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  • Third-trimester Reference Ranges for Cerebroplacental Ratio, Middle Cerebral Artery, and Umbilical Artery Pulsatility Index in Normal-growth Singleton Fetuses in the Israeli Population

    Background: The ratio between the fetal umbilical artery pulsatility index (UA-PI) and the middle cerebral artery pulsatility index (MCA-PI) is termed the cerebroplacental ratio (CPR). The CPR represents fetal blood flow redistribution at the early stages of placental insufficiency; moreover, it has predictive value for adverse intrapartum and neonatal outcomes. However, internationally accepted reference ranges for CPR are lacking. Objective: This study sought to establish UA-PI, MCA-PI, and CPR reference ranges in low-risk, normal-growth singleton fetuses during the third trimester of pregnancy. Methods: A retrospective cohort cross-sectional study was performed in the obstetrics ultrasound unit of a university hospital in Israel. We reviewed all fetal and maternal electronic records of pregnant women referred for ultrasound assessment during the third trimester between January 2014 and January 2019. We included only singleton pregnancies with normal anatomy scans and a normal third-trimester estimated fetal weight. The UA-PI, MCA-PI, and CPR reference ranges were reconstructed for each of the vessels for each gestational age between 29 and 41 weeks. Results: A total of 560 pregnancies met the inclusion criteria. Satisfactory waveforms and measurements were obtained in all cases. At least 18 women enrolled at each gestational week. The MCA-PI and CPR val-ues showed a similar parabolic curve during the third trimester of pregnancy, with a peak value at 32 and 33 gestational weeks, respectively. The UA-PI showed a linear and gradual decrease over the gestational age. Conclusions: In this study we established UA-PI, MCA-PI, and CPR reference ranges in low-risk, normal-growth singleton fetuses during the third trimester based on the Israeli population.
  • A Tale of Two Nineteenth-century Dutch Jewish Hospitals—One a Success, The Other a Failure

    The development of the modern hospital is usually dated to the nineteenth century. During this time, many municipal and sectarian hospitals were established and developed, and Jewish hospitals were no exception. Such developments also occurred in the Netherlands. This essay describes the different histories of the Jewish hospitals in Rotterdam and The Hague during the nineteenth century. The Rotterdam institution lasted for more than 130 years (until it was closed by the Nazis during the Second World War), whereas the one in The Hague existed for only 31 years. This study will suggest a number of possible explanations for the relatively long and successful history of the Jewish hospital in Rotterdam and the contrastingly brief duration of the Jewish hospital in The Hague.
  • Johannes Juda Groen (1903–1990): A Forgotten Visionary in the History of Medical Education

    Beyond the increase in medical knowledge and biotechnology during the last decades, doctors have adopted professional norms that would have been considered heretical only two generations ago. The changes transpired between the 1970s and 1990s, and generated controversies between those who upheld the traditional values of patient care, and those who welcomed the new professional norms. Professor Dr Johannes Juda Groen (1903–1990) predicted and promoted some of these changes. As early as the 1940s through the 1960s, he recognized the need to teach interviewing skills and advocated an orientation to patients, rather than to diseases; he supported decision-making based on evidence, rather than on personal experience and pathophysiologic rationale; and he demonstrated that psychosocial determinants predict, rather than only correlate with, disease. These views led to confrontations with the medical establishments in the Netherlands and in Israel. Still, many of his colleagues recognized the value of his contributions. The author, for one, admires Groen’s commitment in challenging the prevailing clinical wisdom after the end of World War 2, and his courage in opposing the views of his colleagues.
  • Transversus Abdominis Plane Versus Ilioinguinal and Iliohypogastric Nerve Blocks for Analgesia Following Open Inguinal Herniorrhaphy

    Objectives: We hypothesized that preoperative (pre-op) ultrasound (US)-guided posterior transversus abdominis plane block (TAP) and US-guided ilioinguinal and iliohypogastric nerve block (ILI+IHG) will produce a comparable analgesia after Lichtenstein patch tension-free method of open inguinal hernia repair in adult men. The genital branch of the genitofemoral nerve will be blocked separately. Methods: This is a prospective, randomized, controlled, and observer-blinded clinical study. A total of 166 adult men were randomly assigned to one of three groups: a pre-op TAP group, a pre-op ILI+IHG group, and a control group. An intraoperative block of the genital branch of the genitofemoral nerve was performed in all patients in all three groups, followed by postoperative patient-controlled intravenous analgesia with morphine. The pain intensity and morphine consumption immediately after surgery and during the 24 hours after surgery were compared between the groups. Results: A total of 149 patients completed the study protocol. The intensity of pain immediately after surgery and morphine consumption were similar in the two “block” groups; however, they were significantly decreased compared with the control group. During the 24 hours after surgery, morphine consumption in the ILI+IHG group decreased compared with the TAP group, as well as in each “block” group versus the control group. Twenty-four hours after surgery, all evaluated parameters were similar. Conclusion: Ultrasound-guided ILI+IHG provided better pain control than US-guided posterior TAP following the Lichtenstein patch tension-free method of open inguinal hernia repair in men during 24 hours after surgery. (ClinicalTrials.gov number: NCT01429480.)
  • ACPAs Are Much More Than Diagnostic Autoantibodies

    Anti-citrullinated protein autoantibodies (ACPAs) are the major autoantibodies in rheumatoid arthritis (RA). Anti-citrullinated protein autoantibodies are directed against different citrullinated antigens, including filaggrin, fibrinogen, vimentin, and collagen. Presence of ACPA is associated with joint damage and extra-articular manifestations, suggesting that ACPAs are most likely pathogenic autoantibodies in RA. In vitro, ACPAs induce macrophage tumor necrosis factor alpha (TNF-α) production, osteoclastogenesis, and complement activation. These autoantibodies also induce the formation of neutrophil extracellular traps (NETs). Additionally, ACPAs induce pathogenic cytokines expression and oxidative stress in immune cells derived from RA patients. The aim of this review is to show the pathogenic roles of these autoantibodies in RA.
  • Femoral versus Multiple Nerve Blocks for Analgesia after Total Knee Arthroplasty

    Background: The PROSPECT (Procedure-Specific Postoperative Pain Management) Group recommended a single injection femoral nerve block in 2008 as a guideline for analgesia after total knee arthroplasty. Other authors have recommended the addition of sciatic and obturator nerve blocks. The lateral femoral cutaneous nerve is also involved in pain syndrome following total knee arthroplasty. We hypothesized that preoperative blocking of all four nerves would offer superior analgesia to femoral nerve block alone. Methods: This is a prospective, randomized, controlled, and observer-blinded clinical study. A total of 107 patients were randomly assigned to one of three groups: a femoral nerve block group, a multiple nerve block group, and a control group. All patients were treated postoperatively using patient-controlled intravenous analgesia with morphine. Pain intensity at rest, during flexion and extension, and morphine consumption were compared between groups over three days. Results: A total of 90 patients completed the study protocol. Patients who received multiple nerve blocks experienced superior analgesia and had reduced morphine consumption during the postoperative period compared to the other two groups. Pain intensity during flexion was significantly lower in the “blocks” groups versus the control group. Morphine consumption was significantly higher in the control group. Conclusions: Pain relief after total knee arthroplasty immediately after surgery and on the first postoperative day was significantly superior in patients who received multiple blocks preoperatively, with morphine consumption significantly lower during this period. A preoperative femoral nerve block alone produced partial and insufficient analgesia immediately after surgery and on the first postoperative day. (Clinical trial registration number (NIH): NCT01303120)
  • Giant Cell Arteritis and Polymyalgia Rheumatica: 2016 Update

    Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are both more common among people of North European decent than among Mediterranean people. Women are 2–3 times more commonly affected. Giant cell arteritis and PMR are extremely rare before age 50 years. Polymyalgia rheumatica may be “isolated” or associated with GCA. There is increased expression of inflammatory cytokines in temporal arteries of PMR patients, without overt histological evidence of arteritis. One-third of “isolated” PMR patients have vascular uptake in positron emission tomography (PET) scans, suggesting clinically unrecognized, “hidden” GCA. Typical manifestations of GCA are headache, tenderness over temporal arteries, jaw claudication, PMR, acute vision loss, and low-grade fever. Bilateral aching of the shoulders with morning stiffness is typical for PMR. In both conditions sedimentation rate and C-reactive protein are elevated, and anemia and thrombocytosis may occur. Color duplex ultrasonography of the temporal arteries may aid in GCA diagnosis. Temporal artery biopsy showing vasculitis, often with giant cells, confirms GCA diagnosis. In cases with negative biopsy one must rely on the clinical presentation and laboratory abnormalities. The diagnosis of PMR is made primarily on clinical grounds. Other conditions that may mimic GCA or PMR must be excluded. Glucocorticoids are the treatment of choice for both conditions. Prompt treatment is crucial in GCA, to prevent irreversible complications of acute vision loss and stroke. Addition of low-dose aspirin may further prevent these complications. The average duration of treatment is 2–3 years, but some patients require a prolonged course of treatment, and some may develop disease-related or treatment-related complications. No steroid-sparing agent has been proven to be widely effective thus far, but some promising therapeutic agents are currently being studied.
  • Ehlers–Danlos Syndrome—Hypermobility Type: A Much Neglected Multisystemic Disorder

    Ehlers–Danlos syndrome (EDS)—hypermobility type (HT) is considered to be the most common subtype of EDS and the least severe one; EDS-HT is considered to be identical to the joint hypermobility syndrome and manifests with musculoskeletal complaints, joint instability, and soft tissue overuse injury. Musculoskeletal complaints manifest with joint pain of non-inflammatory origin and/or spinal pain. Joint instability leads to dislocation or subluxation and involves peripheral joints as well as central joints, including the temporomandibular joints, sacroiliac joints, and hip joints. Soft tissue overuse injury may lead to tendonitis and bursitis without joint inflammation in most cases. Ehlers–Danlos syndrome-HT carries a high potential for disability due to recurrent dislocations and subluxations and chronic pain. Throughout the years, extra-articular manifestations have been described, including cardiovascular, autonomic nervous system, gastrointestinal, hematologic, ocular, gynecologic, neurologic, and psychiatric manifestations, emphasizing the multisystemic nature of EDS-HT. Unfortunately, EDS-HT is under-recognized and inadequately managed, leading to neglect of these patients, which may lead to severe disability that almost certainly could have been avoided. In this review article we will describe the known manifestations of the extra-articular systems.
  • Atypical Femur Fractures in Patients Treated with Bisphosphonates: Identification, Management, and Prevention

    Osteoporosis is a common condition with significant health care costs. First-line therapy is with bisphosphonates, which have proven anti-fracture efficacy. Around 10 years after the introduction of bisphosphonates reports began to be published of atypical femoral fractures (AFFs) that may be associated with this therapy. These fractures are associated with significant morbidity although lower mortality than the more common osteoporotic neck-of-femur fractures. A case definition has been described to allow identification of this class of fracture. Further work has established a high relative risk of AFFs in patients treated with bisphosphonates, but a low absolute risk in comparison to that of osteoporotic fractures. Proposed pathological mechanisms include low bone turnover states leading to stress/insufficiency fractures. Clinicians should be aware of the risk of AFFs and in particular the high rate of prodromal thigh/groin pain that warrants investigation in a patient receiving a bisphosphonate. If an incomplete fracture is diagnosed then bisphosphonate therapy needs to be stopped and prophylactic surgery may be considered. Due to these rare side effects patients on bisphosphonates require regular review, and this is particularly advised after 5 years of oral or 3 years of intravenous therapy.
  • Comorbidities in Patients with Psoriatic Arthritis

    Epidemiological studies have shown that patients with psoriatic arthritis (PsA) are often affected by numerous comorbidities that carry significant morbidity and mortality. Reported comorbidities include diabetes mellitus, obesity, metabolic syndrome, cardiovascular diseases, osteoporosis, inflammatory bowel disease, autoimmune eye disease, non-alcoholic fatty liver disease, depression, and fibromyalgia. All health care providers for patients with PsA should recognize and monitor those comorbidities, as well as understand their effect on patient management to ensure an optimal clinical outcome.