Diverticulosis is not well characterized in the Caribbeans. Our aim was to compare the anatomical presentation of colonic diverticulosis in African Caribbeans (group AC) versus Europeans (group E) and severity.  We conducted a prospective controlled study involving 274 patients admitted for lower gastrointestinal haemorrhage (LGIH) in France ; 179 cases with diverticular haemorrhage, including 129 in group AC and 40 in group E. Exploration of the colon included a detailed assessment of diverticula using a dedicated endoscopic grid. p=0.01) during hospitalization. Out of the 169 patients included in the study, a complete exploration of the colon was achieved in 81% (N = 137) , and revealed right-side diverticulosis in AC  and left-side diverticulosis in E . These data were confirmed by a sensitivity analysis using an endoscopic grid in 92 patients, achieving a higher frequency and larger size of diverticula in AC.  AC and E had similar characteristics in terms of age, gender, previous history of LGIH, body mass index, dietary habits, and medications, but AC had significantly poorer hemodynamic parameters at admission and required more blood transfusions (66.7% vs. 42.5%;  Our study has shown that diverticulosis was pancolonic in AC and more frequently associated with more severe haemorrhage than the left-sided diverticulosis of Europeans. This anatomical presentation may be driven by the genetic background more than the environment and diet. There are considerable geographic variations in the prevalence of colonic diverticular disease (DD). It is common in Western countries, with an estimated prevalence that ranges from 45%  to 60% iSeveral factors have been associated with an increased risk of DD and its complications, including advanced age, gender, obesity, and dietary fiber intake , 14–17. The diverticular disease remains mainly asymptomatic; however, in 25% of individuals, it will develop as a symptomatic disease. The pathogenesis of symptomatic and complicated DD remains uncertain but involves at least in part, genetic predisposition, low-grade inflammation, altered intestinal microbiota, visceral hypersensitivity, and abnormal colonic motility .Preliminary data supported that ethnicity and genetic background may be implicated in the anatomical distribution and presentation of colonic DD . DivertiThe present study was performed prospectively in a Caribbean population and involved a control group of Europeans. To better characterize the role of ethnicity and people migration in DD, the comparison of African Caribbeans to Europeans, because they are exposed to a similar environment , could be useful.The aim was to compare the anatomical presentation as the first endpoint and the severity of colonic DD as the secondary endpoint, both as a function of the ethnic group. Moreover, a dedicated endoscopic grid was used to obtain precise insights into DD.This noninterventional study was conducted prospectively in the gastroenterology departments at the University Hospital of Guadeloupe (center 1) and La Roche-sur-Yon Regional Hospital, Vendée (center 2), two tertiary referral centers for gastrointestinal bleeding . Center Eligible patients were screened between March 9, 2013, and March 9, 2015, during which they were admitted for lower gastrointestinal hemorrhage (LGIH); this was defined as rectal bleeding and a normal upper endoscopy if the hemoglobin level was lower than 10 g/dl at admission, or melena with normal upper endoscopic findings. The included patients were 18 years or with a diagnosis of diverticular hemorrhage (DH), defined as (1) presumptive if colonic diverticula were present and no other obvious lesions could explain the bleeding or (2) definitive because active bleeding, an adherent clot, or a nonbleeding visible vessel was observed from diverticula . They unDuring the colonoscopy, a senior endoscopist (with more than 5 years of experience) completed a detailed endoscopic grid, which reported the size and number of diverticula in each colonic segment . The distribution of diverticula in the colon was assigned to one of four conventional categories for the disease according to the classification developed by Golder et al. : left-siA CT scan was performed in patients with a hemoglobin level lower than 10 g/dl at admission. For those with a diagnosis already determined by a colonoscopy carried out within the past three years, the evaluation was considered to be complete and no additional colonoscopy was required. In the absence of these diagnostic criteria, a complete colonoscopy (satisfactory preparation and complete examination up to the cecum) was performed. For patients with an incomplete colonoscopy due to a technical failure or severe comorbidities contraindicating analgesia, exploration was completed by means of a CT scan.The CT scans were reinterpreted by two senior radiologists specialized in abdominal radiology at each center. These two senior radiologists, SD and PM, assessed the number of diverticula in each colonic segment according to the four-point graded scale used for the endoscopic grid. The size of the diverticula on the CT scan was defined as large when greater than 1 centimeter and giant when greater than 2 centimeters .Severe active hemorrhage was defined by a pulse rate higher than 100 bpm and/or a systolic arterial blood pressure lower than 90 mmHg and/or more than 6 units of packed red blood cells transfused during the same period of hospitalization in a context of persistent bleeding. The therapeutic strategy consisted of medical management with appropriate transfusion support and procoagulant agents associated with endoscopic hemostasis, when possible. Surgical colon resection of the diseased segment or subtotal colectomy was performed in case of more than 10 units of packed red blood cells transfused with a failure of endoscopic hemostasis.The following clinical and biological data were recorded at admission: age, gender, body mass index, comorbidities, past LGIH, use of anticoagulant, antiplatelet, or nonsteroidal anti-inflammatory drugs, type of bleeding , systolic and diastolic blood pressure, heart rate, hemoglobin level, platelet level, and prothrombin time. During hospitalization, the numbers of packed blood cell units and hemostatic endoscopic or surgical procedures were recorded. The average daily consumption of fruits, vegetables, and whole grain food was assessed following a qualitative dietary questionnaire prospectively completed by a dietitian during a face-to-face patient interview. This questionnaire assessed the frequency of fruits, vegetables, and whole grain foods  usually consumed per day, per week, or per month and was completed in the two centers. The starchy foods, a representative of carbohydrate intake, were also reported qualitatively and compared in the two populations, as starchy foods are quite popular in the Caribbean islands' eating habits.p values <0.05 were considered to be significant. All authors had access to the study data and reviewed and approved the final manuscript.The statistical analysis was performed using SAS software . Means and standard deviations were calculated for continuous variables, medians for skewed distributions of continuous variables, and proportions for categorical data. We determined the distribution of diverticula at the group level. Spearman's correlation was used to assess the association between participant characteristics and the distribution of diverticula by location. We estimated odds ratios and 95% confidence intervals using the nonparametric Mann–Whitney test for quantitative variables, while the chi-square test or Fisher's exact test was used for qualitative variables. All tests of significance were two-tailed, and Overall, 274 patients were screened for LGIH: 220 in center 1 and 54 in center 2 . Of themp=0.001). Median PT ratios and platelet counts did not differ between the two groups.Similar characteristics were found in groups AC and E with respect to age, gender, previous history of LGIH, body mass index, dietary habits, and the prescription of platelet aggregation inhibitors, oral or subcutaneous anticoagulants, antihypertensive, antidiabetic, or non-steroidal anti-inflammatory drugs . Vitaminp=0.02), a higher proportion of those with a high pulse rate , and a higher proportion of nadir hemoglobin rates lower than 8 g/dl  or those requiring blood transfusions  than Europeans.African Caribbeans had significantly lower systolic blood pressure values (117 (100–130) vs. 127 (110–138); p=0.19, in groups AC vs. E, respectively. Moreover, DH was treated endoscopically in three patients (2.33%) vs. 0 (0%), p=0.44, or surgically in eight patients (6.2%) vs. 1 (2.5%), p=0.32, respectively, and no radiological embolization procedures were performed. Surgical management consisted in one right hemicolectomy (CT scan with contrast blush), two left hemicolectomies, and five subtotal colectomies (severe hemorrhage without contrast blush) in group AC, vs. one left hemicolectomy in group E.Almost all patients were managed medically, i.e., 123 (95.4%) vs. 40 (100%), n = 67 during hospitalization, n = 17 during the three years before hospitalization) and 25 patients from group E (80.6%); or (2) a partial colonoscopy associated with a CT scan or virtual colonoscopy in 22 (20.8%) and 6 (19.4%) patients, respectively.As shown in p < 0.0001; including 73.6% vs. 35.5% pancolonic forms; p=0.0002, 8.5% vs. 3.2% isolated right-side DD; p=0.03, and 8.5% vs. 3.2% bipolar forms; p=0.03. Inversely, in group E, diverticula were localized in the left-side colon in 96.8% of patients, including isolated left-side DD  in the majority of cases , mainly included into pancolonic DD  in group AC and isolated left-side DD in group E . There was no difference in the presence and number of diverticula in the right-side and in the left one in AC, while Europeans were clearly characterized by left colon diverticula  or more than 100 diverticula in one segment  was significantly higher in group AC vs. group E (p=0.004).The number of patients with more than ten diverticula in the left colon  and third  generations of diverticula developed deeper in the colonic wall were observed  and the median classes of diverticula were also higher in African Caribbeans than Europeans, in both the right and left-sides of the colon. These data confirm a tendency toward a higher proportion of diverticula in the colon of African Caribbeans, whatever the segment.The risk of having a higher number of diverticula among African descent than Europeans was controversial between the two studies, according to the studies of Golder et al.  and PeerNumerous questions remain regarding the genesis of DD. Some studies have shown that changes to the colonic wall may affect the pathogenesis of colonic DD . ChangesNevertheless, it might be interesting to conduct a study on the structural characteristics of supportive connective tissue and their genetic background in populations from different ethnic groups.The clinical severity of DD has been evaluated in three retrospective studies that included 30 to 40 Africans, and DH was the most common complication (in more than 50%) –13. EstiOur study has shown a right-sided involvement and pancolonic forms of diverticula in African Caribbeans compared to the left-sided localization in Europeans, and particularly the greater endoscopic and clinical severity of DH in African Caribbeans. This particular presentation is probably related to the genetic background of their African ascendance as opposed to the environment. Patient management should be adapted to this particular presentation of DD in African Caribbeans, and the possibility of more frequent subtotal colectomies should be discussed in cases of severe hemorrhage. In view of the fact that DH occurs most frequently in elderly patients with comorbidities and multiple medications, it is now essential to determine specific prognostic markers for this condition.


Renovascular hypertension in most cases requires endovascular treatment and/or surgery. This is technically much more difficult in small children and there is very limited published knowledge in this age group. We here present treatment and outcome of young children with renovascular hypertension at our institution. Children below 2 years of age, with renovascular hypertension between January 1998 and March 2020 were retrospectively reviewed. Demographics and treatment modalities were noted. Primary outcome was blood pressure within a week after the procedures and at last available visit. Sixty-six angiographies were performed in 34 patients. Median age at time of first angiography was 1.03 (interquartile range (IQR) 0.4–1.4) years and systolic blood pressure at presentation 130 (IQR 130–150) mm Hg. Thirty-eight percent (13/34) of children were incidentally diagnosed and 18% (6/34) presented with heart failure. Twenty-six (76%) children had main renal artery stenosis and 17 (50%) mid-aortic syndrome. Seventeen (50%) children showed intrarenal, six (18%) mesenteric, and three (9%) cerebrovascular involvement. Twenty patients underwent 45 percutaneous transluminal angioplasty procedures and seven children surgeries. In 44% of the 16 patients who underwent only percutaneous transluminal angioplasty blood pressure was normalized, 38% had improvement on same or decreased treatment and 19% showed no improvement. Complications were seen in 7.5% (5/66) of angiographies. In four of the seven (57%) children who underwent surgery blood pressure was normalized, two had improved (29%) and one unchanged (14%) blood pressure.Conclusion: In small children with renovascular hypertension below the age of 2 years, percutaneous transluminal angioplasty caused significant improvement in blood pressure with low complication profile. Surgery can be recommended where percutaneous transluminal angioplasty and medical treatments failed. Children with secondary hypertension have in 5–10% been found to have a renovascular disease –5.Interventional treatment with percutaneous transluminal angioplasty has over the last decades become commonly used in children with renovascular hypertension while surgery previously was the treatment of choice –8. Both In the literature, there are very few patients under the age of 2 years , 9, 10 aChildren with hypertension and a suspicion of a renovascular cause aged 2 years and younger at the time of intervention, who underwent digital substraction angiography between January 1998 and March 2020, were included in the study. The criteria used to perform the angiography were very high blood pressure, secondary symptoms of blood pressure like cardiac or neurological symptoms, uncontrolled hypertension with two or more antihypertensive drugs, diagnosis of a syndrome with a high risk of vascular disease, signs of vasculitis, previous vascular insult, bruit heard over renal arteries, raised plasma renin, or moderate hypokalemia [For patients older than 1 year of age, hypertension was defined when blood pressure was measured above the 95th percentile for individualized age-sex-height provided by Lurbe et al. . In chilAll children underwent diagnostic angiography before any interventional procedures. In some patients, magnetic resonance (MR) or computerized tomography (CT) angiography were used for further anatomic evaluation of the abdominal vasculature. When clinically indicated cerebral MR angiography (MRA) or CT angiography (CTA) was performed.Angioplasties were performed by a pediatric interventional radiologist under general anesthesia. Arterial access  was obtained by ultrasound guided insertion of a valved sheath. For angioplasty, balloon size was selected according to the estimated normal renal artery size and to avoid thrombosis aspirin was used.Clinical outcome was graded according to suggestions of Ellis et al.: (1) normalized blood pressure , no antihypertensive treatment; (2) improved blood pressure with same or reduced treatment; (3) unchanged blood pressure or increased antihypertensive treatment; (4) technical failure (unable to pass the catheter or dilate the vessel) .Short-term outcome was defined as blood pressure within a week after the procedures and long-term at last available visit. The Schwartz formula was used to calculate estimated glomerular filtration rate (eGFR) .U test and categorical variables by Chi-square or Fisher’s exact test as appropriate. A p value of < 0.05 was considered statistically significant.Data analyses were performed by using SPSS Version 21.0 . Samples were tested with Shapiro–Wilk test to determine normality of distributions. According to the results, nonparametric tests were preferred. Continuous variables were compared by Mann–Whitney Thirty-seven children below the age of 2 years who underwent diagnostic angiography with suspected renovascular hypertension were assessed for eligibility. Among them three patients with normal angiography findings were excluded and a total of 34 patients were included in the final analysis. Male/female ratio was 15:19.At the time of the first angiography at the authors’ institution four had had previous angioplasties. Seven children had a history of previous procedure or surgery. Nine children had an underlying syndrome; there were two cases of neurofibromatosis type 1 (NF-1), one Hurler’s syndrome, one Treacher-Collins syndrome, one Williams-Beuren syndrome, two other patients with phacomatoses and two patients with undefined syndromes.At presentation, eight patients had elevated serum creatinine and two of them had known underlying renal parenchymal conditions. Two children had single kidneys, one unilateral hypoplasia and the other unilateral nephrectomy. Demographic, clinical, and laboratory characteristics of patients are given in Table The clinical presentations of the children at the time of first angiography at the authors’ institution are shown in Table Results of echocardiography were available in 29 patients, 18 had mild left ventricular hypertrophy, six had moderate-severe cardiac involvement while five were normal.Renal ultrasonography was performed in all children and was found to be normal on both sides in 16 patients and in both children with solitary kidneys. Pathological ultrasound findings with decreased renal size and/or increased echogenicity were seen in the remaining children. Ultrasound sensitivity was calculated as 44%. Renal Doppler ultrasound was performed in 30 patients and was normal in eight patients and in the two patients with solitary kidneys. Doppler ultrasound sensitivity was 63%. Dimercaptosuccinic acid (DMSA) scintigraphy was performed in 27 patients, was bilaterally normal in eight patients and normal in one of the patients with solitary kidney. Computerized tomography angiography was performed in four patients and missed intrarenal involvement in one patient. Magnetic resonance angiography was performed in two patients, diagnosed mid-aortic syndrome but missed renal artery stenosis in both.In total, 34 patients underwent 66 angiographies Table . Nine paTwenty patients underwent 45 percutaneous transluminal angioplasties Fig. . Eight pA cutting balloon was used three times. All three cutting balloon angioplasties were performed in patients diagnosed with phacomatoses (two with NF-1). Interventions on a previous vascular graft were performed in two angioplasty procedures. One child had one renal artery stented twice; the second time due to in-stent stenosis in the previously placed stent.The median time interval to second angioplasty after the first procedure was 5.5 IQR 4–10) months. The indication for the second angioplasty was clinically resistant hypertension in all cases. An anatomical restenosis was found in three children and a significant residual stenosis in nine (Table –10 monthEmbolization (ethanol ablation) was used succesfully for three patients. In two patients with unilateral polar renal artery stenosis only embolization was performed. In the third patient, ethanol ablation was used after two angioplasties  since the lesions were not amenable to angioplasty Fig. .Among 66 angiographies (45 angioplasties), complications were seen in five procedures; arterial dissections treated with balloon angioplasty in three patients and thrombosis successfully treated with anticoagulation in two. No complications were observed beyond the 2nd angioplasty.Seven children required surgical intervention. Three patients underwent unilateral nephrectomies. Four children had vascular surgery with one having surgical revascularization and unilateral nephrectomy (2.4 years old); one child underwent autotransplantation (6.5 years old); one patient had unilateral nephrectomy and an aortic graft (1.2 years old); and one had open thrombectomy (1 month old).Among the 20 patients who underwent angioplasty, after the first procedure, 15% (3/20) had normalized blood pressure, 45% (9/20) had blood pressure improvement on same or decreased treatment, 30% (6/20) showed no change in blood pressure or had increased treatment, and in 10% (2/20) technical failure was observed.p < 0.001).The median time to last follow-up from the first procedure was 13 months (IQR 2.8–86) and from the last procedure 2.5 months (IQR 0.3–49). The median number of antihypertensive medications at last visit had decreased to 0.5 (IQR 0–3) from 3 (IQR 2–4)  had normalized blood pressure, 37.5% (6/16) had blood pressure improvement on same or decreased treatment, and 18.5% (3/16) showed no change in blood pressure or had increased treatment. Of seven patients who underwent surgery, at last follow-up, four had normalized blood pressure, two had improved, and one had unchanged blood pressure values. All patients who underwent embolization normalized their blood pressure at last follow-up. Figure The nine patients diagnosed with a syndrome showed a similar pattern of improvement in the blood pressure.p = 0.172 for age, p = 0.273 for diagnosis).Table At last follow-up of the 25 patients who underwent any kind of intervention , 52% had normalized blood pressure and 32% had blood pressure improvement on same or decreased treatment. Four patients had at final follow-up a blood pressure that was unchanged.2, and median eGFR was 128 (IQR 91–146.5) mL/min/1.73 m2.At last visit, median serum creatinine was 32 (IQR 26.5–53) µmol/L. There were three children (8%) with an eGFR of < 90 mL/min/1.73 mDeath occured in four patients, none of which were procedure or hypertension related. One patient had neuroblastoma and died due to related complications. Another patient with Treacher-Collins syndrome died due to intracranial bleeding after an epileptic seizure. One patient died of multiorgan failure due to traumatic injury, and one patient with generalized arteriopathy and pulmonary hypertension died from heart failure.In this study, we describe successful outcome of angioplasty and/or surgery or embolization in children with renovascular hypertension below the age of 2 years. Clinical success at last follow-up  was achieved in 84% (21/25) of the patients who underwent angioplasties and/or surgeries with an acceptable complication profile (5/66 angiographic interventions). There was no kidney loss or mortality related to the angiographic procedures.An important number of the small children in our study presented with severe end-organ damage mainly in the heart with several having significant heart failure 18% and left ventricular hypertrophy in 83%. The indication for treatment was therefore strong. The literature on percutaneous transluminal angioplasty in small children is limited, with only some case reports and very few patients in some retrospective series , 15–17.The success rate of percutaneous transluminal angioplasty in older children varies between 50 and 100% –20. In oAs seen also in older children, it is not uncommon that the percutaneous transluminal angioplasty needs to be repeated either due to restenosis or significant remaining stenosis after the preceding procedure , 5. In tThere is no consensus regarding which diagnostic modalities to use in children with suspected renovascular hypertension. In our present study, ultrasound with Doppler had a low sensitivity of only 63%, which is similar to a previous study in children of all ages . CTA andEnd-organ damage is an important effect of systemic hypertension. In previous studies among older children, left ventricular hypertrophy was found in approximately 66% of patients , 5. In tThe clinical success rate was also very good in our patients with a phacomatosis. This is a group who has been regarded as more difficult to treat than other children. We therefore suggest that also in young NF-1 patients percutaneous transluminal angioplasty can be a good option.Complication rates of percutaneous transluminal angioplasty in children range between 0 and 43% . We founLimitations to our study are its retrospective design and relatively short follow-up period, and also the long time period of the study. Prospective studies with longer follow-ups preferrably into adulthood are required to be able to define the genuine rates of normalized blood pressure in pediatric patients.In conclusion, angioplasty in infants below 2 years of age with renovascular hypertension, can be a safe and reliable treatment in experienced hands. However, its success rates decrease with multi-vessel and/or intrarenal involvement. Surgery can be recommended where percutaneous transluminal angioplasty and medical treatment are not effective to control blood pressure and preserve renal function.


To explore the predictors of death in acute ischemic stroke (AIS) patients within 1 year based on machine learning (ML) algorithms.This study retrospectively analyzed the clinical data of patients hospitalized and diagnosed with AIS in the Second Affiliated Hospital of Xuzhou Medical University between August 2017 and July 2019. The patients were randomly divided into training and validation sets at a ratio of 7:3, and the clinical characteristic variables of the patients were screened using univariate and multivariate logistics regression. Six ML algorithms, including logistic regression (LR), gradient boosting machine (GBM), extreme gradient boosting (XGB), random forest (RF), decision tree (DT), and naive Bayes classifier (NBC), were applied to develop models to predict death in AIS patients within 1 year. During training, a 10-fold cross-validation approach was used to validate the training set internally, and the models were interpreted using important ranking and the SHapley Additive exPlanations (SHAP) principle. The validation set was used to externally validate the models. Ultimately, the highest-performing model was selected to build a web-based calculator.https://mlmedicine-de-stroke-de-stroke-m5pijk.streamlitapp.com/) based on XGB to predict death in AIS patients within 1 year.Multivariate logistic regression analysis revealed that C-reactive protein (CRP), homocysteine (HCY) levels, stroke severity (SS), and the number of stroke lesions (NOS) were independent risk factors for death within 1 year in patients with AIS. The area under the curve value of the XGB model was 0.846, which was the highest among the six ML algorithms. Therefore, we built an ML network calculator (The network calculator based on the XGB model developed in this study can help clinicians make more personalized and rational clinical decisions. Acute ischemic stroke (AIS) is a disease caused by the occlusion of cerebral arteries, accompanied by brain tissue infarction and neuronal cell damage, causing severe trauma to the body. AIS is the leading cause of disability in adults and the primary cause of human death worldwide , 2. In 2ML-assisted clinical decision-making and analysis have been widely used in clinical settings –11, espeTherefore, this study aimed to develop and validate an interpretable ML model that used clinically relevant variables to predict death within 1 year in AIS patients and construct an easy-to-use web calculator as a convenient and practical protective tool for clinical practitioners to provide valid information for AIS patients.Patients who were hospitalized in the Department of Neurology of the Second Affiliated Hospital of Xuzhou Medical University and diagnosed with AIS between August 2017 and July 2019 were retrospectively analyzed. A total of 677 patients with AIS were included in this study, 32 of whom died after admission and during follow-up. The study was approved by the Ethics Committee of the Second Affiliated Hospital of Xuzhou Medical University [ethics number: [2020] 081603], and all patients provided written informed consent.The inclusion criteria were a diagnosis of AIS in accordance with the World Health Organization criteria, and the time between onset and hospital admission did not exceed 24 h. The exclusion criteria were: (1) incomplete clinical data, (2) those with severely abnormal organ function, (3) inadequate ancillary investigations, (4) follow-up of <1 year, and (5) Patients who discontinued treatment for various reasons according to their relatives.In this study, clinical data were collected from the enrolled patients, including demographics (age and sex); vascular risk factors ; baseline blood pressure [systolic blood pressure (SBP) and diastolic blood pressure (DBP)]; Trial of Org 10 172 in Acute Stroke Treatment (TOAST) ; stroke severity (SS) ; magnetic resonance imaging (MRI) features ; laboratory tests , treatment regimen ; and stroke comorbidities [dysphagia and stroke-associated pneumonia (SAP)].t-tests and the categorical variables were compared using χ2-tests. Understanding the relationship between the independent and dependent variables was clinically meaningful and P-values of <0.05 were considered statistically significant (two-sided).This study used R version 4.0.5 software for data processing and statistical analyses. Continuous variables are expressed as the median or interquartile range (IQR) while categorical variables are presented as frequencies . The continuous variables were compared by independent samples P < 0.05 considered to indicate a statistically significant difference. Then, the factors that were significant in both univariate and multivariate logistic regression were included and subjected to stepwise regression analysis. The factors selected by stepwise regression were used as input variables to construct ML models.Univariate and multivariate logistic regression analyses were used to assess the risk factors of death within 1 year in the training group study population. The odds ratio (OR) and 95% confidence interval (CI) were calculated, with an OR of > 1 indicating that the variable was a risk factor, and The ML algorithm process was based on Python (V3.7) software and the scikit-learn (version 0.24) library. First, the original dataset was randomly divided into training and test sets at a ratio of 7:3. Then, six machine algorithms  were used to analyze the data and construct the model. To validate the predictive power of the model, the 10-fold cross-validation method was used for internal validation against the training group. The random search method was used to adjust the hyperparameters of the models.In the test group, the area under the receiver operating characteristic curve (ROC-AUC), classification accuracy, recall, specificity, and F1 score were used to evaluate the prediction models. We also plotted the prediction recall curve (PRC) as a complementary metric to evaluate the model performance.To illustrate the risk factors of death within 1 year in AIS patients, Shapley Additive explanation (SHAP) analysis was used to interpret the predictive models ranked in terms of feature importance. SHAP analysis is a tool proposed by Lloyd Shapley in game theory to explain the output of machine learning models. The core idea is to calculate the marginal contribution of a variable feature when it is added to the model, and then to interpret the global and local levels of the “black box model” in an additive explanatory model , 15. ThaIn this study, clinical information was collected on 677 AIS patients, of whom 645 survived and 32 died of AIS . In the The median systolic and diastolic blood pressure was 143 mmHg  and 87 mmHg , respectively. Total cholesterol, triglycerides, HDL, blood HCY, blood UA, and median FIB, MB, ultrasensitive CRP, D-dimer BNP, atrial natriuretic peptide, NSE, and S-100β were 5.3 mmol/L , 2.2 mmol/L , 4.8 mmol/L , 15.7 μmol/L , 349.8 μmol/L , 4. 3 g/L , 97. 7 ng/mL , 12. 2 mg/L , 174.0 ng/mL , 93.0 ng/mL , 16.2 ng/mL , and 275.0 ng/mL , respectively.P < 0.05) in the overall population for death within 1 year according to NOS, FBG, HBALC, MB, and CRP levels, as well as anticoagulation therapy, PPI treatment, and SS.In the univariate regression analysis of death within 1 year in AIS patients , there wP = 0.007), HCY , CRP , and SS  were independent predictors of death within 1 year in AIS patients.All parameters that were statistically different in the univariate analysis above were included in the multivariate logistic regression analysis. The results suggested that NOS -kB, which is a transcription factor common to inflammation and the immune response. Elevated levels of HCY are associated with a variety of diseases, which may lead to endothelial dysfunction, neurotoxicity, and the upregulation of thrombogenic factors. At the same time, monitoring HCY levels may provide a good indication of the development of related diseases , SS, and NOS are independent risk factors of death within 1 year in AIS patients. The XGB algorithm showed good performance as a tool to predict death within 1 year in AIS patients. Using this web-based calculator can effectively prevent death, reduce mortality, and assist physicians in making treatment decisions.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The study was written approved by the Ethics Committee of the Second Affiliated Hospital of Xuzhou Medical University [ethics number: [2020] 081603]. The patients/participants provided their written informed consent to participate in this study.WLi, LR, and XW completed the study design. KW, WLiu, and WLi performed the study and collected and analyzed the data. LG and WLi drafted the manuscript. LR, XW, KW, and HL provided the expert consultations and suggestions. CX and CY conceived of the study, participated in its design and coordination, and helped to embellish language. All authors reviewed the final version of the manuscript.


Pulse wave velocity (PWV) is a measure of arterial stiffness. We investigated PWV and blood pressure (BP) to determine to what extent BP changes contribute to arterial stiffness, and secondly, to identify influencing factors on BP in children after kidney transplantation.z-score (PWVz) adjusted either for Δ SBP or Δ DBP was performed. An extended dataset with monthly entries of BP, immunosuppression, and creatinine was obtained in 35 participants over a median of 74 months to perform linear mixed modeling for SBP and DBP.Seventy children ≥ 2.5 years post-transplantation with at least two PWV measurements were included. Changes of systolic (Δ SBP) and diastolic BP (Δ DBP) were classified into “stable/decreasing,” “1–10 mmHg increase,” and “ > 10 mmHg increase.” Linear mixed modeling for PWV CI 0.054 to 0.16). Compared to participants with stable BP, those with 1–10-mmHg SBP and DBP increase showed a higher PWVz of 0.59 (95% CI 0.046 to 1.13) and 0.86 (95% CI 0.43 to 1.30), respectively. A > 10-mmHg BP increase was associated with an even higher PWVz . Female sex and participants with lower eGFR showed higher PWVz.PWVz increased with a rate of 0.11/year (95% In the extended analysis, DBP was positively associated with cyclosporin A and everolimus trough levels.A higher increase of PWV is seen in patients with greater BP increase, with higher cyclosporin A and everolimus trough levels associated with higher BP. This emphasizes the role of BP as a modifiable risk factor for the improvement of cardiovascular outcome after transplantation.The online version contains supplementary material available at 10.1007/s00467-022-05611-4. Cardiovascular mortality in children with kidney failure is very high. About 30% of deaths in children on dialysis and 25% in children undergoing kidney transplantation (KTx) are due to cardiovascular events . Data frThe scarcity of cardiovascular mortality as well as major cardiovascular events in pediatric patients with chronic kidney disease (CKD) makes these endpoints unsuitable for studies in children. Arteriosclerosis, a marker for subclinical cardiovascular damage, is the process where elastic fibers are replaced by stiffer collagenous fibers after they break down due to daily wear and tear, which is eventually followed by the calcification of the media layer. This process is a major element in the stiffening of large arteries, which can be assessed by pulse wave velocity (PWV). PWV is highly predictive of major cardiovascular events and cardiovascular mortality in adults . AlthougA strong dependency between arterial stiffness and blood pressure (BP) is established for healthy children , 14 and We aimed to decipher the association between BP changes and progression of arterial stiffness. Our specific goal was to determine a clinically applicable BP range that may aggravate arterial stiffness in pediatric KTx recipients late after transplantation. By using an extended dataset with monthly entries over a period of up to 9 years, we aimed to further explore which factors are potentially associated with higher BP in a sub-cohort of our patients.n = 41, University Medical Center Hamburg-Eppendorf n = 22, and Hannover Medical School n = 61) were enrolled in this prospective multicenter cohort study [From January 2011 to August 2019, 124 pediatric KTx recipients from three German pediatric nephrology units  adjusted for sex and height [As our primary endpoint, PWV measurements were transformed to standardized score (d height . Furtherz-score for BP [z-score for BMI. The estimated glomerular filtration rate (eGFR) was calculated using the Schwartz formula [We calculated age-, height-, and sex-standardized e for BP , 28, as  formula . Immunosz-score ≥ 1.645) for patients with age < 16 years, or as a systolic/diastolic BP ≥ 140/90 mmHg for those ≥ 16 years old, or if the patient was on antihypertensive medication [The change of BP was calculated as the difference between the BP at each given visit and the BP at the first visit at ≥ 2.5 years after transplantation (baseline visit). We classified the change of BP into three categories: “stable/decrease,” “1–10 mmHg increase,” and “ > 10 mmHg increase.” Hypertensive BP was defined as systolic and/or diastolic BP ≥ 95th percentile  for PWV z-score (PWVz) at follow-up visits (after baseline visits), adjusted for sex [p-value of < 0.05 was considered statistically significant. Statistical analysis was performed using SAS 9.4 .Continuous variables are summarized by means  and categorical variables by frequencies and percentages. Differences between two or more independent groups were assessed using ANOVA or χ for sex , 12, 30, for sex , BMI [31 for sex  at the r for sex , and und for sex , and eGFn = 43 males) with at least two visits were included, resulting in 211 observations. At baseline, the age was 12.6 ± 3.2 years and elapsed time since transplantation was 6.1 ± 3.1 years. Participants were followed up for 4.0 ± 2.0 years with a maximum follow-up of 8 years. Fifty-one participants were transplanted after prior dialysis. The mean eGFR at the baseline visit was 56.6 ± 26.5 mL/min/1.73 m2. Detailed participant characteristics are given in Table Of 124 pediatric KTx recipients, 70 . The proportion of hypertension remained high over time, and the proportion of uncontrolled hypertension increased to 28% at the first follow-up visit  or three (21%) immunosuppressive agents. The majority received a CNI-based regimen (97%), with CNI-mTOR, CNI-MMF, and CNI-steroids as the most commonly used combinations  . A systolic BP increase of > 10 mmHg was associated with an even higher PWVz increase of 0.78 (95% CI 0.22 to 1.34). Significant associations between female sex, non-CAKUT underlying disease, and a lower eGFR with a higher PWVz were shown . An increase in diastolic BP of > 10 mmHg was associated with a higher PWVz of 1.37 (95% CI 0.80 to 1.94). A higher PWVz was also associated with a higher baseline diastolic BP and female sex.The model for PWVz and changes in diastolic BP Table  showed aIn both models adjusted for changes in systolic and diastolic BP, age and BMI did not reveal a significant association with PWVz Tables  and 3. Wn = 20 males) comprising 2137 observations. The participants’ characteristics of the extended dataset are given in Supplemental Table We used an extended dataset to evaluate the importance of immunosuppression on BP. We retrieved data on systolic and diastolic BP, eGFR, and immunosuppressive trough levels from 35 participants  and everolimus . Diastolic BP increased with age (DOCX 32.7 KB)Below is the link to the electronic supplementary material.


In the training cohort, univariate and multivariate logistic regression analyses were performed, and a simple nomogram was built using the stepwise method. The receiver operating characteristic (ROC), calibration curve, and decision curve analysis were computed in order to validate the discrimination and clinical value of the nomogram model. Results: About 65.7% and 72.2% of patients were diagnosed with DPN in the training and validation cohorts. We developed a novel nomogram to predict the probability of DPN based on the parameters of age, gender, duration of diabetes, body mass index, uric acid, hemoglobin A1c, and free triiodothyronine. The areas under the curves (AUCs) of the nomogram model were 0.763 in the training cohort and 0.755 in the validation cohort. The calibration plots revealed well-fitted accuracy between the predicted and actual probability in the training and validation cohorts. Decision curve analysis confirmed the clinical value of the nomogram. In subgroup analysis, the predictive ability of the nomogram model was strong. Conclusions: The nomogram of age, gender, duration of diabetes, body mass index, uric acid, hemoglobin A1c, and free triiodothyronine may assist clinicians with the early identification of DPN in patients with type 2 diabetes mellitus.Background and Purpose: Diabetic peripheral neuropathy (DPN) leads to ulceration, noninvasive amputation, and long-term disability. This study aimed to develop and validate a nomogram for forecasting the probability of DPN in type 2 diabetes mellitus patients. Methods: From February 2017 to May 2021, 778 patients with type 2 diabetes mellitus were included in this study. We confirmed the diagnosis of DPN according to the Toronto Expert Consensus. Patients were randomly divided into a training cohort ( Diabetic peripheral neuropathy (DPN), a common microvascular complication of type 2 diabetes ,2, increAn effective diabetic retinopathy prediction model can provide cost-effective and readily accessible risk predictions for patients with type 2 diabetes mellitus . A recenThis cross-sectional study was conducted in the inpatient department of the First Affiliated Hospital of Wenzhou Medical University from February 2017 to May 2021. Participants diagnosed with type 2 diabetes mellitus were continuously enrolled in the study. The diagnosis of type 2 diabetes mellitus was based on the 2017 criteria of the American Diabetes Association (ADA) . All patAll subjects accepted neurological assessment using the neuropathy symptom score (NSS) and neuropathy disability score (NDS) ,14,15. TElectrophysiological examinations were carried out by experienced technicians with the electromyography instrument . Patients kept limb skin temperature between 32 to 35 ℃ during testing. The compound muscle action potential (CMAP) amplitude, distal latency, and conduction velocity (CV) of bilateral ulnar, median, tibial, and common peroneal nerves were measured for motor nerves. The sensory nerve action potential (SNAP) amplitude and CV of bilateral ulnar, median and superficial peroneal nerves were measured for the sensory nerve. Bilateral measurements of the F-wave latency of the tibial nerve were also calculated. The data of healthy individuals in the neurophysiology laboratory of Peking Union Medical College Hospital were used as reference values. Electrophysiological experts judged abnormal NCSs based on the abnormality of one or more attributes in two or more nerves . In addiInformation about medical history, physical examination, and clinical data, including age, gender, duration of diabetes (duration), body mass index (BMI), history of smoking, hypertension, and dyslipidemia, were collected from electronic medical records. After 8–10 hours of overnight fasting, blood samples were obtained in the morning. Routine blood tests, including neutrophils, lymphocytes, and platelet (PLT), were determined by an autoanalyzer . NLR was defined as the ratio of neutrophil count to lymphocyte count. Hemoglobin A1c (HbA1c) was measured by high-performance liquid chromatography. Uric acid (UA), fasting plasma glucose (FPG), total cholesterol (TC), triglyceride, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were determined by an automated chemistry analyzer . Free triiodothyronine (FT3), free thyronine (FT4), and thyroid stimulating hormone (TSH) were measured by an automatic chemiluminescence analyzer . Fibrinogen (FIB) was determined by an automated coagulation analyzer .Finally, 778 patients with type 2 diabetes were included in this study. The patients were randomly divided into two groups .t-tests or the Kruskal–Wallis test were used to compare the difference between two groups in continuous variables. Categorical variables were represented as frequencies (percentages) and compared using Chi-square tests between the two groups. We performed the Shapiro–Wilk test to determine whether the variable conformed to the normal distribution. Continuous variables with normal distributions were represented as mean ± standard deviation (SD), and continuous variables with skewed distribution were described as median ± interquartile ranges. Student’s p < 0.05 variables from the univariate logistic regression. According to previous studies, the clinical variables recognized as critical factors were also entered into the multivariate logistic regression analyses. Variables with p < 0.05 in the multivariable analysis were retained to establish a nomogram in the training group. The score for each variable was calculated based on the regression coefficient values.The comparison of baseline characteristics of the training cohort stratified by the presence of DPN were presented. First, all variables were assessed using univariate analysis between the DPN group and the non-DPN group, and univariate logistic regression was used to identify the risk factors of DPN in the training cohort. Secondly, the stepwise multivariate logistic regression analyses were performed with p < 0.05 was considered statistically significant. All of the statistical analyses were performed with statistical packages R version 3.5.1 and SPSS Version 24.0 .The validation of the nomogram model consisted of two parts. Initially, the areas under the curve (AUC) of the receiver operating characteristic (ROC) were used to evaluate the nomogram's discrimination capacity in the training cohort. We also conducted the AUC with a 95% CI using 500 bootstrap resamplings for internal validation. The calibration curve was assessed graphically by smoothing a scatter plot of the predicted and actual probabilities. Decision curve analysis (DCA) was performed in order to determine the clinical net benefit of the model. Second, the ROC, calibration curve, and DCA were also performed in the validation cohort. Correlations between variables in the nomogram and NCSs parameters were assessed using Pearson's or Spearman's test in all of the patients. Then, multiple linear regression analysis was executed in order to identify the relationship between variables in the nomogram and NCS parameters. Two-sided n = 519) and a validation cohort (n = 259). About 65.7% and 72.2% of patients were diagnosed with DPN in the training and validation cohorts. The differences in baseline characteristics between these two were insignificant , 500 umol/L of UA (30 points), 7 of HbA1c (10 points), and 8 pmol/L of FT3 (50 points). He receives a total score of 190 points by adding all the points. The estimated probability of DPN for this patient is less than 50%.Based on the multivariable logistic regression analysis, the nomogram was developed for predicting DPN risk based on gender, age, duration, BMI, UA, HbA1c, and FT3 in the training cohort . Data weThe AUC of the nomogram was 0.763 for the training cohort , and theIn In the present study, we established a practical and simple nomogram to predict the probability of DPN tailored to individual patients. The predictive nomogram showed good discriminatory strength and moderate clinical value in training and validation cohorts. Our nomogram is based on gender, age, duration, BMI, UA, HbA1c, and FT3 to provide a user-friendly and convenient tool for clinical practice. In addition, the performance of the nomogram was beneficial and stable in various subgroups. Furthermore, the independent factors in the nomogram were also independently associated with NCS parameters.The diagnostic criteria of DPN varied in different studies ,19,20,21The risk factors included in this nomogram are similar to the results of other prediction models. Advancing age is a nonmodifiable independent predictor for DPN . Many stThe present study also investigated the associations between DPN and other important risk factors. The relationship between BMI and DPN is still controversial. Previous studies have suggested that BMI was positively linked to DPN ,25. NevePoor glycemic control, such as increased HbA1c, was related to a higher DPN risk in the TODAY cohort . We obseThe present study has some remarkable strengths. Our study demonstrated good discrimination and predictability of the nomogram for DPN with factors that can be readily obtained in general healthcare settings. The predictive power of the nomogram model was suitable and stable in various clinical subgroups, suggesting that it could be widely used in clinical practice. NCSs were considered a gold standard for the diagnosis of DPN. Moreover, the risk factors of the nomogram were independently associated with NCS parameters, indicating a close connection between the nomogram model and nerve conduction function.First, this was a single-center study that was only applicable to patients with type 2 diabetes and could not be applied to communities of type 1 diabetes patients. Second, we did not collect information on other complications of T2DM and genetic markers. These tests may, however, increase the cost of DPN screening and other clinical indicators. In conclusion, the nomogram model is composed of age, gender, duration of diabetes, BMI, UA, HbA1c, and FT3, has a good predictive ability of DPN in patients with type 2 diabetes mellitus. Since NCSs are uncomfortable and expensive, developing a tool for limited healthcare resource providers in rural areas is beneficial. Due to its simplicity and applicability, this nomogram might be generalized for clinical practice and identifies patients with high DPN risk at the early stage.


Chronic Kidney Disease (CKD) is defined as “abnormalities of kidney structure or function, present for more than 3 months, with health implications” and is classified according to the cause, the glomerular filtration rate (GFR) category, and the magnitude of albuminuria  is central for the practice of nephrology in particular and medicine in general. Taking into account its limitations, at present, eGFR is not only a powerful tool for identifying CKD, but it has become fundamental for physicians for early detection, clinical diagnosis, monitoring of progression, indication for admission to replacement therapy, calculation of the dose of drugs excreted by the kidney, and in preparation for invasive diagnostic or therapeutic procedures. As an epidemiological tool, eGFR is not only a simple method to estimate the global burden of CKD, but an instrument for identifying risk factors for progression, understanding the epidemiology of kidney disease concerning different social groups (particularly vulnerable ones), and establishing public policies that intend to reduce CKD at the population level. In kidney disease investigation, it is necessary to determine the risks and benefits of new drugs over CKD progression.This volume includes several updates on different aspects of GFR in CKD. The evolution from the physiologic concept of glomerular filtration until its measurement through GFR and its present use as a clinical and epidemiological health tool; to estimate GFR in different populations and clinical situations, such as in pediatrics, older adults, and kidney donors and in obese patients and individuals born with low birth weight, all are detailed in several manuscripts. There is also a good update on different equations for eGFR at different pediatric and adult ages.It is known, at least since the beginning of the century, that CKD increases the risk of cardiovascular disease and vice versa, as both diseases not only share some cardiovascular risk factors  but becaThe volume also includes several research articles.Once again, it was confirmed that metabolic acidosis, defined as a serum bicarbonate level < 22 mmol/l is an independent risk factor for kidney progression.< Low sUmod-High eGFR < High sUmod-low GFR < low sUmod-low eGFR was found. The conclusion was that sUmod additionally to creatinine or cystatin C enables a more precise risk modeling for all-cause and CV mortality.Serum uromodulin (sUmod), a biomarker of tubular mass and kidney function, in patients referred for coronary angiography showed a linear increase in all-cause and CV mortality, from the group with high sUmod-high eGFR Using data from the NANES 2017-2018, the interactive impacts of smoking (a modifiable risk factor) and sleep on kidney function were studied in a cross-sectional study; the results showed that normal sleep duration was a protective and more crucial factor for non-smokers than for smokers.>7.5 mg/dl is a probable optimal cutoff value for predicting kidney function deterioration.The study about uric acid and impairment of renal function in non-diabetic hypertensive patients concluded a uric acid level In older adults with CKD followed longitudinally, the patent of deterioration of GFR and malnourishment predicted mortality and kidney failure.A1c. The simultaneous increase in sodium excretion reverses the tubule-glomerular feedback, reducing the mechanism of damage of glomerular hyperfiltration and slowing the progression of CKD. Calorie loss from glycosuria results in weight loss, increased insulin sensitivity, enhanced lipid metabolism, and probably lessened lipotoxicity. Metabolism moves toward gluconeogenesis and ketogenesis, two probably protective effects for the heart and the kidneys.Finally, two manuscripts focused on the novel effects of two drugs in CKD: Sodium-Glucose Cotransporter 2 inhibitors (SGLT2i) or gliflozins, and vitamin D. About the SGLT2i, the different proposed mechanisms of action which would result in improving cardiac and renal outcomes are described. Briefly: SGLT2i inhibits renal glucose reabsorption at the proximal tubules by blocking the SGLT2 cotransporters; the resulting glycosuria reduces hyperglycemia and improves HbThe manuscript Non-classical Vitamin D Actions for Renal Protection aimed to update on CKD-induced alterations in both systemic and local bioactivation of vitamin D and calcitriol actions, and to develop strategies to effectively reduce the progression of CKD, without considering the extent of secondary hyperparathyroidism but attenuating its most potent inducers: systemic inflammation, arterial hypertension, and renal and CV damage. The pathophysiology that causes the reduction mediated by calcitriol/VDR (vitamin D receptor) in the proinflammatory and hypertensive signals not related to the decrease in klotho was analyzed.Some conclusions emerge from this volume:GFR continues to be a powerful tool for the diagnosis and follow-up of CKD patients and as an epidemiology tool.Physicians should be alert about clinical situations where persistent hyperfiltration is present as a mechanism of damage .Scopes and limitations of eGFR must be known, so as to identify when mGFR should be preferred.Kidney function deterioration increases the risk of CV-related death in CKD and other non-communicable chronic diseases.New drugs, like gliflozins, will contribute to reducing both the progression of CV disease and CKD, added to angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists.What can we expect about eGFR in the near future? Probably GFR estimation should advance to population-type specific equations, with the race component resolved. In obesity stages II and III, the research could conclude in original formulas for estimating GFR and resolve the doubt about standardizing or not to body surface area. Finally, the recent description of the shrunken pore syndrome, diagnosed by a ratio eGFRcystatin C/eGFRcreatinine < 0.60 , which cAll authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.


BackgroundRenal involvement in monoclonal gammopathies presents with different clinico-morphological patterns and can manifest at the onset or the late phase of hematological disease, or after chemotherapy. The spectrum is ever-expanding with advancements in diagnostic methods. Renal biopsy is needed for accurate diagnosis, as each of these patterns carries therapeutic and prognostic implications.MethodsA total of 41 cases of monoclonal gammopathies were included in the study. Clinical, biochemical, and hematological details were obtained, and pathological variables were observed. Patients were followed till the maximum possible period, and treatment history and follow-up creatinine details were collected.ResultsThe spectrum of renal biopsy lesions observed included light chain cast nephropathy (LCCN) n=19, amyloidosis n=11, monoclonal immunoglobulin deposition disease (MIDD) n=6, and proliferative glomerulonephritis with monoclonal immunoglobulin deposition (PGNMID) n=5; 10 of these cases can be categorized as monoclonal gammopathy of renal significance (MGRS). Acute kidney injury (AKI) (41%) is the predominant clinical presentation in general whereas the majority of amyloidosis cases presented with nephrotic and sub-nephrotic proteinuria. LCCN cases had high serum creatinine and calcium, positivity for M-spike, as well as a high FLC ratio, compared to the other types. Around 100% of LCCN and MIDD patients had myeloma and 100% of PGNMID cases had normal marrow.ConclusionMore than three-fourths of patients were diagnosed with monoclonal gammopathies with biochemical and hematological workups after an initial kidney biopsy. The clinicopathological profile of these patients had a broad spectrum but there were still some consistent findings within the different types. A subgroup of patients (MGRS) had undetectable serum paraproteins but had monoclonal immunoglobulin deposition in the kidney. According to Santostefano et al., “monoclonal gammopathies (MG) include various clinicopathological entities characterized by B-cells or lymphoplasmacytic cell synthesis with tissue deposition of whole monoclonal immunoglobulin (Ig) or Ig subunits, constituting light chains (LC) or heavy chains (HC) or both (HLC)” . These pMG can involve either glomerulus, tubules, interstitium, and blood vessels alone or in combination. A morphologic diagnosis is seldom possible on clinical grounds. A renal biopsy helps in the accurate diagnosis of the pattern of injury, clonality, and ultra-structural details. It also aids in differentiating renal lesions due to plasma cell dyscrasias from its mimickers early in the course, as the etiology carries therapeutic and prognostic implications if the plasma cell disorder is identified early even before the hematological manifestations .The typical renal lesions in MG include light chain cast nephropathy (LCCN), amyloidosis, and monoclonal immunoglobulin deposition disease (MIDD) . HoweverThis study was approved by the Institute Ethics Committee for Human Studies at Jawaharlal Nehru Institute of Post Graduate Medical Education and Research (JIPMER), Puducherry, India. All diagnosed cases of monoclonal gammopathy with renal involvement  guidelines) that were screened wherever the kidney biopsies were indicated from 2011 to 2018 were chosen for the study after including the cases where the study patient’s relevant clinical, hematological and biochemical parameters were obtained. Pathological parameters were examined for bone marrow aspirate as well as bone marrow and kidney biopsies, and patients were followed up for the maximum possible period.Kidney biopsy light microscopy sections were stained by H&E, periodic-acid Schiff (PAS), Masson’s trichrome (MT), and periodic silver methenamine (PASM) and congo-red wherever needed. Immunohistochemical markers κ, λ, AA, CD138, CD38, CD20, CD56, and for immunofluorescence (IF) studies 3 micron cryostat sections were stained with fluorescein isothiocyanate conjugated antibodies IgG, IgM, IgA, κ, λ, C3, C1q. Electron microscopic (EM) examination of the tissue was not done in any of the cases due to the non-availability of EM at our institution.Statistical analysis was done using Statistical Package for the Social Sciences (SPSS) software v.23 . The categorical distribution is presented as frequency and percentages, and continuous variables are shown as mean with standard deviation. One-way ANOVA is used for finding a difference in means for parametric continuous variables among the kidney disease types. The chi-square test was used for finding an association of categorical variables like morphological findings, marrow plasma cell distribution pattern, marrow diagnosis, and urinary sediments in relation to kidney disease types. Differences were considered significant at a p-value of < 0.05.The spectrum of paraprotein-associated kidney disease observed included LCCN in 19 patients (46%), amyloidosis (AA negative) in 11 patients (27%), MIDD in six patients (15%), and proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) in five patients (12%). Among the patients in the Bone marrow (BM) study, all the cases of LCCN and MIDD had myeloma, but only 5 (45%) patients of amyloidosis had myeloma and all cases of PGNMID had normal marrow findings. The overall mean age was 56 ± 9.6 years and 62% of these cases were in the age group of 41-60 , MIDD (50%) and PGNMID (40%), and nephrotic syndrome (46%) in amyloidosis Table . In addiAround 78% of the patients had an initial diagnosis suggesting monoclonal gammopathy on kidney biopsy Table . The morBone marrow biopsy was available in 37 cases, of which myeloma Figure  was concPatients were followed for the maximum possible period/ till the end of the study period and the data is tabulated in Table . These pMonoclonal gammopathy of renal significance (MGRS)Five patients each with amyloidosis and PGNMID were qualified for MGRS with no detectable plasma cell clone except for light chain restriction in kidney biopsy. These cases had mean plasma cells of 6% in the bone marrow, no significant plasma cell clones, or serum paraprotein Tables -5.In our study, we observed a spectrum of paraprotein-associated kidney disease including LCCN (46%), amyloidosis (27%), MIDD 15%), and PGNMID (12%). Our study had a relatively higher incidence of PGNMID (12%) when compared to a study by Nasr et al [%, and PGAround 78% of the patients had an initial diagnosis suggesting monoclonal gammopathy on kidney biopsy which had no clinical suspicion. This was 100% in the cases with amyloidosis which could be due to the fact that 90% of amyloidosis patients were having renal impairments at the time of diagnosis, necessitating a kidney biopsy initially; this also was observed in a study by Gerth et al. .An overall male-to-female ratio was 3.1:1 and this male predominance was seen among all the disease types. Even though male predominance was common among kidney diseases with plasma cell dyscrasias, a slight female predominance was observed among the patients with amyloidosis by Montseny et al . StudiesThe mean kidney sizes on ultrasonography among the different disease types were within normal limits in our cases. Kidney in the plasma cell dyscrasias can be either normal, increased, or decreased in size depending on pathology as well as the duration of the disease as per Jennette et al.  but, an Biochemical findingsSerum calcium levels were within the normal range in all types but it is relatively higher in LCCN with a mean of 9.2 mg/dl which was similarly observed by Montseny et al.  and GertIn amyloidosis six cases had shown monoclonal protein in immunofixation electrophoresis (IFE) among which only three cases had shown positive M-spike in serum protein electrophoresis (SPEP) which was due to the higher sensitivity of IFE in detecting monoclonal protein. However, only SPEP had shown a statistically significant difference for M-spike positivity among the various paraproteinemic disease types which was comparable to Gerth et al. .Hematological findingsThe predominant marrow diagnosis observed was myeloma constituting 76% overall; 100% of the LCCN and MIDD had myeloma; contrary to the observations of Lin et al . Around Pathological findingsA total of 19 cases of light chain cast nephropathy were observed in our study out of which 16 cases had pure LCCN but three cases had mixed lesions; two with MIDD and one with amyloidosis. These mixed renal lesions in plasma cell dyscrasias are known and similar findings were observed by Lin et al. . All thrMorphological findings of amyloidosisfigure  are simiWith regards to MIDD, the majority of the cases had shown GBM thickening and PAS-positive mesangial expansion Figure , and thrDiffuse endocapillary proliferative glomerulonephritis pattern was seen in all five cases with PGNMID Figure . Also, tMonoclonal gammopathy of renal significanceWe observed 10 patients satisfying the criteria for MGRS. These patients had mean plasma cells of 6% in the bone marrow and no significant serum paraprotein levels which is similar to other studies in MGRS -18. MorpKidney biopsy is essential to establish the specific diagnosis, therapeutic, and important prognostic information in suspected cases of monoclonal gammopathy. The majority of the paraprotein-associated kidney disease cases in this study were initially diagnosed by kidney biopsy which signifies its importance. Paraprotein-associated lesions mainly LCCN, amyloidosis, and MIDD were encountered in kidney biopsies in a majority of these patients. These lesions had consistent findings among clinical and hematological variables. Even though hematological and biochemical investigations had detected monoclonal paraproteins in circulation, a subset of cases with low plasma cell burden and undetectable paraprotein in the serum but with monoclonal immunoglobulin deposition in the kidney like MGRS cases showed a reduction in the serum creatinine post-therapy.


Conversely, large insufflations can induce thoracic distension and jeopardize circulation. The capnogram  reproducing the CO2 patterns in human cadavers, (ii) assessing the influence of tidal volume and respiratory mechanics on thoracic distension using a mechanical lung model and (iii) exploring the impact of thoracic distension patterns on different circulation parameters during CPR on a pig model.(1) In out-of-hospital cardiac arrest patients, we identified on capnograms three patterns: intrathoracic airway closure, thoracic distension or regular pattern. An algorithm was designed to identify them automatically. (2) To link CO2 patterns in 5 cadavers. (ii) In the mechanical lung model, thoracic distension patterns were associated with higher volumes and longer time constants. (iii) In six pigs during CPR with various tidal volumes, a CO2 pattern of thoracic distension, but not tidal volume per se, was associated with a significant decrease in blood pressure and cerebral perfusion.(1) Clinical data: 202 capnograms were collected. Intrathoracic airway closure was present in 35%, thoracic distension in 22% and regular pattern in 43%. (2) Experiments: (i) Higher insufflated volumes reproduced thoracic distension CODuring CPR, capnograms reflecting intrathoracic airway closure, thoracic distension or regular pattern can be identified. In the animal experiment, a thoracic distension pattern on the capnogram is associated with a negative impact of ventilation on blood pressure and cerebral perfusion during CPR, not predicted by tidal volume per se.The online version contains supplementary material available at 10.1186/s13054-022-04156-0. The optidelines , 3. Howeretation , 5. We pretation . During retation . We rece2 patterns observed during CPR in a series of out-of-hospital cardiac arrest patients; (ii) to reproduce the CO2 pattern associated with thoracic distension on different experimental models; and (iii) to evaluate the impact of a thoracic distension capnogram pattern on ventilation and circulation in pigs during CPR performed with continuous chest compressions.The objectives of this study were: (i) to design an algorithm permitting to classify and assess the occurrence of the different CO2 signal obtained with chest compressions during the expiratory phase of the ventilatory cycle was labeled into one of the three patterns defined as follows:(i)Intrathoracic airway closure: oscillations due to chest compressions and decompressions are small or absent. Lung volume reduction far below the FRC and complete or partial intrathoracic airway closure explain this capnogram.(ii)Thoracic distension: oscillations due to chest compressions and decompressions are limited or absent at the beginning of the expiration phase and resume after a few chest compressions. Increase in lung volume above FRC explains this capnogram.(iii)Regular pattern: oscillations due to chest compressions and decompressions are clearly visible during the entire duration of the expiration phase. This pattern corresponds to the situation when neither thoracic distension nor intrathoracic airway closure is identified.Capnograms were analyzed as illustrated in Fig. 2 curve . As a result, “thoracic distension” is visible on the capnogram since it prevents several chest compression-induced CO2 oscillations. We computed the distension ratio as the ratio between the initial area under the CO2 curve without oscillation (AUC1) and the area of the consecutive normal CO2 oscillation (AUC2) as illustrated in Fig. 1 is two times superior to AUC2) was arbitrarily defined as a cut-off value; considering that the loss of oscillations in case of thoracic distension includes at least two inefficient chest decompressions (distension ratio ≥ 2). Calculations details are available in the Additional file To quantify thoracic distension, a distension ratio was defined based on the analysis of the area under the COation AUC and the 2 peaks corresponding to chest compressions-induced oscillations during the expiratory phase were identified.Maximum and minimum values of CO2 oscillations. An AOI lower than 30% was considered as intrathoracic airway closure. The threshold of 30% was defined based on the results of the Grieco et al.’s study showing that below an AOI of 30%, the impact on ventilation and as result on CO2 washout was substantial.Airway opening index (AOI) was calculated as defined by Grieco et al.  to quant1/AUC2 was then calculated  (authorization number CNIL 046461). All patients who were receiving manual continuous chest compressions after intubation according to international recommendations [n = 202), capnograms of 89 patients were already reported in a previous study [2 pattern was determined based on the classification algorithm described above, using a single representative ventilatory cycle for each patient. Patients were ventilated with a transport ventilator  using a bilevel pressure mode called CPV, with standardized ventilator settings: respiratory rate (RR) 10 breaths/min; inspiratory time 1 s and expiratory time 5 s (I/E = 1/5); inspired oxygen fraction (FiO2) 100%; inspiratory pressure 20 cmH2O; and positive end-expiratory pressure (PEEP) 5 cmH2O. Soon after intubation, CO2 signal was recorded and printed at airway opening from LifePak monitor/defibrillator  with a sidestream sensor placed between the Y-piece and the endotracheal tube. Data were prospectively collected without any interference with care. The study complied with the Declaration of Helsinki and was approved by the ethics committee of the University Hospital of Clermont-Ferrand, France (IRB no. 5891), with waiver of consent.The main objective of the present clinical series was to confirm the existence of the three COus study . The CO22 production in the Anatomy Laboratory of the Université Québec à Trois Rivières (UQTR) in Canada with five bodies (authorization number CER-14-201-08-06-17). Those cadavers were validated as a robust model to study ventilation during CPR [2 production have already been described; airway pressure, flow and esophageal pressure were recorded [2O) to generate a high range of tidal volumes. Ventilation cycles were classified according to the same algorithm used for the clinical study as intrathoracic airway closure, thoracic distension or regular pattern based only on the CO2 signal.To validate observations obtained from clinical data, the different conditions  were reproduced with Thiel embalmed human cadavers with simulation of COrecorded   and resistances (R = 5–10 cmH2O/L/s); capnograms were recorded under a large range of Vt (0.3 to 1L). For each combination of R × C and tidal volume, capnogram was analyzed to detect thoracic distension as described for both the clinical study and cadaver study.The objective of the bench study was to address the influence of respiratory mechanics and volume on thoracic distension CO’s study ) permittwas used  . The procedure for the care and killing of study animals was in accordance with the European Community Standards on the Care and Use of Laboratory Animals. A reporting checklist regarding animal preparation and study design is provided in Additional file We tested 7 female pigs weighing 28 ± 1 kg. A first animal was tested over a large range of tidal volumes (from 6 to 20 ml/kg) to illustrate what can be expected in terms of circulation impact and capnogram patterns.E 1/5, tidal volume 6 ml/kg). The LUCAS 3™  chest compression device could exert a mild active decompression effect due to the suction cup. CPR was organized into three periods associated with a specific tidal volume (period T0 to T5 => 5 min at 6 ml/kg-period T5 to T10 => 5 min at 12 ml/kg-period T10 to T15 => 5 min at 6 ml/kg). Blood gases were measured at each tidal volume change. Animals were killed at the end of the protocol  with a lethal dose of pentobarbital (60 mg kg−1). Details of animal preparation are available in Additional file Six animals were enrolled in the main study. Ventricular fibrillation was induced by a pacing wire inserted in the right ventricular through the femoral vein catheter. Fibrillation was left untreated during 4 min (no-flow period). Then, continuous mechanical chest compression was started at a rate of 100 per minute and a depth of 5 cm with ventilation as recommended . Data are summarized as mean (± SD) for continuous variables and count (%) for categorical variables. In the cadaver experiment, comparisons of tidal volumes between COCapnography was available in 202 patients soon after intubation during chest compressions, and all were included in the study. Patients’ characteristics and outcomes are described in Table From the 202 capnograms included in the study, 35% showed airway closure, 22% thoracic distension pattern and 43% regular pattern see Fig. . The mea2 patterns obtained with the Thiel cadavers. Thoracic distension based on capnogram was associated with higher tidal volumes compared with intrathoracic airway closure (p = 0.008) or regular pattern (p = 0.005) (after ANOVA). Mean tidal volume was 130 ± 136 ml for intrathoracic airway closure, 453 ± 222 ml for thoracic distension and 141 ± 82 ml for regular pattern. The mean distention ratio was 2.85 ± 1.56 (median 2.65) for all cadavers, 3.72 ± 1.21 (median 3.50) for thoracic distension and 1.23 ± 0.42 (median 1.22) for regular pattern.The characteristics of the cadavers are given in Additional file R × C). The larger the insufflated volume or the longer the time constant, the more likely thoracic distension was present. Thoracic distension was identified on capnograms with a frequency of 0%, 0%, 33%, 33%, 66%, 83%, 83% and 100% for insufflated volumes of, respectively, 300 ml, 400 ml, 500 ml, 600 ml, 700 ml, 800 ml, 900 ml and 1000 ml. Thoracic distension was detected on capnograms with a frequency of 13%, 50%, 38%, 50%, 75% and 75% for RC values of, respectively, 0.10 s, 0.2 s, 0.25, 0.40 s, 0.5 and 0.80 s.Table Intrathoracic airway closure was not observed in the animals enrolled in the experiment. Pigs’ characteristics are given in Additional file Vt increased. The capnogram depicted a change of the CO2 pattern from regular pattern to thoracic distension as Vt increased.Figure p = 0.002), mean blood pressure (p = 0.006), systolic blood pressure (p = 0.007) and diastolic blood pressure (p = 0.009). There was no significant effect on coronary perfusion pressure and carotid blood flow.The “distension ratio,” expressing the level of thoracic distension based on the capnogram Fig. , was sigVt and any recorded circulation parameter: coronary (p = 0.283) and cerebral (p = 0.998) perfusion pressure, mean (p = 0.839), systolic (p = 0.962) and diastolic (p = 0.882) blood pressure as well as carotid blood flow (p = 0.713).The different hemodynamic parameters recorded were not significantly impacted by tidal volume per se. There was no significant correlation between A time effect was present on the different hemodynamic parameters recorded except for coronary perfusion pressure, cerebral perfusion pressure and diastolic blood pressure.In the present series of capnograms, intrathoracic airway closure, thoracic distension and regular pattern concerned, respectively, 35%, 22% and 43% of 202 OHCA patients after intubation.R × C).The capnogram indicating thoracic distension was associated with higher tidal volumes on Thiel cadavers. Capnogram indicating thoracic distension on a CPR bench model was also more likely to occur with higher insufflated volumes or longer time constants  by limiting negative intrathoracic pressure during decompression , 13. ExpVt from 6 to 20 ml/kg magnified coronary and cerebral circulation oscillations related to ventilation and modified capnogram from regular to thoracic distension in parallel , where we observed that the stepwise increase of lel Fig. .2 pattern was reproduced on cadaver, bench and porcine models. This phenomenon was associated on average with higher insufflated volumes compared to intrathoracic airway closure or regular patterns. We found in the pig model that thoracic distension assessed by distension ratio was significantly and negatively correlated with mean arterial blood pressure and cerebral perfusion pressure, suggesting its potential negative impact on circulation during resuscitation.Thoracic distension COVt absolute values were not significantly associated with a negative effect on blood pressure, coronary perfusion and cerebral perfusion. Those results may suggest that the capnogram may be more relevant than Vt per se to predict a circulatory impact induced by ventilation.Unlike the capnogram, Vt, as we observed in some animals.The bench study provides a possible explanation for the previous observed result. Indeed, prolonged time constant that characterizes the time required to return to FRC may favor thoracic distension even with low In our series of 202 OHCA patients, thoracic distension and intrathoracic airway closure concerned 22% and 35% of patients, respectively. Interestingly, very similar capnograms have been reported during CPR, without specifically identifying the phenomenon of thoracic distension , 5.Vt. One cannot exclude that thoracic distension may be much more frequently observed with manual bag ventilation during which Vt and respiratory rate are poorly controlled, thus favoring the risk of hyperventilation. In addition, a moderate level of PEEP was used in our series, which could have minimized the occurrence of intrathoracic airway closure, favored by low airway pressures. Although our brief periods of recordings with one to ten cycles displayed similar patterns for all breaths, it is likely that CO2 patterns evolve along the course of CPR, and that the classification could change depending on the time of intervention, thus precluding any interpretation of its significance in terms of outcome.An important methodological point is that capnograms from the present study were captured soon after intubation with a respiratory rate of 10/min and a protective pressure mode of ventilation limiting Of note, intrathoracic airway closure was not observed during the animal experiment. It is possible that the pig thorax anatomy may limit the reduction of lung volumes we observe in humans during resuscitation and thus occurrence of intrathoracic airway closure. Besides, pig bronchial tree presents lateral connections that may also limit occurrence of distal airway closure . In addiVt delivered during manual bag ventilation [Excessive ventilation during cardiac arrest has already been shown to be associated with poor outcomes , 16. Nevtilation .Vt reduction could be proposed in case of thoracic distension. Further evidence is needed before developing such ventilatory approach on a ventilator, but these findings may be of potential additional value for bag valve mask ventilation during which hyperventilation is likely to occur.Based on these observations, a capnogram-based ventilation strategy may permit to optimize ventilation during CPR, using real-time identification of capnograms . As previously shown, PEEP increase may be considered in case of intrathoracic airway closure to open the airways, while First, the capnogram analysis proposed in the present study is based on continuous chest compression, and whether it is generalizable to an interrupted chest compression strategy ideally needs further assessment. But thoracic distension may also be present during interrupted chest compressions.2 pattern distribution to different CPR strategies  and renders hazardous outcomes’ interpretation.Second, capnogram from one ventilatory cycle recorded soon after intubation  was analyzed for each patient. This relatively limits the possibility to generalize CO2 via a catheter placed in the endotracheal tube resulted in significant additional resistance that favored early occurrence of thoracic distension as suggested by the observations obtained on the bench.Third, the specific setup in cadavers experiment to administer COIn the animal study, since each animal was its own control,several time-related factors might have also impacted circulation. Further studies comparing animals with different ventilation strategies are needed to confirm our observations.2 pattern indicating relative thoracic distension, which may be associated with a negative impact on blood pressure and cerebral perfusion, irrespective of tidal volume per se. This original capnogram classification has the potential to help optimizing ventilation during CPR.During CPR, intrathoracic airway closure, thoracic distension or regular pattern can be reliably identified by the capnogram analysis. We describe a novel COAdditional file 1: Methods. Distension ratio: calculation details. Human cadavers with simulation of CO2 production. Mechanical bench with simulation of CO2 production. Pig study: animal preparation.Additional file 2: Results. Clinical study from Grieco et al. Illustration of thoracic distension mechanism based on airway pressure, flow and CO2 analysis. Table S1: Cadavers’ characteristics. Table S2: Baseline pigs’ characteristics. Compliance to the ARRIVE Guidelines of the pigs’ experiment.