Iatrogenesis is more common in neonatal intensive care units (NICUs) because the infants are vulnerable and exposed to prolonged intensive care. Sixty percent of extremely low-birth-weight infants are exposed to iatrogenesis. The risk factors for iatrogenesis in NICUs include prematurity, mechanical or non-invasive ventilation, central lines, and prolonged length of stay. This led to the notion that “less is more.” In the delivery room delayed cord clamping is recommended for term and preterm infants, and suction for the airways in newborns with meconium-stained fluid is not performed anymore. As a symbol for a less aggressive attitude we use the term neonatal stabilization rather than resuscitation. Lower levels of oxygen saturations are accepted as normal during the first 10 minutes of life, and if respiratory assistance is needed, we no longer use 100% oxygen but 0.21–0.3 FiO2, depending on gestational age and the level of oxygen saturation. We try to avoid endotracheal ventilation by using non-invasive respiratory support and administering continuous positive airway pressure early on, starting in the delivery room. If surfactant is needed, non-invasive methods of surfactant administration are utilized. Use of central lines is shortened, and early feeding of human milk is the routine. Permissive hypercapnia is allowed, and continuous non-invasive monitoring not only of the O2 but also of CO2 is warranted. “Kangaroo care” and Newborn Individualized Developmental Care and Assessment Program (NIDCAP) together with a calm atmosphere with parental involvement are encouraged. Whether “less is more,” or not enough, is to be seen in future studies.
Objective: The growing availability of next-generation sequencing technologies has revolutionized medical genetics, facilitating discovery of causative genes in numerous Mendelian disorders. Nevertheless, there are still many undiagnosed cases. We report the experience of the Genetics Institute at Rambam Health Care Campus in rare disease diagnostics using whole-exome sequencing (WES).
Methods: Phenotypic characterization of patients was done in close collaboration with referring physi-cians. We utilized WES analysis for diagnosing families suspected for rare genetic disorders. Bioinformatic analysis was performed in-house using the Genoox analysis platform.
Results: Between the years 2014 and 2017, we studied 34 families. Neurological manifestations were the most common reason for referral (38%), and 55% of families were consanguineous. A definite diagnosis was reached in 21 cases (62%). Four cases (19%) were diagnosed with variants in novel genes. In addition, six families (18%) had strong candidate novel gene discoveries still under investigation. Therefore, the true diagnosis rate is probably even higher. Some of the diagnoses had a significant impact such as alerting the patient management and providing a tailored treatment.
Conclusions: An accurate molecular diagnosis can set the stage for improved patient care and provides an opportunity to study disease mechanisms, which may lead to development of tailored treatments. Data from our genetic research program demonstrate high diagnostic and novel disease-associated or causative gene discovery rates. This is likely related to the unique genetic architecture of the population in Northern Israel as well as to our strategy for case selection and the close collaboration between analysts, geneticists, and clinicians, all working in the same hospital.
Cancer patients have a pro-thrombotic state attributed to the ability of cancer cells to activate the coagula¬tion system and interact with hemostatic cells, thus tilting the balance between pro- and anticoagulants. Mechanisms underlying the coagulation system activation involve tumor cells, endothelial cells, platelets, and white blood cells. Anti-cancer therapies, including anti-angiogenic drugs, significantly increase the risk of thrombosis during treatment. Along with the role of coagulation proteins in the hemostatic system, these proteins also serve as growth factors to the tumor. Heparanase is a pro-angiogenic and pro-metastatic protein. Our previous studies have demonstrated that it enhances tissue factor (TF) activity and is present at high levels in tumor cells and patients’ blood. Strategies to attenuate heparanase effects by heparin mimetics or peptides interrupting the TF–heparanase interaction are good candidates to attenuate tumor growth and thrombotic manifestations.
Objectives: Research and theory suggests that socioeconomic status may affect diabetes control. We investigated the effect of socioeconomic status and ethnicity on glycated hemoglobin (HbA1c) in Arab and Jewish children with type 1 diabetes mellitus in northern Israel.
Methods: Data were collected from medical records of 80 Arab and 119 Jewish children attending a pediatric diabetes clinic in a tertiary health care center. Multivariate regression analysis was used to assess factors independently affecting HbA1c level.
Results: Mean age was 12.9±4.7 years. Arab families had more children compared to Jewish families (3.7±1.5 versus 2.9±1.2, respectively, P=0.0007). Academic education was significantly less common in Arab families (25% versus 66.2%, respectively, P=0.0001). Income of Jewish parents was significantly higher compared to that of Arab parents (7,868±2,018 versus 5,129±906 NIS/month, respectively, P=0.0001). Mean age at diagnosis of diabetes was 9.6±4.6 years and disease duration was 3.4±2.3 years in both groups. Half of Arab and Jewish children were treated with multiple insulin injections and half with insulin pumps. Mean number of self-glucose testing/day was higher in Jewish children than in Arab children (4.7±2.5 versus 4.0±1.5, respectively, P=0.033). Mean HbA1c was above recommendations, 9.5% (12.6 mmol/L) in Arab children and 8.7% (11.3 mmol/L) in Jewish children (P=0.004). In multivariate analysis, disease duration (P=0.010) and ethnicity (P=0.034 for Arabs versus Jews) were independently associated with HbA1c.
Conclusions: Both Arab and Jewish children failed to meet HbA1c goals, but this effect was significantly greater for Arabs. Ethnicity remained a predictor of failure even following adjustment for potential confounders.
Objective of the work: Pancreatic cancer (PC) is a deadly disease that is most commonly diagnosed at an incurable stage. Early diagnosis is the most important factor for improving prognosis. Evidence is beginning to accumulate that screening and surveillance may lead to the early detection of precursor lesions and/or pancreatic cancer in asymptomatic individuals. Proper screening methods and identification of such precursor lesions may enable effective pre-emptive interventions to prevent further fatalities. The primary objective of this project was to examine the feasibility of identifying precursor or early cancerous lesions in high-risk individuals by endoscopic ultrasound (EUS) screening to prevent the deaths from pancreatic cancer.
Research aim: Pancreatic cancer screening guidelines, based on consensus opinions, have been applied in various tertiary centers around the world; however, evidence for effectiveness is lacking. At Rambam Health Care Campus, we have established a cohort of high-risk individuals, and we report our local 10-year experience results of screening for pancreatic cancer.
Methods: Between 2008 and 2018, a cohort of 123 asymptomatic high-risk individuals came for annual/biannual EUS screening for pancreatic cancer. Retrospective and prospectively collected data were obtained, analyzed, and compared on the basis of several variables. These variables include age at beginning of screening, gender, smoking, obesity, diabetes, and presence of tumor markers, as well as the patients’ personal and family history of cancers. Findings on each EUS are described.
Results: Three patients out of 123 underwent potentially life-saving surgery as a result of this screening program. All of these three had only one first-degree relative (FDR) with pancreatic cancer at the time of their first screenings, but two eventually had a second FDR with PC. Findings from 296 EUS exams regarding smoking, obesity, and other risk factors are presented. Minor, possibly trivial, EUS findings are found to be common. Detection of precursor pancreatic lesions is feasible with EUS screenings.
Conclusions: Adherence was an important limiting factor in screening. Better stratification of patients according to specific risk factors, including thorough genetics and family history, may direct when and how to initiate screening. International collaborations, such as the International Cancer of Pancreas Screening (CAPS) Consortium, of which Rambam is a collaborating partner, are needed to collate evidence for impact of screening to prevent pancreatic cancer morbidity and mortality, and are essential to achieve proof of concept. Different countries with varying health-care systems and budgets can find variance of appropriateness of screening procedures.
Dear Friends and Colleagues,
Since its launch in 2010, Rambam Maimonides Medical Journal (RMMJ) has focused on its mission of expanding the knowledge base of medicine, science, humanity, and ethics throughout the world, flavored by the salt of the 850-year-old philosophy of Rabbi Moshe Ben Maimon—known by the Hebrew acronym “RAMBAM” or, more commonly, as Maimonides.
Introduction: Dyspnea is prominently observed in palliative care (PC). Dyspnea can be multifactorial, primarily caused by obstructive or restrictive lung diseases or secondarily induced by various comorbidities. Numerous interventions exist, with route of administration and efficacy requiring further discussion. Despite opioids being the first line of treatment, their adverse effects lead to reluctance on the side of patients to take them, creating limitations in patient management planning.
Objectives: This paper reviews and highlights the role of inhalers for dyspnea management in PC.
Methods: The CINAHL, CENTRAL, and OVID databases were searched for scholarly articles on the role of inhalers in dyspnea management from 1998 to the present. A grey literature Internet search was also performed via Google, the World Health Organization, and CareSearch. Twenty-five articles relevant to the subject at hand were located and summarized. The Cochrane Systematic Reviews of Health Promotion and Public Health Interventions Handbook was consulted for structuring.
Result: Isolated bronchodilators can be effective in dyspnea management. However, combination with opioids leads to a 52% reduction of dyspnea, demonstrating efficacy of their combined use. There is a role for conventional inhalers not only in patients afflicted with chronic obstructive pulmonary disease, but also in those where obstruction is reversible, and in cases of dyspnea not yet diagnosed.
Conclusion: Inhalers can be utilized as adjuvant therapy to opioids, to limit opioid use, augment responses to dyspnea, and/or minimize opioid side effects, especially in opioid-naïve patients. Correct administration can increase the efficacy of short-acting beta-agonists, long-acting beta-agonists, short- and long-acting anticholinergic agents, and inhaled corticosteroids, achieving reduction and alleviation of dyspnea.
All natural animals and plants are holobionts, consisting of the host and microbiome, which is composed of abundant and diverse microorganisms. Health and disease of holobionts depend as much on interactions between host and microbiome and within the microbiome, as on interactions between organs and body parts of the host. Recent evidence indicates that a significant fraction of the microbiome is transferred by a variety of mechanisms from parent to offspring for many generations. Genetic variation in holobionts can occur in the microbiome as well as in the host genome, and it occurs more rapidly and by more mechanisms in genomes of microbiomes than in host genomes (e.g. via acquisition of novel microbes and horizontal gene transfer of microbial genes into host chromosomes). Evidence discussed in this review supports the concept that holobionts with their hologenomes can be considered levels of selection in evolution. Though changes in the microbiome can lead to evolution of the holobiont, it can also lead to dysbiosis and diseases (e.g. obesity, diarrhea, inflammatory bowel disease, and autism). In practice, the possibility of manipulating microbiomes offers the potential to prevent and cure diseases.
Stents are widely use in endoscopic urological procedures. One of the most important indications is the treatment of urinary tract strictures. Allium™ Medical has introduced several types of stents for the treatment of different types of urinary tract strictures, based on anatomic location. All the stents are made of nitinol and coated with a co-polymer that reduces encrustations. These stents are self-expandable and have a large caliber and a high radial force. They have different shapes, designed especially for the treatment of each type of stricture. One of the most important features of Allium-manufactured stents is the ease of removal, due to their special unraveling feature. The company has introduced the Bulbar Urethral Stent (BUS) for treatment of bulbar urethral strictures; a rounded stent available in different lengths. Initial data on 64 patients with bulbar urethral stricture treated with the BUS showed a significant improvement in symptoms, with minimal complications and few adverse events. For treatment of prostate obstruction in patients unfit for surgery or unwilling to undergo a classical prostatic surgery, the Triangular Prostatic Stent (TPS) was introduced, which has a triangular shape that fits in the prostatic urethra. Its body has a high radial force attached to an anchor (which prevents migration) through a trans-sphincteric wire (which reduces incontinence rate). Initial data on 51 patients showed significant improvement in symptoms and in urinary peak flow rate, with a relatively small number of complications. The Round Posterior Stent (RPS) was designed for treatment of post radical prostatectomy bladder neck contracture. This short, round stent has an anchor, which is placed in the bladder neck. This stent being relatively new, the clinical data are still limited. Ureteral strictures can be treated with the Ureteral Stent (URS), which is round-shaped, available in different lengths, and has an anchor option (for very distal or very proximal strictures). We have previously published data on 107 URSs inserted in patients with ureteral stricture due to several etiologies, including patients who failed previous treatment. All patients were asymptomatic for a long period of follow-up after stent removal, with only one case of re-stenosis. In this paper, we review the urological “covered” stents produced by Allium Medical with the relevant clinical data available at the present time.
Objective: The objective of this study was to retrospectively review clinical data, management protocols, and clinical outcomes of patients with fibromatoses of head and neck region treated at our tertiary care center.
Methods: We retrospectively reviewed the medical records of 11 patients with confirmed histopathological diagnosis of fibromatosis registered in the Department of Head and Neck Surgery at Tata Memorial Centre, India, between 2009 and 2019. Various clinical and pathological features and treatment modalities were evaluated.
Results: Age at diagnosis ranged between 18 and 74 years, with a median age of 36 years. The female-to-male ratio was 5:6. Supraclavicular fossa (n=4) was the most common subsite of origin in the neck (n=8). The lateral (n=2) and posterior cervical regions (n=2) were other common neck subsites. Less commonly involved sites were the mandible (n=1), maxilla (n=1), and thyroid (n=1). A total of eight patients underwent surgery at other centers before being referred to us for further management. Out of a total 11 patients, nine patients had unresectable disease at presentation. Six of the patients with unresectable disease received a combination of weekly doses of vinblastine 6 mg/m2 and methotrexate 30 mg/m2 for a median duration of 6 months (range 6–18 months) followed by hormonal therapy with tamoxifen. Three patients received metronomic chemotherapy followed by hormonal therapy. One treatment-naive patient with fibromatosis of posterior cervical (suboccipital) region underwent R2 resection (excision of bulk of the tumor with preservation of critical structures) at our center along with adjuvant radiotherapy. One pregnant patient reported to us after undergoing surgery outside and defaulting radiotherapy. During median follow-up of 29 months (range 1–77 months), six patients had stable disease, and four patients had disease reduction. Disease progression was seen in one patient. The two-year progression-free survival (PFS) was 90% (95% CI 70%–100%).
Conclusion: Gross residual resection (R2) was the mainstay of surgical treatment in our series as obtaining clear surgical margins is seldom possible in these locally aggressive tumors. Radiotherapy, chemotherapy, and hormonal therapy are the other preferred and more conservative treatment modalities. The goal of surgery should be preserving function with minimal or no morbidity. As fibromatoses in the head and neck region are extremely rare, their treatment awaits the development of standard treatment protocols.
