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.
Alfred Nobel was one of the most successful chemists, inventors, entrepreneurs, and businessmen of the late nineteenth century. In a decision later in life, he rewrote his will to leave virtually all his fortune to establish prizes for persons of any nationality who made the most compelling achievement for the benefit of mankind in the fields of chemistry, physics, physiology or medicine, literature, and peace among nations. The prizes were first awarded in 1901, five years after his death. In considering his choice of prizes, it may be pertinent that he used the principles of chemistry and physics in his inventions and he had a lifelong devotion to science, he suffered and died from severe coronary and cerebral atherosclerosis, and he was a bibliophile, an author, and mingled with the literati of Paris. His interest in harmony among nations may have derived from the effects of the applications of his inventions in warfare (“merchant of death”) and his friendship with a leader in the movement to bring peace to nations of Europe. After some controversy, including Nobel’s citizenship, the mechanisms to choose the laureates and make four of the awards were developed by a foundation established in Stockholm; the choice of the laureate for promoting harmony among nations was assigned to the Norwegian Storting, another controversy. The Nobel Prizes after 115 years remain the most prestigious of awards. This review describes the man, his foundation, and the prizes with a special commentary on the Nobel Prize in Physiology or Medicine.
There is universal agreement that the Nobel Prizes, given to individuals who have made an extraordinarily notable contribution to humankind in the fields of chemistry, physics, physiology or medicine, literature, and peace, are the most prestigious prizes offered for human achievement. This commentary gives an overview of the basis for Alfred Nobel writing his third will that established the five prizes and includes a discussion of why those five fields were chosen. The commentary includes factors that influenced his choices and contains examples of controversial selections or omissions, especially in the earlier years. A few were errors of omission (e.g. Tolstoy, Tesla, Edison, Best, Gandhi, Franklin), some errors of commission (e.g. Fibiger, Moniz); but, given the complexity of the task, the error rate is small. In some cases, the conclusion that an error had been made is debatable. Such decisions are difficult. Arne Tiselius, a Nobel laureate in chemistry and President of the Nobel Foundation said that one cannot in practice apply the principle that the Nobel Prize should be given to the person who is best; it is impossible to define who is best. Hence, there is only one alternative: to try to find a particularly worthy candidate. This paper includes a brief review of the integration of the Sveriges Riksbank Prize in Economic Sciences in Memory of Alfred Nobel, established in 1968, and added to the original five Nobel Prizes; the prize was first awarded in 1969. A short discussion on the absence of a Nobel Prize in mathematics is provided. Adaptations to the development of “big” science, especially in physics, may require the Nobel Foundation to extend its limit of no more than three awardees for the prize in physics and, perhaps, other scientific disciplines.
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.
The world, as a global village, is currently taking part in a real-time public health, medical, socio-cultural, and economic experiment on how best to combat the COVID-19 pandemic. Extraordinary times demand extraordinary measures. Depending on the time from the outbreak, strategies have ranged from minimal intervention to mitigation by quarantine for high-risk groups (elderly with chronic illnesses) to containment and lockdown. Adherence to such restrictions have depended on the individual and national psyche and culture. One can understand and forgive governments for being over-cautious, but not for being ill-prepared. It seems that Singapore after SARS (2003) and South Korea after MERS (2015) learnt from their experiences and have fared relatively well with minimal disruption to daily routines. Coping with the challenge of COVID-19 is an urgent global task. We use the Sociotype ecological framework to analyze different coping responses at three levels: Context (government and leadership, social context, health services, and media); Relationships; and the Individual. We describe the many negative outcomes (e.g. mortality [obviously], unemployment, economic damage, food insecurity, threat to democracy, claustrophobia) and the positive ones (e.g. new, remote teaching, working, and medical routines; social bonding and solidarity; redefining existential values and priorities) of this surreal situation, which is still evolving. We highlight the importance of humor in stress reduction. Regular and reliable communication to the public has to be improved, acknowledging incomplete data, and learning to deal with fake news, misinformation, and conspiracy theories. Excess mortality is the preferred statistic to follow and compare outcomes. When the health risks are over, the economic recovery responses will vary according to the financial state of countries. If world order is to be reshaped, then a massive economic aid plan should be launched by the rich countries—akin to the Marshall plan after the Second World War. It should be led preferably by the USA and China. The results of the tradeoffs between health and economic lockdowns will only become apparent in the months to come. The experiences and lessons learned from this emergency should be used as a rehearsal for the next epi-/pandemic, which will surely take place in the foreseeable future.
Despite its status as a world leader in treatment innovation and medical education, a quality chasm exists in American health care. Care fragmentation and poor coordination contribute to expensive care with highly variable quality in the United States. The rising costs of health care since 1990 have had a huge impact on individuals, families, businesses, the federal and state governments, and the national budget deficit. The passage of the Affordable Care Act represents a large shift in how health care is financed and delivered in the United States. The objective of this review is to describe some of the economic and social forces driving health care reform, provide an overview of the Patient Protection and Affordable Care Act (ACA), and review model cardiovascular quality improvement programs underway in the state of Michigan. As health care reorganization occurs at the federal level, local and regional efforts can serve as models to accelerate improvement toward achieving better population health and better care at lower cost. Model programs in Michigan have achieved this goal in cardiovascular care through the systematic application of evidence-based care, the utilization of regional quality improvement collaboratives, community-based childhood wellness promotion, and medical device-based competitive bidding strategies. These efforts are examples of the direction cardiovascular care delivery will need to move in this era of the Affordable Care Act.
Combat trauma may affect servicemen from indigenous, traditional communities in ways that warrant special attention. The Bedouins, who enlist in the Israel Defense Forces (IDF) voluntarily, represent a unique, closed, collectivist cultural minority, potentially in a predicament in light of ongoing sociopolitical events. This paper summarizes findings and lessons learned from a community study of Bedouin IDF servicemen and their families residing in Israel’s Western Galilee. This is the only research endeavor to have addressed trauma exposure and posttraumatic reactions in this community. The sampling strategies and interview schedule were designed in consideration of participation barriers typical of hard-to-reach populations. Data collection followed an extended phase of liaising with key informants and building trust. Study limitations are discussed in terms of the challenges presented by this type of research. Interviews conducted with 317 men, 129 wives, and 67 mothers revealed high levels of trauma exposure and posttraumatic stress disorder (PTSD) in the men, and related distress in wives and mothers, but not in the children. The role of aggression in mediating the impact of PTSD and concepts such as shame, the loss of personal resources, and beliefs about retribution are highlighted as key issues for a culturally relevant understanding of traumatized indigenous communities.
CD4+CD25+Foxp3+ regulatory T cells (Treg) are critical to the maintenance of immune tolerance. Treg are known to utilize a number of molecular pathways to control immune responses and maintain immune homeostasis. Fibrinogen-like protein 2 (FGL2) has been identified by a number of investigators as an important immunosuppressive effector of Treg, which exerts its immunoregulatory activity by binding to inhibitory FcγRIIB receptors expressed on antigen-presenting cells including dendritic cells, endothelial cells, and B cells. More recently, it has been suggested that FGL2 accounts for the immunosuppressive activity of a highly suppressive subset of Treg that express T cell immunoreceptor with Ig and ITIM domains (TIGIT). Here we discuss the important role of Treg and FGL2 in preventing alloimmune and autoimmune disease. The FGL2–FcγRIIB pathway is also known to be utilized by viruses and tumor cells to evade immune surveillance. Moving forward, therapies based on modulation of the FGL2–FcγRIIB pathway hold promise for the treatment of a wide variety of conditions ranging from autoimmunity to cancer.
Introduction: Completion thyroidectomy is defined as the surgical removal of the remnant thyroid tissue following procedures of less than total or near-total thyroidectomy. Whether thyroid reoperations are associated with an increased complication risk is controversial.
Objective: A retrospective analysis was done of patients undergoing completion thyroidectomy for cancer of the thyroid who had undergone surgery elsewhere for solitary thyroid nodule. The incidence of surgical complications in these patients after reoperation was investigated in this study.
Material and Methods: The study included a total of 53 patients who had undergone thyroid lobectomy for a solitary nodule as initial surgery elsewhere and were referred to our institute for completion thyroidectomy when the histopathology revealed malignancy.
Results: There were 53 patients, 43 females and 10 males. Their mean age was 34.7±12.12 years (range 19–65 years). After initial surgery, the histopathology revealed papillary carcinoma in 46 patients (86.8%), follicular carcinoma in 7 (13.2%). Fourteen out of 53 patients had recurrent laryngeal nerve palsy after initial surgery (26.4%). None of the patients had clinical hypocalcemia after the first surgery. One or more parathyroid glands were identified and preserved in 52 patients (98.1%) in the process of completion thyroidectomy. No patient had additional recurrent nerve injury at the second surgery. The mean serum calcium value preoperatively was 8.96±0.39 mg/dL, and six months after surgery serum calcium was 8.74±0.56 mg/dL. Mean follow-up was 18 months. Transient hypoparathyroidism occurred in 24.5% patients. Five patients were lost to follow-up. Permanent and symptomatic hyperparathyroidism occurred in eight patients (16.67%).
Conclusions: Completion thyroidectomy is a safe and appropriate option in the management of well-differentiated thyroid cancer. It removes disease on the ipsilateral and contralateral side of the thyroid and carries a low risk of recurrent laryngeal nerve damage, but a higher risk of permanent hypoparathyroidism.
Background: It has been reported that a natural cycle (NC) is similar to or even better than hormone replacement therapy (HRT) in patients with regular cycles who undergo frozen embryo transfer (FET). Hundreds of FETs are managed yearly in our clinic. Scheduling these cycles is critical in a busy unit like ours. This is why we have to prove if a NC really shows a better outcome than other endometrium preparation protocols.
Methods: Hence we carried out a prospective study between June 2011 and June 2012, which included 530 patients (570 FET cycles) randomly allocated to two study groups: Group 1 (n=280 cycles), artificial cycle (HRT); or group 2 (n=290 cycles), natural cycle. Natural cycles were later divided into two groups: 169 patients scheduled with human chorionic gonadotropin (hCG) and 121 with endogenous luteinizing hormone (LH) surge. The inclusion criteria were: age <39 years, regular menstrual cycles (26–35 days), and previous IVF cycle with embryo cryopreservation. The exclusion criteria were polycystic ovarian syndrome and endometriosis stage III/IV.
Results: No statistical differences were found in the baseline characteristics among groups, nor between implantation or ongoing pregnancy rates (30.8% HRT group; 32.7% hCG group; 34.5% LH surge group). However, a higher miscarriage rate was observed in the HRT group when compared to hCG or LH surge (21.2 versus 12.9 versus 11.1%, P<0.01). Live birth rates were similar among groups, as were perinatal outcomes, for rates of natural delivery and weight and length of newborns.
Conclusions: We conclude that scheduling FET with HRT at weekends and avoiding work overload at weekends prove efficient and safe in cycle outcome terms. Another reason for the convenience of an HRT protocol is having fewer visits to the clinic compared to natural cycle protocols.
