN2 = 4 between Pca21 and Pbcn phases if we think of the structures at the pressures of 0 GPa (CNBi = 3) and 51.0(5) GPa (CNBi = 3), respectively. A review of the literature will show various examples with the coordination number strictly increasing as a function of pressure  to Pbcn BiN and also exhibits thermoelectricity  at 1 bar and CN = 3 (Pbcn BiN) at 40–50 GPa. We consider that the change in the coordination number related to the Bi–N bond rearrangement could be responsible for the observation of the BiN reduction of compressibility in the pressure range of 40–50 GPa.Our results on the BiN compressibility revealed a region with an anomalous behavior of lattice parameters and unit cell volume as a function of pressure. After comparing the experimental results with the results of Pca21 and Pbcn BiN). We show that a conventional calculation approach is capable of uncovering important evidence but may not be fully sufficient to expose all the details of complex material behavior. Recent advances in the field of ab initio calculations are admirable, but many sophisticated techniques still have limited distribution due to limited access to the computational resources and extended duration of calculation. Improved accessibility to techniques like the continuous-time strong-coupling quantum Monte Carlo method coupled with state-of-the-art experimentation will considerably shorten the path between a synthesis discovery and a potential practical application. However, this is work for the future.Our study is one of many indicating the computational challenge for materials incorporating a significant concentration of heavy elements along with a large number of formula units per unit cell (e.g., Z = 16 for The case of BiN is special because this compound is formed from stable elements of the pnictogen group, with the highest contrast between constituents in terms of electron per group element. To the best of our knowledge, this is the first study investigating the crystal chemistry of BiN at ambient and extreme conditions. The reported findings are intriguing and expand our understanding of metal–nitrogen crystal chemistry in general and our knowledge of inter-pnictogen reactions in particular.


In this study, an attempt was made to investigate the distribution of coronary risk factors in male patients with coronary artery disease (CAD)(n=50 each) belonging to Jaat and Vaishya castes. A Significantly higher average height, waist and hip circumferences,glucose, and waist-height ratio were observed in Jaats compared to the Vaishyas (p=0.000). Mean BMI, total cholesterol  and non-high density lipoprotein cholesterol (HDL-C), and lean body mass index (LBMI) were significantly higher in Vaishyas againstJaats (p=0.00). A significantly higher percentage of type 2 diabetes(T2DM) (p=0.03) and isolated hypertriglyceridemia(p=0.01) was observed in Jaats against Vaishya men. Percentage of general obesity(p=0.01), high total-C, high low density lipoprotein cholesterol(LDL-C) (p=0.00), high total-C/HDL-C(p=0.04), combined positive family history of hypertension and type 2 diabetes, and general obesity, was significantly higher in Vaishya when compared to Jaat men. In univariate logistic regression analyses, a significantassociation of T2DM (p=0.039) and isolated hypertriglyceridemia (p=0.020) with Jaat ethnic group and general obesity, high totalC, high LDL-C, and high total-C/HDL-C with Vaishya ethnic group was observed. Results of the present study suggest that apopulation-specific than a global approach should be used in identifying high-risk groups and designing of interventions to reduce the complications and management of CAD. Analysis of the global burden disease dataset from 1990-2016 revealed that 126 million or 1.72% world's population were affected by CAD and responsible for nine million global deaths . Risk faThe estimated sample size required for the study was 50 for two caste populations each when the following assumptions were made: (1) α= 0.05, (2) β= 0.20, (3) mean difference= 8, (4) standard deviation = 14 in two endogamous groups and (5) the number ofcases in two endogamous groups are equal.Newly diagnosed CAD patients aged >20 years.Those who were in critical condition and unwilling were excluded.Patients of CAD (n=50) each belonging to Jaat and Vaishya were recruited in the study following inclusion and exclusion criteria when patients were transferred to intermediate care units of departments of Cardiology of Asian Institute of Medical Sciencesand the Fortis Escort hospital Faridabad, Haryana.CAD was diagnosed based on the angiogram, elevated serum creatine kinase (MB) and electrocardiogram by the cardiologists of the respective hospitals. Data on age, marital status, type of family, education, occupation, income, physical activity, tobaccochewing, alcohol intake, positive family history of CAD and other diseases were enquired from the patients and documented. Socio-economic status of the patients was categorized using the modified KuppuSwamy scale (2021). After inquiring the patients, physicalactivity was categorized into no, occasional and regular activity. Height was measured on minimal clothing using anthropometer and weight on minimal clothing by calibrated electronic weighing machine. Body mass index (BMI) was calculated using the formula(weight in Kg/ height in meters2). Those patients exceeding BMI values >25 were considered obese. Waist circumference (WC) was measured mid-way between the inferior margin of the last rib and the crest of the ileum in horizontal plane and hipcircumference taken at the point of maximal protrusion of buttocks while the patient was standing with his feet close to each other, employing plastic tape. Waist-hip ratio (WHR) was calculated using the formula (waist circumference /hip circumference).Those patients having WHR ratio of 0.9 and WC >90 centimetres were categorized as centrally obese. Blood pressure was recorded using manual Mercury sphygmomanometer. Patients with systolic blood pressure (SBP >140mmHg) and diastolic blood pressure (DBP)>90 mmHg or/and on medication for hypertension were labelled as hypertensive. A 5 mL anticoagulated non-fasting blood sample was drawn from the patients and plasma glucose, total-C, HDL-C, triglyceride and LDL-C levels were estimated using enzymatickits on Roche autoanalyzer model COBAS integra 400 plus. Those patients with random glucose level of >200mg/dl were labelled as T2DM. CAD patients were classified into different groups using the following criteria: High total-C(>200mg/dl),high triglyceride(>150mg/dl), high LDL-C(>130mg/dl), low HDL-C(<40mg/dl), High LDL-C/HDL-C (>3.5), high total-C/HDL-C(>4.5), isolated hypercholesterolemia, isolated hypertriglyceridemia, isolated low HDL cholesterol  and dyslipidemia .Averages of continuous variables between Jaats and Vaishya were compared to know the significant differences and the results are presented in Studies on the prevalence of coronary risk factors (CRFs) in CAD patients of different ethnic groups  and 12, Significant differences in the distribution of coronary risk factors as well as the components of risk factors  were observed between CAD patients of ethnic groups in the present study. Within each ethnic group clustering of coronary riskfactors was found to be different and also the effect of qualitative categorical variables on the quantitative variables. Population-specificapproach of identifying high-risk groups and designing of interventions may yield good results in reducing thecomplications and management of CAD. Case-control studies in ethnic groups may enlighten us on the strength of association between coronary risk factors and CAD which are in progress.


People experiencing homelessness have an increased risk of mortality. The association between being at risk of homelessness and premature mortality is unclear. We aimed to determine all-cause and cause-specific mortality in patients who were homeless, at risk of homelessness , or housed.This retrospective longitudinal cohort study compared mortality patterns in adult patients identified in 2003/04 by linking data from an Australian metropolitan emergency department to national mortality data. We used Cox proportional hazards models to estimate associations between housing status and mortality. To address competing risks, cause-specific hazards were modelled and transformed into stacked cumulative incidence functions.Data from 6290 patients  found increased risk of mortality in homeless [hazard ratio (HR) = 4.0, 95% confidence interval (CI) = 2.0–3.3) and marginally housed  patients. Homeless patients had an excess risk from external causes , cardiovascular disease  and cancer . Marginally housed patients had increased risk from external causes  and respiratory diseases . Taking account of competing risk, marked inequality was observed, with homeless, marginally housed and housed patients having probabilities of death by 55 years of 0.2, 0.1 and 0.02, respectively.Mortality rates were elevated in patients who were homeless or at risk of homelessness. Increasing numbers of people are at risk of homelessness, and the effect of this on mortality is relatively unrecognized. Marginal housing may assuage some risk of premature mortality associated with homelessness; however, it is not equivalent to stable housing. Key MessagesThis study tests the associations of experiencing homelessness or being at risk of homelessness  with mortality, using patient data linked to a national mortality database.Both the homeless and the at risk of homelessness experiences were associated with an increased risk of mortality.Detailing all-cause and cause-specific mortality in patients who are at risk of homelessness fills a gap in the literature and is a novel contribution.Marginal housing may lessen some risk of premature mortality associated with homelessness; however, it is not equivalent to appropriate, stable housing.,,The prevalence of homelessness is increasing in most high-income countries.,Marginal housing is rented accommodation, below minimum standards, associated with government support and frequently tenuous. People in marginal housing are at risk of homelessness.This retrospective, longitudinal, cohort study analysed data from patients attending an ED in a 540-bed, inner-city, tertiary hospital between 1 January 2003 and 31 December 2004, who were identified as homeless or marginally housed. The ED is proximal to homeless communities and social housing complexes and is renowned for its care of people experiencing homelessness. Patient data were linked to national death records through January 2020 by the Australian Institute for Health and Welfare (AIHW).,,IJE online) for definitions of housing classification, including inter-rater reliability data.Consistent with prior studies,n = 39 528), was selected as a comparison group in a 3:1 ratio to the exposed group .A random sample of ED patients without a documented history of homelessness/marginal housing (i.e. ‘housed’), who presented at least once in 2003/04  compiles death registrations in Australia. It contains person-level records, including facts  and cause(s) of death [i.e. up to 14 causes of death mapped to the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10)  and the primary cause plus other causes listed were considered .The cohort was described using frequencies/percentages and medians/interquartile ranges. Patient characteristics were compared using Fisher’s exact test for categorical variables and Wilcoxon rank sum or Kruskal–Wallis tests for continuous variables.P <0.05).Given the epidemiological nature of our study and left truncation of the data, we chose age as the time scale.Competing risks are a common occurrence in survival analysis and arise when a patient is at risk of more than one mutually exclusive event, such as death from different causes.An unadjusted Cox proportional hazards model estimated the associations between housing status index and all-cause and cause-specific mortality, including alcohol and drugs separately. Hazard ratios (HRs) and 95% confidence intervals (CIs) were generated for homeless and marginally housed patients, with housed patients as the reference category. We assessed for violations of the proportionality assumption by calculating Schoenfeld residuals. If proportionality did not hold, flexible non-proportional parametric models were created using restricted cubic splines to incorporate time-dependent effects.IJE online). Homeless and marginally housed patients were more likely to be male, born in Australia and to identify as Aboriginal and/or Torres Strait Islander compared with housed patients . KM survival curves demonstrated a gradient in age at death by housing status (The median age of death was younger in homeless (57 years) and marginally housed patients (73 years) compared with housed patients  and marginally housed  patients after their index (first) 2003/04 ED presentation, compared with housed patients who presented for ED care during the same period .The stacked CIF visualizes the total probability of death by age and the contribution each cause makes to this probability . These gThe leading causes of death among homeless patients were external (24.8%), CVD (21.3%) and cancer (14.7%), and among marginally housed patients they were CVD (25.9%), cancer (19.1%) and external causes and respiratory diseases , CVD and cancer, replicating international studies.Taking account of competing risk, marked inequality in the probability of death was observed between the three groups at similar ages. To contextualize this finding, the probability of a homeless patient in this study dying at age 55 years would be equivalent to a male dying at age 72 and a female at age 77 in the general population in Australia.,External causes accounted for nearly 25% of deaths in homeless patients and 12% in marginally housed patients. Comparable studies conducted in England and Canada found similar rates of deaths due to external causes among patients who were homeless (22–27%).,Deaths due to alcohol consumption included both acute  and chronic effects  and were more common in homeless patients (10%) than in marginally housed (5.6%) and housed patients (1.3%). Finding elevated alcohol-related deaths among homeless patients was not surprising, given that alcohol use disorders are the most common diagnoses among people who experience homelessness.In the current study, the proportion of deaths directly caused by drugs was higher than that due to alcohol across all three groups. Similar rates of death due to drug overdose have been reported in homeless populations in the USA .et al., coupled with our focus on patients who presented for ED care (as opposed to the broader homeless population) who may have poorer health. Al-Shakarchi et al.Death due to CVD was common to all three groups in this study, but homeless patients’ median age at death from CVD was almost 20 years lower than the corresponding ages for marginally housed and housed patients . Furthermore, the risk of a patient with a history of homelessness dying from CVD was almost five times that of a housed patient. A recent systematic review found the risk of premature mortality from CVD in people experiencing homelessness was three times that in housed populations.We found similar risk for a CVD death in marginally housed and housed patients. It is possible that the unique challenges that contribute to the high burden of CVD among homeless patients may be lower among marginally housed individuals. Indeed, prior research has shown that moving into housing is associated with significant reductions in use of emergency medical services.,,Death from respiratory disease was more common in marginally housed patients; with a higher incidence of chronic obstructive pulmonary disease (COPD), they were 4.7 times as likely to die from respiratory disease as housed patients. It is possible that those who are marginally housed are at greater risk of respiratory disease given its higher prevalence in poorer socioeconomic areaset al.Previous research has reported findings similar to those in the present study of higher than anticipated mortality in formerly homeless people.et al.,These findings indicate that being marginally housed may assuage some risks of premature mortality associated with homelessness; however, marginal housing is not equivalent to being appropriately and stably housed. The mortality disparity between marginally housed and housed patients in this study may be the consequence of health inequalities associated with low income, the sequelae of previous homelessness, as suggested by Tsai Strengths of this study include the detailed examination of medical records to determine housing status, a high number of cases and the use of national mortality data. Sophisticated analysis to ascertain the risk of mortality by housing status, moving beyond standard Cox regression to apply flexible modelling that incorporated time-dependent effects, enabled survival analysis over 16 years—a first in literature on mortality among people who experience homelessness. Similar mortality outcomes reported in the present and international studies add to the evidence documenting housing as a social determinant of health and advances the literature by demonstrating similar findings in a sample of marginally housed patients. Further, detailing all-cause and cause-specific mortality in patients who are at risk of homelessness fills a gap in the literature and is a novel contribution of this study.Several limitations warrant mention. Individuals who were homeless were identified via medical record chart review. Underestimation of homelessness/marginal housing may have occurred due to a reliance on patient self-report of usual accommodation. Although this challenge is inherent when using routinely collected health data, it was mitigated by skilled examination of individual medical records by a member of the research team. Additionally, the definition used for marginal housing, commonly used in the Australian context, may not be transferable to other national contexts.Ascertainment of homelessness occurred over a 24-month period and housing trajectories were not tracked thereafter. Thus, we do not have data on whether patients’ housing status changed or remained the same over 2005–20. It is possible that individuals who exit homelessness have reduced mortality rates, and the possibility that mortality among that group was overestimated should be considered. Alternatively, the accommodation status of marginally housed and housed patients may have deteriorated following the study enrolment period, potentially leading to mortality associated with housing status to be underestimated in those groups. Deaths due to cardiovascular and respiratory diseases and cancer among homeless and marginally housed patients may be explained, in part, by smoking. The prevalence of smoking in homeless populations ranges between 57% and 82% and is well above that of general populations.This is the first study to move beyond all-cause mortality to quantify premature mortality risk and causes of death among ED patients who were homeless and marginally housed. This long-term analysis demonstrates persistent health inequalities among housed, marginally housed and homeless patients. Compared with patients who sought ED care who were housed, the homeless and marginally housed patients died 22 and 6 years younger on average, respectively. Our findings suggest that being homeless or marginally housed at a single point in time is a risk factor for long-term premature mortality.Approval was obtained from St Vincent’s Hospital, Melbourne (HREC/18/SVHM/236) and the Australian Institute for Health and Welfare (EO2019/3/1072) human research ethics committees.dyad006_Supplementary_DataClick here for additional data file.