Role of biological agents in immune-mediated inflammatory diseases

A new era in the treatment of immune-mediated inflammatory disorders has begun with the clinical availability of anticytokine therapy. Biological agents that are currently available include 3 agents that decrease the activity of tumor necrosis factor-alpha (infliximab, adalimumab, etanercept) and an interleukin-1 receptor antagonist (anakinra), with many more in development. Those extraordinarily effective medications are an important addition to our therapeutic armamentarium, and, although originally developed for rheumatoid arthritis and Crohn disease, have been found to be efficacious in the treatment of seronegative spondyloarthropathies (psoriatic arthritis, ankylosing spondylitis) and juvenile rheumatoid arthritis. Their role is currently being defined in other autoimmune disorders such as uveitis, sarcoidosis, interstitial lung disease, vasculitis, inflammatory myopathies, graft-versus-host disease, and Sj?gren syndrome.     

Small Bowel Perforation due to Ingested Foreign body

Small bowel perforation due to ingested foreign body is a rare but potentially life-threatening event. We present here 4 cases of small intestinal perforation caused by accidental ingestion of foreign bodies, from a total of 1,100 surgical procedures in one unit over a one-year period (September 2016 -August 2017). All 4 cases occurred in elderly patients who were using an artificial denture. The clinical appearance was that of acute abdomen, and in one case there had been formation of an enterocutaneous fistula a long time after the foreign body was swallowed. Typically, preoperative abdominal computed tomography (CT) showed the possible presence of a foreign body, which was confirmed intraoperatively.All 4 patients underwent surgery. Removal of the foreign body was performed, followed by primary intestinal closure or small bowel resection with a side-to-side anastomosis. Three of the 4 patients had an uneventful postoperative course, but one died on the 10th postoperative day, due to a severe postoperative pulmonary infection.Old age and artificial denture use appear to be strong risk factors, and the time and location of the perforation, and the presence of co-morbidities are prognostic factors for a successful surgical outcome. The choice of the type of surgery is individualized. A high level of clinical suspicion and meticulous investigation of the entire small intestine are required to ensure the correct diagnosis and early intervention for a successful outcome.     

<Emphasis Type="Italic">TNFRSF13B/TACI</Emphasis> Alterations in Greek Patients with Antibody Deficiencies

TNFRSF13B/TACI defects have recently been associated with common variable immunodeficiency (CVID) pathogenesis. Considering that TNFRSF13B/TACI is very polymorphic and the frequency of its alterations may be different in various ethnic groups, we analyzed their prevalence in 47 Greek patients with antibody deficiencies, including CVID (16 patients), IgAD (16 patients), selective IgG4D (11 patients), and transient hypogammaglobulinemia of infancy (4 patients). A rather high frequency of TNFRSF13B/TACI defects was identified in patients with selective IgG4D (18.18%). Moreover, a patient with CVID was heterozygous in the common C104R mutation (6.25%). Both his children and a further healthy individual carried the same mutation, albeit without recurrent infections and/or hypogammaglobulinemia. The common polymorphisms V220A and P251L were identified in all disease subgroups, in an almost similar frequency with that observed in 259 healthy controls. Our data provide further evidence that TNFRSF13B/TACI alterations are not causative of CVID. Possibly, they predispose to humoral deficiencies and/or contribute to their phenotype when combined with other immune gene alterations.     

Hypochromic erythrocytes (%): a reliable marker for recognizing iron-restricted erythropoiesis and predicting response to erythropoietin in anemic patients with myeloma and lymphoma

The aim of the study was to evaluate the role of hypochromic erythrocytes (HYPO%) compared to “traditional” and novel markers of iron status and erythropoiesis in recognizing iron-restricted erythropoiesis (IRE) and predicting response to erythropoietin (rHuEPO) in anemic patients with myeloma and lymphoma. Forty-one newly diagnosed patients who received epoetin-beta at a subcutaneous weekly dose of 30,000 IU for 6 weeks were studied. Response to rHuEPO was observed in 27 patients (65.8%). Twelve non-responders received, additionally, 200 mg of IV iron sucrose, weekly, for 4 weeks. Evaluation of markers was performed at baseline and on weeks 1, 2 and 6 for all patients and also on weeks 7–10 for non-responders to rHuEPO. Baseline HYPO%, at a cut-off value of <5%, and an increment in reticulocyte absolute number (RETICS-AB) ≥ 50,000/μl and reticulocyte hematocrit (RETICS-Hct) ≥ 50%, between baseline and week 2, were independent predictive factors for response to rHuEPO. We found that these markers had superior predictive value for response to rHuEPO than four widely used predictive models. Furthermore, a baseline HYPO% count of above 5% proved superior over serum ferritin < 100 ng/ml and transferrin saturation < 20% in recognizing IRE. In conclusion, baseline HYPO% either alone or in combination with RETICS-AB or RETICS-Hct after 2 weeks of rHuEPO treatment could be reliably used in predicting response to rHuEPO. Additionally, HYPO% has proved a reliable marker for recognizing IRE before rHuEPO treatment and, thus, could be used for identifying patients who will benefit from IV iron supplementation.     

Adult-onset Still's disease: can recent advances in our understanding of its pathogenesis lead to targeted therapy?

Adult-onset Still's disease is a rare systemic inflammatory disease of unknown etiology, characterized by daily high, spiking fevers, evanescent rash, and arthritis. There is no single diagnostic test for adult-onset Still's disease; rather, the diagnosis is based on clinical criteria and necessitates the exclusion of infectious, neoplastic, and other 'autoimmune' diseases. Proinflammatory cytokines such as interleukin (IL)-1, IL-6, and IL-18, interferon-gamma, tumor necrosis factor, and macrophage colony-stimulating factor are elevated in patients with adult-onset Still's disease and are thought to have a major role in the pathogenesis of the disease. Treatment consists of nonsteroidal anti-inflammatory drugs, corticosteroids, immunosuppressants (methotrexate, gold, azathioprine, leflunomide, cyclosporin, and cyclophosphamide), intravenous immunoglobulin, and cytokine (tumor necrosis factor, IL-1 and IL-6) inhibitors. Recent advances in basic immunology have enhanced our ability to hinder the pathogenic mechanisms associated with adult-onset Still's disease and have led to a paradigm shift where targeted treatments have an increasingly important role.     

Acute Respiratory Distress due to Thymoma in a Patient Treated with TK Inhibitor: A Case Report and Review of the Current Treatment Options

Thymic malignancies are rare intrathoracic tumors that may be aggressive and difficult to treat in advanced stage. Surgery is the cornerstone of the management of thymomas: it is significant for the definite histopathological diagnosis and staging, and in most cases, it constitutes the first step of the treatment strategy. For patients with primary unresectable thymomas, the multimodal treatment schedule nowadays includes neoadjuvant chemotherapy, extensive surgery, adjuvant radiotherapy, and in some cases, adjuvant chemotherapy. A patient with a history of stage III COPD and an undiagnosed thoracic mass was admitted to the intensive care unit with acute respiratory distress. A radiologic evaluation by CT scan revealed a mass of 13 cm in diameter at the mediastinum. Fine needle aspiration was performed and revealed a thymoma. Due to poor performance status, the patient was not able to undergo surgery. He refused to be treated with neither chemotherapy nor radiotherapy, but due to EGFR overexpression, treatment with TK inhibitor was suggested. Fine needle aspiration biopsy is commonly used to identify metastasis to the mediastinum. However, it is less often employed as a primary diagnostic tool for tumors, particularly thymic neoplasms. The use of targeted therapies for the treatment of thymic malignancies has been described in the literature. Over the past years, significant efforts have been made to dissect the molecular pathways involved in the carcinogenesis of these tumors. Insights have been obtained following anecdotal clinical responses to targeted therapies, and large-scale genomic analyses have been conducted.     

Laparoscopic bilateral inguinal hernia repair: Should it be the preferred technique?

Inguinal hernias are amongst the most common conditions requiring general surgical intervention. For decades, the preferred approach was the open repair. As laparoscopy became more popular and available and more surgeons became familiarized with this modality, laparoscopic inguinal hernia repair became an alternative. The aim of this study is to assess the effectiveness of laparoscopic inguinal repair, with a focus on bilateral inguinal hernias. Initial reports have shown promising clinical outcomes compared to those of conventional repair of bilateral hernias. However, there are only a few studies concerning laparoscopic repair of bilateral hernias. It is yet to be proven that laparoscopy is the “gold standard” in the treatment of bilateral inguinal hernias. So far, the choice of an inguinal hernia repair technique has been up to each surgeon, depending on their expertise and available resources after taking into consideration each patient’s needs.     

The modified Clavien classification system: a standardized platform for reporting complications in transurethral resection of the prostate

Purpose

The aim of the study was to evaluate the applicability of the modified Clavien classification system (CCS) in grading perioperative complications of transurethral resection of the prostate (TURP).

Methods

All patients with benign prostatic hyperplasia submitted to monopolar TURP from January 2006 to February 2008 at a non-academic center were evaluated for complications occurring up to the end of the first postoperative month. All complications were classified according to the modified CCS independently by two urologists, and the final decision was based on consensus. If multiple complications per patient occurred, categorization was done in more than one grade. Results were presented as complication rates per grade.

Results

Forty-four complications were recorded in 31 out of 198 patients (overall perioperative morbidity rate: 15.7%), and their grading was generally easy, non-time-consuming and straightforward. Most of them were classified as grade I (59.1%) and II (29.5%). Higher grade complications were scarce (grade III: 2.3% and grade IV: 6.8%, respectively) There was one death (grade V: 2.3%) due to acute myocardial infarction (overall mortality rate: 0.5%). Negative outcomes such as mild dysuria during this early postoperative period or retrograde ejaculation were considered sequelae and were not recorded. Nobody was complicated with severe dysuria. There was one re-operation due to residual adenoma (0.5%).

Conclusions

The modified CCS represents a straightforward and easily applicable tool that may help urologists to classify the complications of TURP in a more objective and detailed way. It may serve as a standardized platform of communication among clinicians allowing for sound comparisons.