Chronic hepatitis C virus (HCV) infection is a leading cause of liver disease worldwide and remains the most common indication for liver transplantation. The current standard of care leads to a sustained vir-al response of roughly 50% of treated patients at best. Furthermore, anti-viral therapy is expensive, pro-longed, and associated with serious side-effects. Evidence suggests that a poor response to treatment may be the result of a suppressed anti-viral immunity due to the presence of increased numbers and activity of CD4+CD25+Foxp3+ regulatory T cells (Treg cells). We and others have recently identified fi-brinogen-like protein 2 (FGL2) as a putative effector of Treg cells, which accounts for their suppressive function through binding to Fc gamma receptors (FcγR). In an experimental model of fulminant viral hepatitis, our laboratory showed that increased plasma levels of FGL2 pre- and post-viral infection were predictive of susceptibility and severity of disease. Moreover, treatment with antibody to FGL2 fully protected susceptible animals from the lethality of the virus, and adoptive transfer of wild-type Treg cells into resistant fgl2-deficient animals accelerated their mortality post-infection. In patients with HCV infection, plasma levels of FGL2 and expression of FGL2 in the liver correlated with the course and severity of the disease. Collectively, these studies suggest that FGL2 may be used as a biomarker to pre-dict disease progression in HCV patients and be a logical target for the development of novel therapeu-tic approaches for the treatment of patients with HCV infection.
Objective: We hypothesized that ultrasound (US)-guided technique of the supra- and infraclavicular and axillary approaches of brachial plexus block (BPB) will produce a high quality of surgical anesthesia for operations below the shoulder independently of the approach and body mass index (BMI). Intercosto-brachial and medial brachial cutaneous nerves will be blocked separately because they are not a part of the brachial plexus.
Methods: This is a prospective randomized observer-blinded study. The three approaches of the US-guided BPB without neurostimulation were compared for quality, performance time, and correlation between performance time and BMI. Intercostobrachial and medial brachial cutaneous nerve blocks were used in all patients.
Results: A total of 101 patients were randomized into three groups: SCL (supraclavicular), ICL (infra-clavicular), and AX (axillary). Seven patients were excluded due to various factors. All three groups were similar in demographic data, M:F proportion, preoperative diagnosis and type of surgery, anesthesiologists who performed the block, and surgical staff that performed the surgical intervention. The time between the end of the block performance and the start of the operation was also similar. The quality of the surgical anesthesia and discomfort during the operation were identical following comparison between groups. No direct positive correlation was observed between BMI and the block performance time. The time for the axillary block was slightly longer than the time for the supra- and infraclavicular approaches, but it had no practical clinical significance. Transient Horner syndrome was observed in three patients in the SCL group. No other adverse effects or complications were observed.
Conclusions: All three approaches can be used for US-guided BPB with similar quality of surgical anesthesia for operations of below the shoulder. A block of the intercostobrachial and medial brachial cutaneous nerves is recommended. Obesity is not a significant factor in relation to the time of US-guided BPB performance, or the quality of surgical anesthesia. (ClinicalTrials.gov number, NCT01442558.)
Objective: To compare the results of treating patients with common bile duct (CBD) stones by endoscopic sphincterotomy (ES), surgical exploration, or a combination of ES and surgical CBD exploration (the rendezvous technique).
Methods: A narrative review of the literature.
Summary of Data: Before 1990, 17 cohort studies indicated that ES cleared CBD stones in 92.0% of patients, with a mortality rate of 1.5%. Surgery removed CBD stones in 90.2% of patients, with a 2.1% mortality rate. A single randomized controlled trial in 1987 showed that ES removed CBD stones in 91% of 55 patients, with a 3.6% mortality rate and a 27% complication rate, whereas surgical CBD exploration removed CBD stones in 92%, with a 1.8% mortality rate and a 22% complication rate. Since 1991, 26 randomized controlled trials have shown that laparoscopic–ES rendezvous is as effective as ES alone and laparoscopic surgery alone but is associated with fewer complications, a reduced need for additional procedures, and a shorter hospital stay.
Conclusions: A laparoscopic–ES rendezvous appears to be the optimal approach to the treatment of CBD stones in younger and fit patients. The choice between ES alone and laparoscopic–ES rendezvous in older or high-risk patients remains uncertain.
Quantification of the T cell receptor excision circles (TRECs) has recently emerged as a useful non-invasive clinical and research tool to investigate thymic activity. It allows the identification of T cell production by the thymus. Quantification of TREC copies has recently been implemented as the preferred test to screen neonates with severe combined immunodeficiency (SCID) or significant lymphopenia. Neonatal genetic screening for SCID is highly important in countries with high rates of consanguinous marriages, such as Israel, and can be used for early diagnosis, enabling prompt therapeutic intervention that will save lives and improve the outcome of these patients. TREC measurement is also applicable in clinical settings where T cell immunity is involved, including any T cell immunodeficiencies, HIV infection, the aging process, autoimmune diseases, and immune reconstitution after bone marrow transplantation.
TAKE-HOME MESSAGES
• Severe combined immunodeficiency, a life-threatening condition, can be detected by neonatal screening.
• The earlier the detection and the quicker the implementation of appropriate treatment, the greater the likelihood for improved outcome, even cure, for the affected children.
• TRECs and KRECs quantification are useful screening tests for severe T and B cell immunodeficiency and can be used also to evaluate every medical condition involving T and B cell immunity.
Pain medicine in Israel and in the world has reached a crisis. The lack of available pain medicine services is resulting in the unsatisfactory treatment for chronic pain sufferers. The main causes of this crisis are: 1) the high prevalence of chronic pain, reaching levels of 17% in the adult population;2) the lack of appropriate training of primary care physicians in the field of chronic pain management; and 3) the paucity of consultation services in the field of chronic pain.
In this journal article, we propose a possible model for the solution of the problem, based upon levels of treatment according to the severity of the disease and upon training of primary and secondary care physicians in the treatment of pain. According to the model, the vast majority of treatment and management will take place in the community after appropriate training of primary care physicians. More complex cases will be referred to secondary care community-based pain clinics manned by physicians with further in-depth training. Only the most complex of patients, or those needing specialized treatment such as invasive analgesic therapy, will be referred to tertiary pain centers manned by specialists in pain medicine.
Implementation of this model will necessitate training of primary care physicians and the establishment of secondary care facilities and can, in our opinion, pose a pragmatic solution for the hundreds of thousands of patients suffering from chronic pain.
More than 11,000 articles lauding alternative medicine appear in the PubMed database, but there are only a few articles describing the complications of such care. Two patients suffering from complications of alternative medicine were treated in our hospital: one patient developed necrotizing fasciitis after acupuncture, and the second developed an epidural hematoma after chiropractic manipulation. These complications serve as a clarion call to the Israeli Health Ministry, as well as to health ministries around the world, to include complementary medicine under its inspection and legislative authority.
Squamous cell carcinoma of the larynx continues to be the commonest head and neck cancer in many Western countries. The larynx plays a key role for many essential functions, including breathing, voice production, airway protection, and swallowing. The goals of laryngeal cancer treatment are thus to provide best possible oncologic control, while optimizing functional outcomes.
In recent decades, the treatment paradigm for advanced laryngeal cancer has shifted from one of primary surgery (total laryngectomy) as gold standard, toward non-surgical organ-preserving treatment using radiotherapy or chemoradiotherapy. However, concerns have emerged regarding functional outcomes after chemoradiotherapy, as well as possible decreased overall survival in patients with laryngeal cancer.
The purpose of the present review is to review surgical and non-surgical options for treatment of advanced laryngeal cancer, as well as the evidence supporting each of these.
The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has markedly increased over the last three decades mostly due to human papillomavirus (HPV)-related infections. Cancers resulting from HPV infection bear a better prognosis than those that are smoking-related. Because HPV-positive patients are often younger, with lower rates of co-morbid illness and longer overall life expectancies, long-term sequelae of therapy have become an important issue. Treatment of oropharyngeal cancers has typically involved the use of radiation and chemotherapy to avoid the morbidity of open surgery which included mandibulotomy and composite resection. Transoral robotic surgery (TORS) is an emerging treatment option for this disease, avoiding the morbidity of open approaches while providing excellent oncologic and functional outcomes. With overall survival rate at 2 years exceeding 80%, and local failure rate of less than 3%, patients receiving TORS report relatively good health-related quality of life (QOL) scores. The aim of the current review is to provide a summary of the current literature with regard to the oncologic and functional outcomes following treatment of OPSCC with TORS.
Thrombotic microangiopathies (TMAs) comprise a group of distinct disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia, and microvascular thrombosis. For many years distinction between these TMAs, especially between thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), remained purely clinical and hard to make. Recent discoveries shed light on different pathogenesis of TTP and HUS. Ultra-large von Willebrand factor (UL-VWF) platelet thrombi, resulting from the deficiency of cleavage protease which is now known as ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), were found to cause TTP pathology, while Shiga toxins or abnormalities in regulation of the complement system causes microangiopathy and thrombosis in HUS. TMAs may appear in various conditions such as pregnancy, inflammation, malignancy, or exposure to drugs. These conditions might cause acquired TTP, HUS, or other TMAs, or might be a trigger in individuals with genetic predisposition to ADAMTS-13 or complement factor H deficiency. Differentiation between these TMAs is highly important for urgent initiation of appropriate therapy. Measurement of ADAMTS-13 activity and anti-ADAMTS-13 antibody levels may advance this differentiation resulting in accurate diagnosis. Additionally, assessment of ADAMTS-13 levels can be a tool for monitoring treatment efficacy and relapse risk, allowing consideration of therapy addition or change. In the past few years, great improvements in ADAMTS-13 assays have been made, and tests with increased sensitivity, specificity, reproducibility, and shorter turnaround time are now available. These new assays enable ADAMTS-13 measurement in routine clinical diagnostic laboratories, which may ultimately result in improvement of TMA management.
Pregnancy is a physiological hypercoagulable state, preparing the mother for the hemostatic challenge of delivery. However, this is associated with an increased risk of venous thrombosis and placenta-mediated complications, which present major challenges for mother and fetus. Although these conditions are heterogeneous in their pathophysiology, hereditary and acquired thrombophilia has been associated with recurrent pregnancy loss and gestational vascular complications, such as early-onset pre-eclampsia and placental abruption. Prevention of such placenta-mediated complications, which collectively complicate up to 15% of pregnancies, is a major issue for women’s health. Prospective interventional studies stratified by current knowledge of pathophysiological mechanisms related to placental and systemic hemostatic alterations will impact on the management of pregnancies at risk of these complications.
