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  • Adaptive Hybrid Surgery: Paradigm Shift for Patient Centered Neurosurgery

    The surgical management of cerebral and skull base lesions has evolved greatly in the last few decades. Still, a complete resection of lesions abutting critical neurovascular structures carries significant morbidity. Stereotactic radiosurgery (SRS) has emerged as an increasingly accepted treatment option. Minimally invasive, SRS results in excellent tumor control and low complication rates in patients with moderate-size tumors. The management of large cerebral and skull base tumors remains a formidable challenge. In such large tumors, radical surgical extirpation offers a significantly higher risk of neurological deficit, and SRS alone cannot be used because of the elevated incidence of radiation-induced complications known to be associated with large-volume tumors. With increasing treatment volumes, SRS-associated tumor control rates decrease and complication rates increase. Planned subtotal resection (STR) with adjuvant SRS (adaptive hybrid surgery [AHS]) has gained increasing interest in recent years as a multimodal approach. In AHS, a planned STR (aimed at decreasing surgical morbidity) followed by SRS to a preplanned residual tumor aids in harnessing advantages offered by both approaches. Although intuitive and reasonable, this paradigm shift from maximal resection at all cost has not been adopted widely. Combining open micro¬surgery with SRS requires a good understanding of both surgical and SRS modalities and their respective safety–efficacy features. We present a review and discussion on AHS as a modern, multidisciplinary treatment approach. Available data and views are discussed for vestibular schwannoma (VS) as a sample tumor. Other indications for AHS are mentioned in brief.
  • Less is More: Modern Neonatology

    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.
  • Rare Disease Diagnostics: A Single-center Experience and Lessons Learnt

    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.
  • An Algorithm for Improving Hospital Performance Measures: A Department-centered Approach

    In recent years, it has become increasingly important to improve efficiency and economic balance in hospitals. The department chairperson (or Chair) contends with a production function consisting of inputs and outcomes, rife with managerial constraints. These constraints can be reduced with proper management by diverting resources and activity. Lack of a proper management algorithm at the department level is a significant impediment to improving operational efficiency in hospitals without significant additional costs. In this work we aimed to develop and implement a management algorithm in a teaching hospital department, in order to improve performances and quality of care. From September 2012 to December 2017 we developed a novel management algorithm for a surgical department and implemented it in the Head and Neck Surgery Department at Rambam Medical Center, Haifa, Israel. Changes were made to the organization structure and the concept of service provision. We defined core measures reflecting operative actions and outcomes and identified actions that could affect these measures. Based on our analysis of outcomes we constructed a management intervention process that defines operative actions leading to improved performance. The result was over 400% improvement in the department’s outcome measures including quality, activity, and service. Analysis of data from the Israeli Ministry of Health revealed that the department’s ranking in performance measures and volume improved from no. 14 of 23 departments in Israel in 2011, to no. 1 in 2013, which was sustained through 2014–2016. Improvement in efficiency also translated to economic balance and transformation from deficit to profitability. If this algorithm is implemented in the rest of the system, it is expected to improve the function of the hospital as a whole. Our results have the potential to foster the development of a new organizational culture of measurement and improvement in the hospital, and subsequently in the entire health system.
  • Management of Breathlessness in Palliative Care: Inhalers and Dyspnea—A Literature Review

    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.
  • Bone Involvement in Hyperphosphatemic Familial Tumoral Calcinosis: A New Phenotypic Presentation

    Mutations in FGF23, KL, and GALNT3 have been identified as the cause for the development of hyperphosphatemic familial tumoral calcinosis (HFTC). Patients with HFTC typically present in childhood or adolescence with periarticular soft tissue deposits that eventually progress to disrupt normal joint articulation. Mutations in the GALNT3 gene were shown to account for the hyperphosphatemic state in both HFTC and hyperostosis-hyperphosphatemia syndrome (HHS), the latter characterized by bone involvement. We present the case of a patient of a Druze ethnic origin with known HFTC that presented to our department with the first documented case of pathologic fracture occurring secondary to the disease. Our report introduces this new phenotypic presentation, suggests a potential role for prophylactic bone screening, and highlights the need for preconception genetic screening in selected populations.
  • Clinical Characteristics and Prognosis of Idiopathic Acute Pancreatitis

    Objective: Acute pancreatitis is a serious diagnosis with an increasing incidence in the Western world. In this study we sought to investigate the incidence of idiopathic AP and to compare clinical and prognostic characteristics of idiopathic cases with cases of AP with known etiology. Methods: In this retrospective study of adult hospitalized patients diagnosed with acute pancreatitis between 2012 and 2015, a comparison was made between admissions of patients with known etiology and those for whom no cause was found. Primary outcome was defined as composite outcome of 30-day mortality and complications. Results: Among 560 admissions of 437 patients with a primary diagnosis of acute pancreatitis, the main factors identified were gallstones (51.2%) and idiopathic pancreatitis (35.9%), with alcohol ranked third at only 4.8%. Mortality rate within 30 days of hospitalization was 2.9% and within one year was 7.1%. Use of lipid-lowering, anti-hypertensive, and anti-diabetic medications was more frequent among patients with “idiopathic” disease (70%, 68%, and 33% versus 59%, 56%, and 27%, respectively). Patients admitted with idiopathic AP, in comparison to patients with known AP etiology, had milder disease with shorter hospital stay (3 days versus 4, respectively), and less re-admission in 30 days (7.5% versus 21.2%). Idiopathic AP patients had better prognosis in terms of 30-day death and complication (HR 0.33, 95% CI 0.08–0.40, P<0.001). Conclusion: Idiopathic disease is common among acute pancreatitis patients; the two study groups differed in severity of disease and prognosis. Common use of medications with doubtful value suggests possible under-diagnosis of drug-induced acute idiopathic pancreatitis.
  • Is the Rotavirus Vaccine Really Associated with a Decreased Risk of Developing Celiac and Other Autoimmune Diseases?

    This review examines the risk of developing celiac disease (CD) and other autoimmune diseases in individ¬uals receiving the rotavirus (RV) vaccine compared to the normal population. Celiac disease is a malabsorp¬tive, chronic, immune-mediated enteropathy involving the small intestine. The pathogenesis of CD is multifactorial, and mucosal immunity plays an important role in its development. Low mucosal IgA levels significantly increase the risk of developing the disease. Rotavirus is an infectious agent that causes diar¬rhea, particularly in children aged 0–24 months, and is frequently involved in diarrhea-related deaths in these children. An oral vaccine against RV has been developed. While it is effective on RV infection, it also contributes to increasing mucosal immunity. Studies have indicated that individuals immunized with the RV vaccine are at lower risk of developing CD than unvaccinated individuals. In addition, the mean age for developing CD autoimmunity may be higher in the vaccinated group than in controls receiving placebo. Additional studies that include children immunized with different RV vaccines and unvaccinated children would provide more meaningful results. Although current data suggest a possible association of RV vaccina¬tion with a reduced risk of developing CD and other autoimmune diseases, this remains an unanswered question that merits greater international investigation.
  • Impact of an Integrated Yoga Therapy Protocol on Insulin Resistance and Glycemic Control in Patients with Type 2 Diabetes Mellitus

    Objective: Diabetes mellitus (DM), characterized by chronic hyperglycemia, is attributed to relative insulin deficiency or resistance, or both. Studies have shown that yoga can modulate parameters of insulin resis¬tance. The present study explored the possible beneficial effects of integrated yoga therapy with reference to glycemic control and insulin resistance (IR) in individuals with diabetes maintained on standard oral medical care with yoga therapy, compared to those on standard oral medical care alone. Methods: In this study, the subjects on yoga intervention comprised 35 type 2 diabetics, and an equal number of volunteers constituted the control group. Subjects ranged in age from 30 to 70 years, with hemoglobin A1c (HbA1c) test more than 7%, and were maintained on diabetic diet and oral hypoglycemic agents. Blood samples were drawn prior to and after 120 days of integrated yoga therapy intervention. Fasting blood glucose (FBG), post-prandial blood glucose (PPBG), HbA1c, insulin, and lipid profile were assessed in both the intervention and control groups. Results: The intervention group revealed significant improvements in body mass index (BMI) (0.7 kg/m2 median decrease; P=0.001), FBG (20 mg/dL median decrease; P<0.001), PPBG (33 mg/dL median decrease; P<0.001), HbA1c (0.4% median decrease; P<0.001), homeostatic model assessment for insulin resistance (HOMA-IR) (1.2 median decrease; P<0.001), cholesterol (13 mg/dL median decrease, P=0.006), triacylglycerol (22 mg/dL median decrease; P=0.027), low-density lipo¬protein (6 mg/dL median decrease; P=0.004), and very-low-density lipoprotein levels (4 mg/dL median decrease; P=0.032). Increases in high-density lipoprotein after 120 days were not significant (6 mg/dL median increase; P=0.15). However, when compared to changes observed in patients in the control group, all these improvements proved to be significant. Conclusion: Administration of integrated yoga therapy to individuals with diabetes leads to a significant improvement in glycemic control, insulin resistance, and key biochemical parameters.
  • Medieval Roots of the Myth of Jewish Male Menstruation

    The Jews in Western Europe during the middle ages were often perceived as distinct from other people not only in their religion, but also by virtue of peculiar physical characteristics. Male Jews were circumcised, which made them physically distinct in the sexual realm. They were believed to have a flux of blood due to hemorrhoids that was thought to more abound in Jews because they consumed salty foods and gross undigested blood, and were melancholic. By the late medieval and early modern periods, the male menstru¬ation motif had become closely connected to the theory of the four humors and the balance between bodily fluids. Men in general were thought of as emitting extra heat, whereas women were considered to be phys¬ically cooler. While most men were generally able to reduce their heat naturally, there was a perception that womanish Jewish males were unable to do so, and thereby required “menstruation” (i.e. a literal discharge of blood) in order to achieve bodily equilibrium. The Jewish male image as having menses due to bleeding hemorrhoids was an anti-Semitic claim that had a religious explanation: Jews menstruated because they had been beaten in their hindquarters for having crucified Jesus Christ. This reflection is one of the first biological-racial motifs that were used by the Christians. Preceding this, anti-Semitic rationalizations were mostly religious. However, once these Christians mixed anti-Semitism with science, by emphasizing the metaphorical moral impurity of Jews, the subsequent belief that Jewish men “menstruated” developed—a belief that would have dire historical consequences for the Jewish communities of Europe until even the mid-twentieth century. This topic has direct applicability to current medical practice. The anti-Semitic perspec¬tive of Jewish male menstruation would never have taken hold if the medical community had not ignored the facts, and if the population in general had had a knowledge of the facts. In the same way, it is important for present-day scientists and healthcare professionals to understand thoroughly a topic and not to deliberately ignore the facts, which can affect professional and public thought, thereby leading to incorrect and at times immoral conclusions.