Impact of immune-mediated diseases in inflammatory bowel disease and implications in therapeutic approach.

Inflammatory bowel diseases (IBD) belong to the group of immune-mediated diseases (IMIDs). The effect of associated IMIDs in the prognosis in IBD is nowadays unknown. To describe IMIDs associated to IBD patients and evaluate differences linked to the presence or absence of IMIDs. A unicentric retrospective descriptive study was designed. A cohort of 1,448 patients were categorized according to the presence of IMIDs. Clinical characteristics were obtained from IBD database. Univariate and multivariate analysis were performed. 385 patients were diagnosed with associated IMIDs while 1,063 had no associated IMIDs. A prevalence of 26.6% IMIDs associated to IBD was observed. Asthma, skin psoriasis and rheumatoid diseases were most commonly found. Factors associated to the presence of IMIDs were women (OR 1.48; 95 CI 1.17-1.87) and Crohn's disease (OR 1.35; 95 CI 1.07-1.70). Patients with associated IMIDs required more immunomodulator (OR 1.61; 95 CI 1.27-2.43) and biological treatment (OR 1.81; 95 CI 1.47-2.43). More surgical risk was observed in multivariate analysis in those patients diagnosed with IMIDs prior to the onset of IBD (OR 3.71; 95% CI 2.1-6.56). We considered the presence of IMIDs a poor prognostic factor and suggest a closer monitoring of these patients.

Multivariate analysis on complications of central venous access devices in children with cancer and severe disease influenced by catheter tip position and vessel insertion site (A STROBE-compliant study).

CONTEXT: Reliable long-term central venous access device (CVAD) is essential for the management of pediatric patients with cancer or chronic diseases. However, there is no general consensus for optimal catheter tip location and vessel insertion site in children. OBJECTIVE: This single center study analyzes the risk of complications associated with long-term upper body CVAD and evaluates them with respect to catheter tip location as well as vessel insertion site. DESIGN: Pediatric patients who received long-term upper body CVAD from January 2008 through April 2017 and underwent radiographic documentation of the tip location were retrospectively included in the study. Data on demographics, catheter tip location on chest x-ray, intraoperative vessel insertion sites and postoperative complications were analyzed. Catheter tip location was categorized as "high" (above the right mainstem bronchus), "medium" (at the level of the bronchus), and "low" (below the right mainstem bronchus). Distance to the carina was measured as well. RESULTS: A total of 396 patients, 74.7% suffering from cancer were included in our study (mean age 6.3 ± 0.3 years). Complications occurred in about one fourth of all patients. Catheter-related blood stream infections (BSI) (n = 40, 36.4%) were most prevalent, but catheter tip position or vessel insertion site had no impact on the risk of infections. Dislodgement (n = 27, 24.6%) and occlusion (n = 11, 10.0%) were more frequent in "high" positioned catheter tips. While there was one patient who developed arrhythmia, no case of cardiac perforation, and in particular, no catheter-related death was recorded in our series. The vessel insertion site seemed to have no influence on the complication frequency of CAVDs. CONCLUSION: The catheter tip position seems to have an impact on the catheter-related complication profile in children. To avoid complications, we recommend avoiding a "high" localization of the catheter tip above the right main bronchus. "Low" catheter tip placement was associated with the lowest dislocation rate. Given the overall low complication rate, insertion and use of CVADs in children can generally be considered as safe.

The Role of Histone Methyltransferases and Long Non-coding RNAs in the Regulation of T Cell Fate Decisions.

T cell lineage decisions are critical for the development of proper immune responses to pathogens as well as important for the resolution of inflammatory responses. This differentiation process relies on a combination of intrinsic and extrinsic factors converging upon epigenetic regulation of transcriptional networks relevant to specific T cell lineages. As these biochemical modifications represent therapeutic opportunities in cancer biology and autoimmunity, implications of writers and readers of epigenetic marks to immune cell differentiation and function are highly relevant. Given the ready adoption of histone methyltransferase inhibitors in the clinic, we focus this review on the role of three histone modifying complexes: PRC-1, PRC-2, and G9A in modulating T cell fate decisions. Furthermore, we explore the role of long non-coding RNAs in regulating these processes, and discuss recent advances and challenges of implementing epigenetic therapies into clinical practice.

IgG4-related sclerosing mesenteritis, a rare condition that causes abdominal pain.

The identification of IgG4-related disease as a distinct immune-mediated condition encompassing disorders that were traditionally seen as idiopathic has been a revolution in the diagnostic and therapeutic algorithm in several medical fields. This condition usually involves multiple organs (isolated organ involvement is uncommon except in the pancreas) with characteristic histopathological findings. We report a case that was assessed due to abdominal pain and subsequently diagnosed with IgG4-related sclerosing mesenteritis. A comprehensive work-up of the case ruled out other conditions and a diagnosis of IgG4-related sclerosing mesenteritis was made according to radiographic and histopathological criteria.

Mycobacterium genavense-induced spindle cell pseudotumor in a pediatric hematopoietic stem cell transplant recipient: Case report and review of the literature.

We describe the first reported pediatric patient to our knowledge with a spindle cell pseudotumor caused by Mycobacterium genavense in a hematopoietic stem cell transplant recipient, and review the literature of such an entity in the transplant population.

Laparoscopic-assisted splenectomy in dogs: 18 cases (2012-2014).

OBJECTIVE: To describe the operative technique and perioperative outcome for laparoscopic-assisted splenectomy (LAS) in dogs. DESIGN: Retrospective case series. ANIMALS: 18 client-owned dogs. PROCEDURES: Medical records of dogs with naturally occurring disease of the spleen treated by means of LAS between 2012 and 2014 were reviewed. History, signalment, results of physical examination, results of preoperative diagnostic testing, details of surgical technique, intraoperative findings including results of abdominal exploration and staging, concurrent surgical procedures, complications, histopathologic diagnoses, duration of postoperative hospitalization, and perioperative outcome were recorded. The perioperative period was defined as the time from hospital admission for LAS until discharge or death (within the same visit). RESULTS: All dogs underwent initial abdominal exploration and staging via multiple 5-mm laparoscopic ports (n = 2) or a single commercially available multichannel port (16), followed by minilaparotomy with insertion of a wound retraction device, progressive exteriorization of the spleen, sealing of hilar vessels, and splenectomy. Splenectomy was performed for treatment of a splenic mass (n = 15), suspected neoplasia (2), or refractory immune-mediated disease (1). Median size (width × length) of splenic masses was 5 × 5 cm (range, 1.6 to 11.0 cm × 1.5 to 14.5 cm). Complications were limited to minor intraoperative hemorrhage in 1 dog; no patient required conversion to open laparotomy. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that LAS was technically feasible in dogs and not associated with major complications. Further evaluation is required; however, in appropriately selected patients, LAS may offer the benefits of a minimally invasive technique, including a smaller incision and improved illumination and magnification during exploration and staging.

C5b-9 deposits on endomysial capillaries in non-dermatomyositis cases.

Deposits of the terminal-membrane-attack-complex (MAC) C5b-9 on perfascicular endomysial capillaries are generally regarded as diagnostic hallmark of dermatomyositis (DM). Although the pathophysiology is not clear, C5b-9 deposits on capillaries seem to be associated with microinfarctions and vascular damage. Here, we report on a series of 19 patients presenting with C5b-9 accumulation on endomysial capillaries in the absence of features for DM. To decipher differences in the capillary C5b-9 accumulation pattern between DM and non-DM cases, we assessed the extent of endomysial capillary C5b-9 deposits related to capillary density and extent of myofiber necrosis by immunohistochemistry in 12 DM and 8 control patients. We found similar numbers of C5b-9-positive myofibers in both DM and non-DM C5b-9(+) cases. The distribution pattern differed as DM cases showed significantly more perifascicular capillary C5b-9 deposits as compared to non-DM cases, which presented stronger endomysial capillary C5b-9 deposits in a diffuse pattern. While total capillary density was not differing, DM patients displayed significantly more C5b-9(+) necrotic fibers as compared to non-DM C5b-9(+). In summary, endomysial capillary C5b-9 deposits are present in a variety of non-DM cases, however with differing distribution pattern. In conclusion, capillary C5b-9(+) deposits should be assessed critically, taking into consideration the distribution pattern.

Immunomodulatory properties of mesenchymal stem cells and their therapeutic applications.

Mesenchymal stem cells (MSCs) are adult stem cells that can be isolated from most adult tissues, including bone marrow, adipose, liver, amniotic fluid, lung, skeletal muscle and kidney. The term MSC is currently being used to represent both mesenchymal stem cells and multipotent mesenchymal stromal cells. Numerous reports on systemic administration of MSCs leading to functional improvements based on the paradigm of engraftment and differentiation have been published. However, it is not only difficult to demonstrate extensive engraftment of cells, but also no convincing clinical results have been generated from phase 3 trials as of yet and prolonged responses to therapy have been noted after identification of MSCs had discontinued. It is now clear that there is another mechanism by which MSCs exert their reparative benefits. Recently, MSCs have been shown to possess immunomodulatory properties. These include suppression of T cell proliferation, influencing dendritic cell maturation and function, suppression of B cell proliferation and terminal differentiation, and immune modulation of other immune cells such as NK cells and macrophages. In terms of the clinical applications of MSCs, they are being tested in four main areas: tissue regeneration for cartilage, bone, muscle, tendon and neuronal cells; as cell vehicles for gene therapy; enhancement of hematopoietic stem cell engraftment; and treatment of immune diseases such as graft-versus-host disease, rheumatoid arthritis, experimental autoimmune encephalomyelitis, sepsis, acute pancreatitis and multiple sclerosis. In this review, the mechanisms of immunomodulatory effects of MSCs and examples of animal and clinical uses of their immunomodulatory effects are described.

Outcomes of sinus surgery in ambulatory patients with immune dysfunction.

BACKGROUND: Previous outcomes studies of patients with chronic rhinosinusitis (CRS) have mostly excluded subjects with immunodeficiency or autoimmune disease. Although expert opinion suggests these patients are often refractory to therapy, outcomes after endoscopic sinus surgery (ESS) are not well delineated. We evaluated improvement in objective and quality of life (QoL) measures after ESS in adult patients treated in the ambulatory setting with immune dysfunction including immunodeficiency and autoimmune diseases. METHODS: Patients with CRS associated with immune dysfunction (n = 22) were evaluated and matched 1:1 with control subjects from a prospective cohort in a nested case-control design. Preoperative computed tomography (CT) and pre-/postoperative endoscopic findings were recorded. Disease-specific QoL instruments (the Rhinosinusitis Disability Index [RSDI] and Chronic Sinusitis Survey [CSS]) were administered pre- and postoperatively. RESULTS: Mean postoperative follow-up was similar for both cases (18.6 +/- 6.6 months) and controls (18.4 +/- 8.7 months). Preoperative CT and endoscopy scores (i.e., disease severity) were similar in both cases and controls. Postoperative endoscopy scores were significantly improved for both cases (p < 0.001) and controls (p = 0.012). Both groups had similar preoperative and postoperative scores on the CSS; however, control subjects reported significantly worse RSDI baseline scores. Immunodeficiency and autoimmune cases and CRS controls experienced significant improvement in QoL after surgery (p < or = 0.041). CONCLUSION: Immunodeficiency and autoimmune cases, in the ambulatory setting, present with similar severity of disease when compared with controls with CRS. We found similar improvements in both objective and QoL outcomes for case subjects and control subjects, suggesting that patients with immune dysfunction may experience similar benefit from ESS.

Perioperative considerations in diabetic patients.

Diabetes mellitus is an increasingly common disease that affects people of all ages, resulting in significant morbidity and mortality. Diabetic patients require more frequent hospitalization, have greater lengths of stay, and cost more to manage than non-diabetics. The major risk factors for diabetics undergoing surgery are the end-organ diseases associated with diabetes: cardiovascular disease, autonomic neuropathy and immune deficiency. Physicians should pay extra attention to preoperative and preprocedure evaluation and treatment of these diseases to ensure optimal perioperative management. Furthermore, these patients unexpectedly develop hemodynamic instability in response to vasopressor or vasodilator administration during anesthesia, this being of particular importance in patients with concurrent ischemic heart disease in whom it may have a direct effect on mortality. Recent studies have shown that tight glycemic control in diabetic patients undergoing major surgery has been shown to improve perioperative morbidity and mortality.

Hematopoietic stem cell transplantation in Iran: 1991 to 2008.

Since 1991, 2042 first hematopoietic stem cell transplants (HSCT) have been performed at the Hematology-Oncology and Stem Cell Transplantation Research Center at Tehran University of Medical Sciences. Acute myelogenous leukemia (548 patients), thalassemia major (335 patients) and acute lymphoblastic leukemia (275 patients) have been the most common transplanted disorders. There were 1418 cases that received allogeneic HSCT and 624 cases that have received autologous HSCT. The numbers of allogeneic and autologous HSCT have increased, but the allogeneic to autologous ratio has remained constant. The first peripheral blood hematopoietic stem cell transplantation was performed in 1996; since then, 1671 have been done. The donor types for 1418 allogeneic first HSCT were 1367 (96.4%) human leukocyte antigen (HLA) matched-identical siblings, 29 (2%) HLA-mismatched sibling/other relative, 13 (0.9%) syngeneic twins, 5 (0.4%) HLA-matched other relatives and 4 (0.3%) unrelated. The first cord blood hematopoietic stem cell transplantation was performed in 1998 and since then there have been 14 patients that have obtained cord blood transplantations. Recently, new methods have been used like donor lymphocyte infusion (DLI) and cellular therapy. There were 111 patients with cellular therapy for post-myocardial infarction, cirrhosis, thalassemia major, multiple sclerosis, head of femur necrosis and renal cell carcinoma.

Perioperative care of the immunocompromised patient.

Immunity refers to the body's capacity to resist invading organisms and toxins, thereby preventing tissue and organ damage. A patient whose immune system is impaired may be at higher risk for untoward perioperative events. Some populations most at risk for immunocompromise include infants, geriatric patients, people who have undergone organ transplantation, and people with cancer. Patients who are immunocompromised have an increased risk for hypothermia, which can affect postoperative wound healing processes and can increase the risk of wound infection. This article provides a basic overview of the immune system, a discussion of common disorders and diseases of the immune system, and a guide for perioperative nurses to use when they care for a patient who is immunocompromised.

Predictive factors for successful laparoscopic splenectomy in immune thrombocytopenic purpura: study of clinical and laboratory data.

BACKGROUND: Laparoscopic splenectomy (LS) offers better short-term results than open surgery for the treatment of immune thrombocytopenic purpura (ITP), but long-term follow-up is required to ensure its efficacy. The remission rate after splenectomy ranges from 49 to 86% and the factors that predict a successful response to surgical management have not been clearly defined. The goal of this study was to determine the preoperative factors that predict a successful outcome following LS. METHODS: From February 1993 to December 2003, LS was consecutively performed in a series of 119 nonselected patients diagnosed with ITP (34 men and 85 women; mean age, 41 years), and clinical results were prospectively recorded. Postoperative follow-up was based on clinical records, follow-up data provided by the referring hematologist, and a phone interview with the patient and/or relative. Univariate and multivariate analyses were performed for clinical preoperative variables to identify predictive factors of success following LS. RESULTS: Over a mean period of 33 months, 103 patients (84%) were available for follow-up with a remission rate of 89% (92 patients, 77 with complete remission with platelet count > 150,000). Eleven patients did not respond to surgery (platelet count < 50,000). Mortality during follow-up was 2.5% (two cases not related to hematological pathology and one case without response to splenectomy). Preoperative clinical variables evaluated to identify predictive factors of response to surgery were sex, age, treatment (corticoids alone or associated with Ig or chemotherapy), other immune pathology, duration of disease, and preoperative platelet count. In a subgroup of 52 patients, we also evaluated the type of autoantibodies and corticoid doses required to maintain a platelet count > 50,000. Multivariate analysis showed that none of the variables evaluated could be considered as predictive factors of response to LS due to the high standard error. CONCLUSION: Long-term clinical results show that LS is a safe and effective therapy for ITP. However, a higher number of nonresponders is needed to determine which variables predict response to LS for ITP.

Hematologic aspects of myeloablative therapy and bone marrow transplantation.

The transplantation of bone marrow cells or isolated hematopoietic stem cells from the bone marrow or peripheral blood is a widely utilized form of therapy for patients with incurable diseases of the hematopoietic and immune systems. Successful engraftment of the transplanted stem cells in an adequately prepared recipient normally leads to bone marrow reconstitution over a period of several weeks, accompanied by more gradual reconstitution of the immune system. Since the recipient is profoundly ill during the initial treatment period, laboratory data is critical for monitoring engraftment, detecting residual/recurrent disease, and identifying problems that may delay bone marrow reconstitution or lead to other medical complications. Accurate blood cell counts are imperative, and most bone marrow transplantation patients undergo periodic monitoring with bone marrow aspirates and biopsies with cytogenetic, molecular, and multiparametric flow cytometric studies. The potential complications of bone marrow transplantation include engraftment failure and delayed engraftment, infection, residual bone marrow disease, acute and chronic graft versus host disease, myelofibrosis, therapy-related acute leukemia, post-transplant lympho-proliferative disorders, and toxic myelopathy.

[Disorders of immunity in chest and abdominal injuries]. / Narusheniia immuniteta pri povrezhdeniiakh grudi i zhivota.

Under study were disturbances in the immune competent system in 245 patients with injuries of the chest and abdomen in dynamics of the early posttrauma period. Specific features of the disturbances were analyzed in the complicated and noncomplicated course of the trauma disease. The informative value and prognostic significance of certain indices are discussed as well as approaches to immune correction.