Preoperative Predictors of Adverse Clinical Outcome in Emergent Repair of Acute Type A Aortic Dissection in 15 Year Follow Up

Background: Acute type A aortic dissection (AAAD) has high mortality. Improvements in surgical technique have lowered mortality but postoperative functional status and decreased quality of life due to debilitating deficits remain of concern. Our study aims to identify preoperative conditions predictive of undesirable outcome to help guide perioperative management. Methods: We performed retrospective analysis of 394 cases of AAAD who underwent repair in our institution between 2001 and 2018. A combined endpoint of parameters was defined as (1) 30-day versus hospital mortality, (2) new neurological deficit, (3) new acute renal insufficiency requiring postoperative renal replacement, and (4) prolonged mechanical ventilation with need for tracheostomy. Results: Total survival/ follow-up time averaged 3.2 years with follow-up completeness of 94%. Endpoint was reached by 52.8%. Those had higher EuroSCORE II (7.5 versus 5.5), higher incidence of coronary artery disease (CAD) (9.2% versus 3.2%), neurological deficit (ND) upon presentation (26.4% versus 11.8%), cardiopulmonary resuscitation (CPR) (14.4% versus 1.6%) and intubation (RF) before surgery (16.9% versus 4.8%). 7-day mortality was 21.6% versus 0%. Hospital mortality 30.8% versus 0%. Conclusions: This 15-year follow up shows, that unfavorable postoperative clinical outcome is related to ND, CAD, CPR and RF on arrival.

Pregnancy, systemic lupus erythematosus and a short communication on labor complications as new onset of the disease

Systemic lupus erythematosus (SLE) occur frequently in women of fertile age. In the pathogenesis of SLE, estrogen plays an important role, hormonal changes such as pregnancy and the postpartum increase the risk of disease flares. Also, pregnancy in SLE patients carries a higher fetal risk compared with healthy women. Pregnancy outcome may be optimized by careful planning of the pregnancy and close follow-up of the mother and of the fetus. SLE is associated with high maternal and fetal risk especially when non-diagnosed before planning a pregnancy. Herein we present two cases of SLE manifested by preeclampsia and acute renal insufficiency during labor and postpartum period, with a difficult diagnosis after a few months of a worsening clinical situation.

A FATAL OUTCOME OF A NEONATAL DILATED CARDIOMYOPATHY: EVOLUTIVE NEONATAL LUPUS OR EARLIER CHILDHOOD- ONSET SYSTEMIC LUPUS? A CASE REPORT

Neonatal lupus is a rare congenital syndrome resulting from placental passage of maternal antibodies against SSA/Ro and/or SSB/La to the fetus. It is a generally benign condition, the cardiac involvement determining the prognosis. NNL is rarely manifested by isolated cardiomyopathy. The subsequent evolution towards systemic lupus is rare and unpredictable. We report the case of a daughter from a non-consanguineous marriage with healthy parents who presented a dilated cardiomyopathy in the first months of her life complicated by several outbreaks of heart failure. The spontaneous evolution was marked by the occurrence of skin lesions of the face and arms at the age of 10 years, then by the installation of episodes of hydrous retention at the age of 12 years complicated by an acute renal insufficiency with a rapid fatal outcome at the age of 15 years. ANA antibodies rate was at the threshold of positivity, antiDNA and ANCA were not detectable.C3 rate was low. Although a genetic cause can never be ruled out, the diagnosis was a systemic erythematous lupus SLE (an evolution of an eventual NNL or a childhood-onset systemic lupus). We propose a decision tree for the management of neonatal cardiomyopathy NCMP as a synthesis of the literature.The search for anti SSA/SSB must be part of the check-up usually requested at the time of pregnancy. In addition, we must strengthen the knowledge of the medical profession, especially in the proximity health centers, on rare diseases for a better management of patients.

Phase I INSIGHT platform trial: Advanced safety and efficacy data from stratum D evaluating feasibility and safety of eftilagimod alpha (soluble LAG-3 protein) combined with avelumab in advanced solid tumors.

2518 Background: Stratum D of the INSIGHT platform trial evaluates s.c. eftilagimod alpha (efti, IMP321) combined with avelumab in advanced solid tumors. Efti is an MHC class II agonist which activates antigen-presenting cells followed by CD8 T-cell activation. Combination with PD-1/PD-L1 blockade aims at enhanced efficacy. Methods: This IIT platform trial consists of 5 strata: intratumoral (A) or intraperitoneal efti (B); s.c. efti with SOC (C) or with PD-L1 inhibition (D). Strat E is currently under development and starts soon with a new efti combination. This abstract focuses on preliminary data of Strat D. Patients (pts) received 800mg avelumab i.v. q2w along with s.c. efti: 6mg in cohort 1 (coh 1, 6 pts), 30mg in cohort 2 (coh 2, 6 pts). Primary endpoint: safety. Results: Recruitment has been completed with 12 pts (coh 1: gastric, gallbladder, colon cancer, pleural mesothelioma; coh 2: gastric, gastroesophageal, anal, rectum, cervix uteri). No dose limiting toxicities (DLTs) occurred. 10 serious adverse events (SAEs) were reported, none of them considered causally related (4 in 3 pts of coh 1 [1 acute renal insufficiency grade 5 in 1 pt, 2 preileus grade 3 in 1 pt, hearing impaired grade 4 in 1 pt] and 6 in 4 pts of coh 2 [1 anal hemorrhage and 1 gallbladder obstruction in 1 pt, 1 eye pain and 1 surgery to replace the feeding tube in 1 pt, each grade 3, 1 skin infection grade 2, 1 diffuse myocardial fibrosis grade 5]. 1 AE of special interest (AESI) possibly related with avelumab (sarcoidosis grade 1) occurred in coh 1. 2 pts completed max treatment duration with 24 cycles. In coh 1, 47 adverse events (AEs; grade 1-2, 29; grade 3, 14; grade 4, 3; grade 5, 1) occurred in 5 pts. Most common grade 1-2 AEs were nausea, pain in 33%, 33% of the pts. Most common grade 3 AEs were ileus, vomiting in 33%, 33% of the pts. 2 AEs grade 4 (hearing impaired, sepsis) and 1 AE grade 5 (acute renal insufficiency) were reported. All AEs grade 3-5 were considered causally unrelated. In coh 2, 51 adverse events (AEs; grade 1-2, 29; grade 3, 19; grade 4, 2; grade 5, 1) occurred in 5 pts. The most common grade 1-2 AE was hypothyroidism in 33% of the pts. 1 AE grade 5 (diffuse myocardial fibrosis) was reported. Only 1 AE grade 3-5 was considered causally related (urinary tract infection grade 3 related with avelumab). 5 pts showed partial response as best response (2 coh 1: colon, pleural mesothelioma; 3 coh 2: gastric, anal, cervical), 1 stable disease with clinical progression (coh 2) (all but one of these pts still alive), 5 disease progressions acc. to RECIST 1.1 (3 coh 1, 2 coh 2), 1 clinical progression (coh 1). Signals of activity were also observed in pre-treated MSS/PD-L1low pts. Conclusions: Combined treatment with avelumab 800mg and efti 6mg (coh 1) or 30 mg efti (coh 2) seems feasible and safe. No unexpected AEs occurred. Signals of efficacy with CPI combination were seen (DCR 50%). Clinical trial information: NCT03252938.

ANCA-associated vasculitis overlaps with systemic sclerosis: a case report and literature review

Background Systemic sclerosis (SSc) and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) both affect the kidney and may cause renal failure. Treatment of AAV is dramatically different from that of SSc renal crisis (SRC). Kidney biopsy is not recommended for diagnosing SRC, but it is the only reliable diagnostic method for AAV. Case presentation Here, a 49-year-old male patient with diffuse SSc presented with acute renal insufficiency and detectable ANCA with myeloperoxidase-specific antibodies. A renal biopsy revealed necrotizing glomerulonephritis and was consistent with AAV. This finding confirms the existence of AAV and SSc overlap syndrome. The patient was treated with intravenous methylprednisolone, intravenous cyclophosphamide, tandem membrane plasma exchange, and hemodialysis. After treatment, his clinical symptoms remained stable, and his creatinine and C-reactive protein (CRP) levels have remained normalized as of his most recent follow-up after hospital discharge. Conclusions AAV can overlap with SSc; although this condition is rare, it is associated with considerable morbidity and mortality. Therefore, it is critical to recognize AAV in the setting of worsening renal function due to SSs and provide appropriate treatment. Several clinical features are suggestive of AAV rather than SRC, but renal biopsy is required for accurate diagnosis.

Risk factors for mortality of coronavirus disease-2019 (COVID-19) patients in two centers of Hubei province, China: A retrospective analysis

Purpose Since the outbreak in late December 2019 in Wuhan, China, coronavirus disease-2019 (COVID-19) has become a global pandemic. We analyzed and compared the clinical, laboratory, and radiological characteristics between survivors and non-survivors and identify risk factors for mortality. Methods Clinical and laboratory variables, radiological features, treatment approach, and complications were retrospectively collected in two centers of Hubei province, China. Cox regression analysis was conducted to identify the risk factors for mortality. Results A total of 432 patients were enrolled, and the median patient age was 54 years. The overall mortality rate was 5.09% (22/432). As compared with the survivor group (n = 410), those in the non-survivor group (n = 22) were older, and they had a higher frequency of comorbidities and were more prone to suffer from dyspnea. Several abnormal laboratory variables indicated that acute cardiac injury, hepatic damage, and acute renal insufficiency were detected in the non-survivor group. Non-surviving patients also had a high computed tomography (CT) score and higher rate of consolidation. The most common complication causing death was acute respiratory distress syndrome (ARDS) (18/22, 81.8%). Multivariate Cox regression analysis revealed that hemoglobin (Hb) <90 g/L (hazard ratio, 10.776; 95% confidence interval, 3.075–37.766; p<0.0001), creatine kinase (CK-MB) >8 U/L (9.155; 2.424–34.584; p = 0.001), lactate dehydrogenase (LDH) >245 U/L (5.963; 2.029–17.529; p = 0.001), procalcitonin (PCT) >0.5 ng/ml (7.080; 1.671–29.992; p = 0.008), and CT score >10 (39.503; 12.430–125.539; p<0.0001) were independent risk factors for the mortality of COVID-19. Conclusions Low Hb, high LDH, PCT, and CT score on admission were the predictors for mortality and could assist clinicians in early identification of poor prognosis among COVID-19 patients.

Investigation of the Effect of Pulsatile and Nonpulsatile Flow on Kidney in Coronary Surgery With NIRS

Background: Acute renal insufficiency is a significant cause of morbidity and mortality after coronary artery bypass grafting performed with cardiopulmonary bypass. Functional near-infrared spectroscopy (fNIRS) is an emerging brain-imaging technique that can be used to detect organ perfusions in adults. This study aims to determine the effects of pulsatile and nonpulsatile flow on renal circulation by using functional near-infrared spectroscopy and biochemical markers. Methods: Forty patients, who had undergone isolated CABG between March 2014 and July 2014 in the authors’ clinic, were included in the study. Patients were divided in the pulsatile and nonpulsatile groups by simple randomization. Results: Urine outputs statistically were higher in the pulsatile group, during CPB (P = .045). Renal perfusion measurements via fNIRS intra-operatively statistically were parallel between the groups. When we compared biochemical markers within the groups, in the nonpulsatile group, creatinin statistically is higher on the postoperative first day (P = .003), and BUN statistically is higher on the postoperative first (P = .015), second (P = .001), and fifth (P = .020) days, according to preoperative value. In the pulsatile group, only the postoperative second day BUN is higher (P = .007). Conclusion: fNIRS is being used to track cerebral functions. During operation, it also provides a correct observation for blood feeding of somatic organs, such as the kidneys, but it requires more clinical study to be accepted as routine.

Poikilocytosis under dogs’ spontaneous babesiosis

The article presents the results of studies of changes in the shape of red blood cells during spontaneous babesiosis in dogs. It was found that in 2019, seasonal outbreaks are caused and characterized by the presence of two waves – spring-summer with a peak in June and autumn with a peak in October. The intensity of parasitemia increases synchronously with the extensity of infestation in the first half of the year(a narrow direct correlation), in the future it falls and does not correlate with outbreaks of animal disease. Clinically, the spring-summer wave of the disease is characterized by an acute-subacute typical course with pronounced classic clinical signs. The autumn wave had a predominantly subacute-atypical course, with the development of severe complications with signs of hepatopathy and acute renal insufficiency, cardiomyopathy and myocarditis, lesions of the nervous system, the development of shock with a significant tendency to decompensation. Changes in the shape of red blood cells are bright and indicative markers of the state of animals on babesiosis. Poikilocytosis was detected in 92.3 % of sick dogs. The most common changes are acanthocytosis and vacuolization of erythrocytes (irreversible forms), which qualitatively assess the degree of damage to vital organs. Echinocytes are reversible forms that appear in the early stages and determine the development of renal and hepatic pathologies. Stomatocytes accompany the development of inflammatory and dystrophic pathologies, qualitatively characterize the degree of hemolytic anemia. Their intensity is synchronous with the extent of the invasion. The appearance of schizocytes is a formidable symptom that is pathognomonic for disseminated intravascular coagulation syndrome. This marker requires immediate use of intensive care. The assessment of qualitative changes in the form of red blood cells, the calculation of the intensity of erythrocyte lesions allows you to determine the severity of the condition of the body of sick dogs, the degree of metabolic disorders, hemolytic anemia, hepatopathy, the severity of intoxication, uremic syndrome, spleen hyperplasia, as well as identify the development of DIC syndrome, kidney failure and “shock kidney”. Such an assessment is necessary for making timely and adequate decisions regarding therapeutic measures for spontaneous babesiosis of dogs.

Application of Fasudil in the Treatment of Contrast-Induced Acute Renal Insufficiency Based on Computerized Tomography Intelligent information monitoring (Preprint)

BACKGROUND Background: Contrast-induced acute kidney injury (CI-AKI) is one of the main causes of hospital-acquired acute kidney failure. At present, the exact pathogenesis of CI-AKI is not yet clear. However, the contrast agent reduces renal blood flow and filtration rate, which is its direct toxic effect on renal tubules. Fasudil can relax vascular smooth muscle and act on the kidney, which has a very obvious effect on the expansion of the renal arterioles; also, by adjusting the vascular tone of the microcirculation before and after the glomerulus, it can regulate renal hemodynamics. OBJECTIVE Objective: The objective was to explore the application of Fasudil in the treatment of contrast-induced acute renal insufficiency based on computerized tomography intelligent information monitoring, and explore the application of single-photon emission computerized tomography (SPECT) in the diagnosis of renal insufficiency. METHODS Methods: 32 BALB/C mice were randomly divided into 4 groups, i.e., the renal disease model group (the model group), the renal disease model plus Fasudil high dosage group (the Fasudil high group), the renal disease model plus Fasudil low dosage group (the Fasudil low group), and the control group. After the mice models were grouped, they were banned from drinking water for 12 h. Mice in the model group, the Fasudil high group, and the Fasudil low group were injected with iodixanol injections at a dosage of 4 gI/kg through caudal veins. Mice in the control group were injected with the same dosage of saline. Respectively at 12 h and 2 h before contrast agent injection and 4 h after contrast agent injection, mice in the two Fasudil groups were administered with Fasudil through intraperitoneal injections. The dosage for the Fasudil high group was 10 mg/kg, and the dosage for the Fasudil low group was 10 mg/kg. At the same time nodes, mice in the model group were administered with the same dosage of saline. The histopathological changes in renal tissues, the variations in renal functions, as well as the changes in renal hemodynamics, were observed. RESULTS Results: (1) Compared with the control group, in the model group, the serum creatinine (Cr) and blood urea nitrogen (BUN), as well as the urine N-acetyl-β-D-glucosaminidase (NAG) levels, increased significantly (P<0.05). Compared with the model group, in the Fasudil high group, the serum Cr and BUN, as well as the urine NAG levels, increased significantly (P<0.05). (2) After high-dose fasudil intervention treatment, the destruction of kidney structure in mice was significantly reduced, and the condition of renal tubular epithelial cells swelling was improved. (3) Compared with the control group, in the model group, the RABF values of mice decreased significantly (P<0.05). In the high Fasudil group, after the intervention of high dosed Fasudil, the RABF values of mice increased significantly (P<0.05). CONCLUSIONS Conclusion: The therapy of high-dosage Fasudil for acute renal damages of mice induced by contrast agents could effectively reduce the serum Cr, serum BUN, and urine NAG levels and act as an anti-apoptotic and anti-infective agent. In addition, Fasudil could resist the oxidative stress, thereby improving the contrast agent-induced vasoconstriction responses. The special functional imaging of SPECT can objectively reflect the function of living organs. CLINICALTRIAL