Visceral Damage Research Articles

Evaluation of the diagnostic potential of trans abdominal ultrasonography in detecting intra-abdominal adhesions: A double-blinded cohort study.

BackgroundIntra-abdominal adhesion is one of the most important complications of abdominopelvic surgery. It increases morbidity and mortality for patients. Although laparoscopy is the gold standard of adhesion diagnosis, it can cause visceral damage during the operation. Therefore, surgeons prefer to use non-invasive methods for planning the operation. We designed this study to evaluate transabdominal ultrasonography ( TAU) accuracy for diagnosing Intra-abdominal AdhesionsMaterial & methodsThis double-blinded cohort study was conducted on 47 patients with previous laparotomy who undergo another surgery. Spontaneous visceral slide (SVS) and induced visceral slide (IVS) were measured during TAU.ResultsThe mean age and BMI of 47 patients were 43.21±10.3 and 27.545±5.76. The majority of the patients were female (76%). Mean SVS and IVS in patients with intra-abdominal adhesion were 8.73±1.60 and 44.84±11.60. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of TAU in intra-abdominal diagnosis were 83.33%, 51.72%, 51.72%, 83.33%, 63.83%.ConclusionsAlthough TAU is an appropriate method for detecting the intra-abdominal adhesion, it isn't good enough for diagnosing free adhesion area. We recommended further researches with greater sample size and other non-invasive techniques.

The Wrath of Pancreatic Enzymes: A Rare Case of Hematuria

Acute pancreatitis (AP) is a common gastrointestinal disease associated with many local complications including peripancreatic fluid collections, pseudocysts and necrosis. We present an unusual complication of AP: destruction of the ureter from pancreatic enzymes.A 60-year-old male with a history of former tobacco and alcohol abuse presented to the ED with a 3-day history of periumbilical pain and 1-day of hematuria. Vital signs on admission were within normal limits, physical exam was notable for periumbilical and suprapubic tenderness. Urinalysis showed a significant amount of blood, >100 rbc/hpf, 100mg/dl of protein. Lipase was 259 IU/L. Computed tomography (CT) without contrast showed significant peri-pancreatic stranding around the body and tail of the pancreas with small calcifications in the head. Subsequent CT urogram with contrast showed necrotizing tissue in the body of pancreas, a fluid collection adjacent to the left ureter and evidence of a ruptured left calyx without hydroureteronephrosis. A left ureteral stent and nephrostomy tube were placed. Patients course was complicated by DIC and ARDS, he was discharged 10 days later without any further episodes of hematuria. This case demonstrated multiple complications of severe pancreatitis including a rare manifestation of direct visceral damage. Pancreatic inflammation can have a local effect with involvement of the perirenal fascia in 82% of patients with severe pancreatitis. Release of proteolytic enzymes into the peripancreatic fat is suspected to cause inflammation of the retroperitoneal fascial planes. This local inflammation is noted as perirenal fat stranding on CT imaging. However, progression of this inflammation into direct ureteral damage is exceedingly rare and rupture is usually associated with hydronephrosis and ureteral obstruction. According to a 2009 review, only 27 cases have been reported in the literature. Our case is unique as there is ureteral injury causing rupture but no evidence of hydronephrosis on imaging. Furthermore, the majority of cases with hydronephrosis and ureteral injury are on the right side. Due to the evidence of calcifications in the pancreas on imaging, it is suspected that our patient had acute on chronic pancreatitis causing direct proteolytic injury to the ureter without any concurrent obstruction or hydronephrosis. The case serves as a reminder that two presenting complaints are often correlated to an underlying pathophysiology.1246_A.tif Figure 1: Severe pancreatitis with necrosis1246_B.tif Figure 2: Coronal MIP showing evidence of extravasation of contrast from ureter

Surgical selection and outcome for treating the post-traumatic posterior urethral strictures via transperineal approach

Objective To evaluate the outcome of various operative selection for treating posterior urethral stricture via transperineal approach. Methods The clinical data of 5 000 patients with posterior urethral stricture or obstruction from January 1990 to January 2017 were analyzed retrospectively. All patients were male. The age of those patients ranged from 18 months to 77 years old, mean 36.6 years old. Pelvic crush injury caused by car accident occurred in 2010 cases. Falling injury occurred in 1680 cases. Pelvic compressed injury occurred in 1 310 cases. Accompanied visceral damage occurred in 2 590 cases, including the liver and spleen rupture in 920 cases, lower limb fracture in 1 200 cases. 2 200 cases accepted urethral realignment under emergency. 2 800 cases were treated with pubic cystostomy. All patients were undergone a retrograde and voiding urethrogram. 562 patients accepted urethral ultrasongraphy, and 2 448 patients accepted urethroscopy. 204 patients accepted MRI examination. The mean stricture length was 4.3 cm, ranged from 1.8 to 8.6 cm. Posterior urethral stricture was found in 810(16.2%)cases. The complete obstruction of posterior urethra was found in 4 190(83.8%)cases, of which the length of the distraction defects≤3 cm was found in 2 650(53.0%)cases and the length of the distraction defects>3 cm was found in 1 540(30.8%)cases. Bladder calculi was found in 2 300 cases. The perineal fistula or abscess was noticed in 290 cases. False passage was found in 460 cases. Urethra rectum fistula was found in 160 cases. Bladder neck open was noticed in 89 cases. Repairing was performed via a simple anastomosis after urethral mobilization in 1 700 patients, via separation of the corporeal bodies in 1 302 patients, via separation of the corporeal bodies and inferior pubectomy in 1 910 patients and via scrotal skin flap urethroplasty in 68 patients. Pull-through operation was performed in 20 patients. Results Postoperative follow-up were conducted from 6 to 72 months with average duration of 23 months. The overall successive results after operation was 92.2%(4 608/5 000), which the Qmax was more than 15 ml/s .The successive rate of urethroplasty were 97%(1 649/1 700 )in simple anastomosis; 93%(1 211/1 302 )in separation of the corporeal bodies; 88% (1 680/1 910) in separation of the corporeal bodies and inferior puberctomy; 78%(53/68) in scrotal skin flap urethroplasty and 83%(15/18) in pull-through operation. The successive rate were 96%(778/810)in posterior urethral stricture; 95%(2 517/2 650)in distraction with the length of obstruction less than 3 cm and 86%(1 324/1 540)in distraction with the length of obstruction more than 3 cm. Conclusions The transperineal end to end anastomotic urethroplasty has become the first-line therapy for posterior urethral atresia. The length of the strictures or distraction defect which is lower than 3 cm is much more successfully corrected. Key words: Urethral stricture; Urological surgical procedure; Transperineal; Wound and injuiry

Abstract P350: Early Signs of Stress Induced Arterial Hypertension During Cardiopulmonary Testing and Advantages in Cardiac Risk Lowering

Goal: to study early signs and hypertension reaction features during cardiopulmonary exercise testing (CPET) in intellectually working men with rare episodes of stress induced blood pressure (BP) increase. Methods: 47 patients (pats) with periodic episodes of high BP due to high level of stress were included (all men, 42 ± 4.6 years old). Risk factors: smoking had 83% of pats, high cholesterol level 87%, glucose intolerance 39%, family history of high BP 14%. All pats had normal BMI and no signs of visceral fat and target organ damage, 54% used hypotensive therapy non-systemically, 98% complained for sleep disorders. CPET was done for optimal training regime appointment. Baseline BP was 134± 2,8 mm Hg. Most of the pats demonstrated low physical tolerance level (6,7±0.4 MET). All patients demonstrated hypertensive reaction during test, and that was the reason for test stop. 68% of pats demonstrated systolic BP 220 mm Hg at respiratory compensation point (RCP) and RER 1,17 ± 0.01, 32% of pats demonstrated it earlier than RCP and at RER 0.85± 0.06. All pats got recommendations with optimal physical and pulse regime for training. All the patients had 3 ± 1 moderate intensive aerobic training per week for 34 ± 10.7 min. Results: in 6 months all the patients demonstrated increase in physical tolerance (ΔVO2 5,3 ±1,3 ml/kg/min). Patients with hypertension reaction at RCP showed significantly lower baseline BP (124.6± 3.5mm Hg vs 131.2 ± 4.1 mm Hg in other patients, p <0.05), only 14% demonstrated hypertensive reaction during CPET vs 89% in other patients, p <0.05 and mentioned less hypertension episodes during 6 months (7 ± 3 episodes vs 24 ± 2, p <0.05). 96% pats of this group demonstrated higher level of physical tolerance (load 9,8 ± 0.3 MET vs 7.6± 1.1 MET, p <0,05). Also, they didn't show abnormalities in glucose intolerance test. Conclusion: hypertension reaction at RCP during CPET in intellectually working man with episodic stress induced increase of blood pressure can be a predictor of great benefit in life style modification, cardiac risk lowering and arterial hypertension control

RHEUMATOID ARTHRITIS: THE PROBLEMS OF REMISSION AND THERAPY RESISTANCE

Rheumatoid arthritis (RA) is an immunoinflammatory (autoimmune) rheumatic disease of unknown etiology, which is characterized by chronic erosive arthritis and systemic visceral organ damage that results in early disability and shorter patient survival. Despite RA treatment advances associated with the design of novel drugs and the improvement of treatment strategies to achieve remission in many patients, there are still many theoretical and clinical problems concerning both the definition of the concept of remission, its characteristics and types and approaches to the optimum policy of symptomatic and pathogenetic drug therapy at different stages of the disease, the use of which will be able to rapidly induce and maintain remission in the long-term. Further investigations are needed to study the nature of heterogeneity of pathogenetic mechanisms of RA and approaches to early diagnosis, to improve methods for monitoring disease activity and biomarkers for the efficiency of and resistance to therapy and, finally, to develop differentiation therapy, including those related to a search for new therapeutic targets.

Chinese expert consensus on echelons treatment of pelvic fractures in modern war

The characteristics and treatment of pelvic fractures vary between general conditions and modern war. An expert consensus has been reached based on pelvic injury epidemiology and the concepts of battlefield treatment combined with the existing levels of military medical care in modern warfare. According to this consensus, first aid, emergency treatment and early treatment of pelvic fractures are introduced in three separate levels. In Level I facilities, simple triage and rapid treatment following the principles of advanced trauma life support are recommended to evaluate combat casualties during the first-aid stage. Re-evaluation, further immobilization and fixation, and hemostasis are recommended at Level II facilities. At Level III facilities, the main components of damage control surgery are recommended, including comprehensive hemostasis, a proper resuscitation strategy, the treatment of concurrent visceral and blood vessel damage, and battlefield intensive care. The grading standard for evidence evaluation and recommendation was used to reach this expert consensus.

Forensic Aspects in Polonium-210 Poisoning

The human body is exposed to radiation resulting from the presence and degradation in the environment of natural radionuclides like uranium and thorium. In laboratories, several radioactive isotopes are being used: uranium-235, iodine-131, cobalt-60, and carbon-14. These radioactive isotopes are useful in scientific (dating human skeletal remains) and medical purposes (radiotherapy/radiodiagnosis), but they are also used in criminal context. Polonium 210 (Po-210) is a natural radioisotope occurring in the natural environment as consequence of uraniu-238 decay chain. The current paper presents a less known subject of lethal poisoning with Po-210 radioisotope, in order to underline the methods used for Po-210 identification in forensic samples. The authors performed a literature review of the scientific researchers published in the last years concerning polonium sources and its use as a poison. Polonium�s effectiveness as a poison relies on its chemical characteristics only to the extent that they determine the isotope�s distribution and retention in organs and tissues; the alpha particles are responsible for the lethal effect. Po-210 poisoning is particular, as it doesn�t leave traces, it can be easily transported, and is not detected by airport scanners. Identifying this compound during a medico-legal autopsy is very difficult, as the post-mortem examination will not yield characteristic aspects, the forensic pathologist being forced to consider this as a potential cause of a rapid death, with significant visceral damage.

Epidemiological, clinical, diagnostic and economic features of an immigrant population of chronic schistosomiasis sufferers with long-term residence in a non-endemic country (North Metropolitan area of Barcelona, 2002-2016).

BackgroundSchistosomiasis, one of the neglected tropical diseases (NTD) listed by the WHO, is an acute and chronic parasitic disease caused by blood flukes (trematode worms) of the genus Schistosoma. Complications of long-term infestation include liver cirrhosis, bladder tumors and kidney failure. The objective of this study was to carry out a clinical and epidemiological characterization of a schistosomiasis-diagnosed immigrant population with long-term residencein the EU as well as to evaluate the diagnostic methods available to date.Methods and resultsA total of 61 individuals with Schistosoma infection who received medical attention between June 2002 and June 2016 at the North Metropolitan International Health Unit in Barcelona (Catalonia, Spain), were included in the study. All patients were sub-Saharan African immigrants. The majority were male (91.8%) with a median age of 34 years. Symptoms attributable to infection such as haematuria, abdominal pain and dysuria were recorded in up to 90% of patients. The percentage of eosinophils decreased amongst older patients (p = 0.002) and those with symptoms associated with urinary tract infections (p = 0.017). Serology was used for diagnosis in 80.3% of the cases, with microscopic examination showing the remaining 9.8% positive for parasite eggs. Direct microbiological diagnosis was more useful in patients with less than 5 years of residence in the EU (p = 0.05). Chronic complications were present in 22 (36%) of the patients, with renal failure affecting 20 (33%). Of these 20, 6(10%) developed terminal renal failure and required hemodialysis, while 3 (5%) received a renal transplantation.ConclusionMorbidity associated with chronic long-term schistosomiasis is frequent among African immigrants in non-endemic countries. Better diagnostic tools and appropriate early treatment would prevent the development of visceral damage. Thorough screening in selected patients would also be useful to avoid chronic complications.

Complement levels and risk of organ involvement in patients with systemic lupus erythematosus

ObjectiveComplement plays a major role in SLE. Complement participation has been linked to disease activity and damage. Our objective was to estimate the association of complement behaviour with clinical manifestations,...

Retrospective Analysis of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in 88 Chinese Patients.

Background:Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening diseases with high mortality rates. This study was designed to analyze the pathogenic factors, clinical manifestations, complications, treatment, and prognosis of SJS/TEN and to explore the differences between surviving and deceased patients.Methods:SJS/TEN patients admitted to Beijing Friendship Hospital from January 2006 to December 2015 were included in the study. Patients’ data were retrospectively analyzed. Comparative studies were performed on the survival group and the deceased group, and Fisher's exact probability test was used for statistical analysis.Results:Among the 88 patients included, 40 (45.5%) were male with a mean age of 45 ± 18 years. Forty-eight (54.5%) had SJS, 34 (38.6%) had SJS/TEN, and 6 (6.8%) had TEN. Fifty-three (60.2%) cases were caused by medications, mainly antibiotics (n = 24) followed by traditional Chinese medicines (n = 7). Forty-two cases (47.7%) developed visceral damage. Eighty-two patients improved or recovered and were discharged from hospital, and six patients died. Comparative studies on the survival group and the deceased group showed that the presence of malignant tumor (χ2 = 27.969, P < 0.001), connective tissue diseases (χ2 = 9.187, P = 0.002), previous abnormal liver/kidney functions (χ2 = 6.006, P = 0.014), heart rate >100 times/min (χ2 = 6.347, P = 0.012), detached skin area >20% (χ2 = 5.594, P = 0.018), concurrent mucosal involvement at the mouth, eyes, and external genitals (χ2 = 4.945, P = 0.026), subsequent accompanying liver/kidney damage (χ2 = 11.839, P = 0.001, and χ2 = 36.302, P < 0.001, respectively), and SCORTEN score >2 (χ2 = 37.148, P < 0.001) increased the risk of death.Conclusions:SJS/TEN is mainly caused by medications, and nearly half of patients develop visceral damage. Multiple factors increase the mortality risk.

Severe scorpion envenomation: pathophysiology and the role of inflammation in multiple organ failure.

Scorpion stings occur on every continent except Antarctica. The correlation between young age and severity of clinical manifestations after this envenomation is well-established. Several studies have emphasized the relevance of pro-inflammatory mediators in the pathophysiological manifestations of human scorpion envenomation. Moreover, there is a significant association between pro-inflammatory cytokine levels in the blood and the severity of scorpion envenomation. Release of these cytokines increases the severity of the visceral damage induced by the direct action of the venom and the activation of both the sympathetic and parasympathetic nervous systems.

Drug Reaction with Eosinophilia and Systemic Symptoms: Retrospective Analysis of 104 Cases over One Decade.

Background:Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, life-threatening disorder caused by drugs. In the present study, we tried to explore the types of DRESS-inducing drugs, incubation period, features of skin rashes, accompanying visceral damage, and effectiveness of glucocorticoid therapy so as to inform clinical practice.Methods:Patients diagnosed with a drug-induced rash, dermatitis, and DRESS admitted to our hospital from January 2006 to December 2015 were included in the study. The diagnosis followed the criteria and scoring system set by the European Registry of Severe Cutaneous Adverse Reactions. Statistical analyses were carried out using SPSS version 17.0 (IBM, Armonk, NY, USA), and a value of P < 0.05 was considered statistically significant.Results:Among 104 patients, 38 were male and 66 female (aged 18–83 years). The latent period was 13 (interquartile range [IQR]: 10–17) days. The most common allergy-inducing drugs were antibiotics (n = 37, 35.6%), followed by antiepileptic drugs and traditional Chinese medicines (TCMs). Eighty-two cases (78.8%) had rash with area >50% body surface area (BSA). Liver damage occurred in 90% of cases. Patients were divided into oral antihistamine group and glucocorticoid/immunosuppressive agent/intravenous immunoglobulin (IVIG) group. Sex, age, incubation period, duration of hospital stay, and the number of patients with body temperature ≥38.5°C were not significantly different between the two groups. However, the number of patients meeting the criteria of “definite” and “probable” (χ2 = 5.852, P = 0.016), with an eosinophilic granulocyte count of ≥1.5 × 109/L (χ2 = 7.129, P = 0.008), and with rash area of >50% BSA (χ2 = 4.750, P = 0.029), was significantly different.Conclusions:Antibiotics were associated with allergic reactions, but TCMs also had an important role. Allergy resulting from repeat use of the same drug was more severe with a shorter incubation period. The most typical rash was widespread erythematous papules. Liver damage accounted for >90% of cases.

Anticoagulation Alone for Aortic Segment Treatment in Symptomatic Primary Aortic Mural Thrombus Patients

Primary aortic mural thrombus (AMT) is a rare entity. Asymptomatic AMT may be found in imaging studies for other disease studies. Symptomatic AMT as embolic events may localize in the arterial branches of the aorta; limb ischemia is the most usual clinical presentation, though. However, when proximal aorta is compromised, visceral branches occlusion and ischemia may determine morbidity and mortality in these patients. We performed a retrospective study with collection of data from January 2011 to September 2016. Medical records of patients were reviewed for: demographic data, cardiovascular risk factors or any known prothrombotic predisposing condition, clinical presentation, vessel of embolism, localization of aortic thrombus, treatment of AMT and symptoms, follow-up, and computed tomography scan imaging findings. A total of 8 patients were included in the study. Mean age was 54.7±11.5years, with male/female ratio 3:1. Four (50%) patients had AMT at the arch or descending aorta, 3 (37.5%) patients in the infrarenal sector, and the remaining in the visceral aorta. All but one patient received anticoagulation alone for the aortic thrombus. Patient with femoral thromboembolectomy died in the early postoperative time due to severe massive embolism. Median follow-up was 23months (range, 1-50). Five out of seven patients showed complete aortic thrombus resolution in imaging follow up. None of the patients presented recurrence of embolic events. An anticoagulation first-approach treatment may be reasonable if mild organ damage is encountered. This strategy may be continued if no recurrences in embolic events are encountered, as high percentage of thrombus resolution is expected. Open or endovascular may be saved for life-threatening visceral or arch branches damage.

Newborn screening for mucopolysaccharidoses: a pilot study of measurement of glycosaminoglycans by tandem mass spectrometry

Background Mucopolysaccharidoses (MPS) are a group of inborn errors of metabolism that are progressive and usually result in irreversible skeletal, visceral, and/or brain damage, highlighting a need for early diagnosis.

Reconstruction of Vertebral Body After Radiofrequency Ablation and Augmentation in Dorsolumbar Metastatic Vertebral Fracture: Analysis of Clinical and Radiological Outcome in a Clinical Series of 18 Patients.

Painful spinal metastases usually occur in malignant neoplastic disease. Treatment for bone metastases has been largely conservative, and it includes the use of high doses of analgesics, radiotherapy, chemotherapy, hormone therapy, and bisphosphonates; however, results are sometimes transient and ineffective. In the presence of neurological involvement a surgical strategy should be considered. Recently, percutaneous procedures such as radiofrequency ablation, vertebroplasty, and kyphoplasty have been introduced as palliative techniques to treat painful vertebral metastases [3, 11, 25]. In our study we combined the use of radiofrequency ablation with vertebroplasty in the treatment of dorsolumbar metastatic vertebral fractures in order to examine the relationship between restoration of the vertebral structure and decrease in pain. From January 2014 to March 2015 we retrospectively analyzed 18 patients with malignant vertebral lesions who underwent radiofrequency ablation with vertebroplasty followed by cementoplasty, with posterior transpedicle fixation on levels near the lesions. The parameters examined were: demographics, pain relief, and the distribution of polymethylmethacrylate (PMMA) determined by the mean Saliou filling score; all complications were recorded. The mean age of the patients was 55.72 years (range 34-69); average operative time was 60.4 min (range, 51-72). The average pain index score (visual analog score; VAS) decreased significantly from 8.05 at baseline to 3.0 (p < 0.05) after 6 months. The Saliou filling score revealed a distribution of PMMA in the vertebral body that was satisfactory (12-18) in eight patients, mediocre (6-12) in seven patients, and inadequate (0-6) in the remaining three patients. In two vertebrae, minimal asymptomatic cement leakage occurred in the lateral recess without neurological damage. No pulmonary embolism and no visceral or neural damage was recorded. Radiofrequency ablation combined with vertebroplasty seems to achieve rapid and lasting improvement in clinical symptoms in patients with malignant vertebral lesions. There was wide diffusion of PMMA in the vertebral body, with a mean cement volume of 4.5 ml.

Abdominal penetrating trauma and organ damage and its prognosis

Introduction: Abdominal penetrating trauma is still a serious problem in the world, due to its high prevalence in young people that impose a heavy economic burden on our country, we decided to evaluate the epidemiologic and demographic status and patient’s prognosis. Methods: This is a descriptive cross-sectional study; all patients with abdominal penetrating trauma referred to the emergency department of Imam Reza Hospital between March 2012 and March 2014 were enrolled to study. Age, sex, injured organs, mechanism of trauma and the prognosis was documented in the checklist. Data was analyzed by SPSS 15.0, and descriptive analysis was run. Results: In this study, 137 patients were enrolled; 103 patients (75.20%) did not have visceral damage. In visceral injury, the spleen was most commonly injured abdominal organs (8.03%). the damage to small intestine seen in 8 patients (5.84%), kidney and liver damage seen in 6 patients (4.38%) and 5 patients, respectively, and finally diaphragm and colon injury was seen in 2 patients (1.46%). Conclusion: According to a recent study, abdominal penetrating trauma mostly occurred in men. The most common cause of abdominal penetrating trauma was related to knife damage; spleen was commonly damaged organ caused by knives and other sharp objects.

Improved Control of GvHD with Rabbit ATG, Rituximab and Bortezomib Among Pediatric Leukemia Patients after Tcrαβ/CD19-Depletion of Transplant from Matched Unrelated and Haploidentical Family Donors: A Single-Center Retrospective Analysis of Two Gvhd-Prophylaxis Regimens

Introduction:Graft-versus-host disease (GvHD) remains to be a factor associated with significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Bortezomib was shown in vitro to induce selective depletion of alloreactive T-lymphocytes, decrease the production of Th1 cytokines (Blanco et al. 2006), and to suppress the maturation and cytokine production by dendritic cells (Naujokat et al. 2007). Bortezomib was successfully used to prevent and treat GVHD in different settings (Al-Homsi et al. 2015; Koreth et al. 2015). As GvHD-prophylaxis agent Bortezomib was implemented since 2014 in aim to improve the results in a cohort of pediatric patients with acute leukemia who underwent HSCT from HLA-matched unrelated and haploidentical family donors after TCRαβ/CD19-depletion. Here we present the results of a retrospective comparison of two GvHD-prophylaxis regimens.Patients and methods:Between May 2012 and July 2016 eighty-one transplantation from 40 HLA-matched unrelated and 41 haploidentical donors were performed for children (56 boys and 25 girls with median age 9 years, range 0,6-23 years) with acute lymphoblastic (n=31) and acute myeloblastic (n=50) leukemia in complete remission. TCRαβ/CD19-depletion of HSC with CliniMACS technology was implemented in all cases. For all patients it was first allogeneic HSCT.The majority (93%) of the patients received Treosulfan-based condition regimen. Remaining 7% of patients received TBI-based conditioning regimen.Patients were divided retrospectively in two groups according to GvHD prophylaxis regimens. "Regimen 1" (n=35), which was used in 2012-2013 yrs.: horse ATG 50 mg/kg and post-transplant tacrolimus with short course of methotrexate. "Regimen 2" (n=46) started in 2014: rabbit ATG 5 mg/kg, rituximab 200mg/m2 and peri-transplant bortezomib 1,3 mg/m2 on days -5, -2, +2 and +5. The median dose of CD34+ cells in the transplant was 9 x106/kg (range 7-17), TCRαβ - 21x103/kg (range 1-305).Results:Groups differed significantly in regards to diagnosis: 57% of patients in "Regimen 1" had ALL, while most of the patients (78%) in "Regimen 2" were with AML (P= 0,002).Cumulative incidence of neutrophil and platelet engraftment at 30 days was 98% and did not differ between the groups. Median time to neutrophil and platelet engraftment was 14 days, (range, 9-33 and 9-25 days, respectively). Neutrophil engraftment was significantly faster among patients with "Regimen 2", 13 days vs. 16 days for patients with "Regimen 1" and CI of engraftment at day 30 after HSCT 98% (95% CI: 98%) vs. 94% (95% CI: 87-100, P<0,01).Overall cumulative incidence of acute GvHD II-IV grade was 23% (95% CI: 16-35); grade III-IV - 5% (95% CI: 2-13) and chronic GvHD - 18% (95% CI: 11-20). Cumulative incidence of acute GvHD II-IV was significantly lower within the group with "Regimen 2": 15% (95% CI: 7-30) vs. 34% (95% CI: 22-54), P=0,05. Amid patients with "Regimen2" there was one case of grade IV acute GvHD, most of the patients with grade II to IV developed visceral damage involving lower gut. "Regimen 2" was also more effective in prevention of chronic GvHD: CI at 1 year after HSCT was 7% vs. 31%, P=0,005. Only one patient with "Regimen 2" had extensive form of chronic GvHD.Median time of follow-up for survivors was 2 years (range, 0,3 - 4). Cumulative incidence of relapse at 2 years also differed between "Regimen 1" and "Regimen 2" groups, 31% (95% CI: 19-51) vs. 21% (95% CI: 11-39), respectively, though without statistical significance. TRM was 10% (95% CI: 5-20), without significant statistical difference between leukemia type, donor type or GvHD-prophylaxis regimens. EFS (event=death or relapse) at 2 years was 64% (95%CI: 53-75), OS - 69% (95%CI: 58-80). Statistically there was no significant difference in event-free or overall survival probabilities between leukemia type, donor type or GvHD-prophylaxis regimensConclusion:In our retrospective single-center study we revealed that rATG, rituximab and bortezomib improve the control of acute and chronic GVHD in recipients of TCRαβ- depleted grafts in comparison to hATG, tacrolimus and methotrexate. DisclosuresNo relevant conflicts of interest to declare.

Carotid Catheterization and Automated Blood Sampling Induce Systemic IL-6 Secretion and Local Tissue Damage and Inflammation in the Heart, Kidneys, Liver and Salivary Glands in NMRI Mice.

Automated blood sampling through a vascular catheter is a frequently utilized technique in laboratory mice. The potential immunological and physiological implications associated with this technique have, however, not been investigated in detail. The present study compared plasma levels of the cytokines IL-1β, IL-2, IL-6, IL-10, IL-17A, GM-CSF, IFN-γ and TNF-α in male NMRI mice that had been subjected to carotid artery catheterization and subsequent automated blood sampling with age-matched control mice. Body weight and histopathological changes in the surgical area, including the salivary glands, the heart, brain, spleen, liver, kidneys and lungs were compared. Catheterized mice had higher levels of IL-6 than did control mice, but other cytokine levels did not differ between the groups. No significant difference in body weight was found. The histology revealed inflammatory and regenerative (healing) changes at surgical sites of all catheterized mice, with mild inflammatory changes extending into the salivary glands. Several catheterized mice had multifocal degenerative to necrotic changes with inflammation in the heart, kidneys and livers, suggesting that thrombi had detached from the catheter tip and embolized to distant sites. Thus, catheterization and subsequent automated blood sampling may have physiological impact. Possible confounding effects of visceral damage should be assessed and considered, when using catheterized mouse models.

Newborn screening for mucopolysaccharidoses: a pilot study of measurement of glycosaminoglycans by tandem mass spectrometry.

Mucopolysaccharidoses (MPS) are a group of inborn errors of metabolism that are progressive and usually result in irreversible skeletal, visceral, and/or brain damage, highlighting a need for early diagnosis. This pilot study analyzed 2862 dried blood spots (DBS) from newborns and 14 DBS from newborn patients with MPS (MPS I, n = 7; MPS II, n = 2; MPS III, n = 5). Disaccharides were produced from polymer GAGs by digestion with chondroitinase B, heparitinase, and keratanase II. Heparan sulfate (0S, NS), dermatan sulfate (DS) and mono- and di-sulfated KS were measured by liquid chromatography tandem mass spectrometry (LC-MS/MS). Median absolute deviation (MAD) was used to determine cutoffs to distinguish patients from controls. Cutoffs were defined as median + 7× MAD from general newborns. The cutoffs were as follows: HS-0S > 90ng/mL; HS-NS > 23ng/mL, DS > 88ng/mL; mono-sulfated KS > 445ng/mL; di-sulfated KS > 89ng/mL and ratio di-KS in total KS > 32%. All MPS I and II samples were above the cutoffs for HS-0S, HS-NS, and DS, and all MPS III samples were above cutoffs for HS-0S and HS-NS. The rate of false positives for MPS I and II was 0.03% based on a combination of HS-0S, HS-NS, and DS, and for MPS III was 0.9% based upon a combination of HS-0S and HS-NS. Combination of levels of two or more different GAGs improves separation of MPS patients from unaffected controls, indicating that GAG measurements are potentially valuable biomarkers for newborn screening for MPS.

Understanding Toxoplasmosis in the United States Through "Large Data" Analyses.

Toxoplasma gondii infection causes substantial morbidity and mortality in the United States, and infects approximately one-third of persons globally. Clinical manifestations vary. Seropositivity is associated with neurologic diseases and malignancies. There are few objective data concerning US incidence and distribution of toxoplasmosis. Truven Health MarketScan Database and International Classification of Diseases, Ninth Revision (ICD-9) codes, including treatment specific to toxoplasmosis, identified patients with this disease. Spatiotemporal distribution and patterns of disease manifestation were analyzed. Comorbidities between patients and matched controls were compared. Between 2003 and 2012, 9260 patients had ICD-9 codes for toxoplasmosis. This database of patients with ICD-9 codes includes 15% of those in the United States, excluding patients with no or public insurance. Thus, assuming that demographics do not change incidence, the calculated total is 61 700 or 6856 patients per year. Disease was more prevalent in the South. Mean age at diagnosis was 37.5 ± 15.5 years; 2.4% were children aged 0-2 years, likely congenitally infected. Forty-one percent were male, and 73% of women were of reproductive age. Of identified patients, 38% had eye disease and 12% presented with other serious manifestations, including central nervous system and visceral organ damage. Toxoplasmosis was statistically associated with substantial comorbidities, including human immunodeficiency virus, autoimmune diseases, and neurologic diseases. Toxoplasmosis causes morbidity and mortality in the United States. Our analysis of private insurance records missed certain at-risk populations and revealed fewer cases of retinal disease than previously estimated, suggesting undercoding, underreporting, undertreating, or differing demographics of those with eye disease. Mandatory reporting of infection to health departments and gestational screening could improve care and facilitate detection of epidemics and, thereby, public health interventions.