Publications by authors named "Uri Hochberg"

43 Publications

Gender differences in multifidus fatty infiltration and sarcopenia and association with preoperative pain and functional disability in patients with lumbar spinal stenosis.

Spine J 2021 Jun 8. Epub 2021 Jun 8.

Spine Surgery Unit, Neurosurgical Department, Tel Aviv Medical Center, Tel Aviv, Israel. Sackler faculty of medicine, Tel-Aviv University. Electronic address:

Background: In patients with lumbar spinal stenosis, female gender has been associated with higher pain and functional disability. Sarcopenia and multifidus atrophy have also been associated with symptomatic severity.

Purpose: The purpose of this study was to determine if gender differences in sarcopenia and multifidus atrophy are associated with gender disparities in disease symptomatology.

Study Design: Prospectively collected medical records and imaging studies were retrospectively reviewed.

Patient Sample: We retrospectively reviewed medical records and imaging studies for 63 patients with clinically and radiologically defined lumbar spinal stenosis at L3/4 or L4/5 who underwent minimally invasive decompression.

Outcome Measures: Pain and functional disability were measured using the Oswestry Disability Index (ODI) and visual analogue scores for back pain (VASB) and leg pain (VASL).

Methods: Multifidus total cross sectional area (tCSA), multifidus functional cross sectional area (fnCSA), multifidus fatty infiltration (FI), psoas tCSA, and psoas relative cross sectional area (rCSA) were evaluated by univariable and multivariable regression to identify gender linked and gender independent predictors of higher ODI, VASB, and VASL.

Results: Female gender was significantly associated with lower multifidus fnCSA (p < .001), higher multifidus FI (p < .001), lower psoas tCSA (p < .001), lower psoas rCSA (p = .002), and higher preoperative ODI (p = .008). Lower psoas rCSA (p = .044) and psoas tCSA in the lowest sex specific quartile (p = .034) were significantly associated with higher preoperative VASB and psoas rCSA less than the sex specific median (p = .050) was significantly associated with higher preoperative VASL after controlling for age and gender. Multifidus FI was significantly associated with preoperative ODI after adjusting for age (p = .048) but not after controlling additionally for gender (p = .651).

Conclusions: Female patients with lumbar spinal stenosis may develop more severe and functionally significant multifidus atrophy, resulting in a more severe clinical course with higher functional disability. Sarcopenia was significantly associated with higher preoperative back pain and leg pain in both male and female patients with lumbar spinal stenosis.
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http://dx.doi.org/10.1016/j.spinee.2021.06.007DOI Listing
June 2021

Ultrasound-guided retrolaminar cervical block.

Reg Anesth Pain Med 2021 May 24. Epub 2021 May 24.

Department of Anesthesia and Chronic Pain Unit, Hospital Quirónsalud de Tenerife, Santa Cruz de Tenerife, Spain

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http://dx.doi.org/10.1136/rapm-2021-102695DOI Listing
May 2021

Pain Management - A Decade's Perspective of a New Subspecialty.

J Pain Res 2021 9;14:923-930. Epub 2021 Apr 9.

Department of Anesthesiology and Critical Care Medicine, Institute of Pain Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

Objective: Pain management is increasingly recognized as a formal medical subspecialty worldwide. Israel was among the first to offer a board-certified subspecialty, formalized by the Israeli Medical Association in 2010 which is open to all clinicians with a state-recognized specialization. This paper aims at evaluating the current program across several quality control measures.

Design: A survey among pain medicine specialists who graduated from the Israeli Pain Management subspecialty.

Methods: All 43 graduates of the program were sent a web-based questionnaire, each related to a different time in the participants' residency period - prior to, during and after training.

Results: Forty-one physicians responded to the survey (95% response rate). The most common primary specialty was Anesthesiology (44%), followed by Family Medicine (22%). One-third of the respondents applied to the program over five years after completing their initial residency. Two-thirds reported that they acquired all or most of the professional tools required by a pain specialist. Insufficient training was mentioned regarding addiction management (71%), special population needs (54%) and interventional treatment (37%). A high proportion (82%) responded that the examination contributed to their training and almost all perceived their period of subspecialty as having a positive value in their personal development. Two-thirds of respondents had not yet actively engaged beyond the clinical aspect with other entities responsible for formulating guidelines and other strategic decision-making.

Conclusion: We hope the findings of this first-of-a-kind survey will encourage other medical authorities to construct formal training in pain medicine and enable this discipline to further evolve.
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http://dx.doi.org/10.2147/JPR.S303815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044436PMC
April 2021

A New Solution to an Old Problem: Ultrasound-guided Cervical Retrolaminar Injection for Acute Cervical Radicular Pain: Prospective Clinical Pilot Study and Cadaveric Study.

Spine (Phila Pa 1976) 2021 Oct;46(20):1370-1377

Department of Anesthesia and Chronic Pain Unit. Hospital Quirónsalud de Tenerife. Santa Cruz de Tenerife, Spain.

Study Design: Prospective clinical pilot study and cadaveric study.

Objective: The aim of this study was to evaluate the spread of an ultrasound-guided interfascial plane blocks (UGIPBs) and its potential efficacy for cervical radiculopathy.

Summary Of Background Data: Cervical radiculopathy is a common disorder, potentially leading to severe pain and disability. Conservative treatment with cervical epidural steroid injections (ESI) is limited by concerns regarding their safety. UGIPBs are used in cervical surgical procedures as part of the multimodal postoperative analgesia regimen however, were not described for cervical radiculopathy.

Methods: Twelve patients with acute cervical radicular pain who failed conservative treatment and were candidates for surgery were offered a cervical retrolaminar injection. A solution of 4 mL lidocaine 0.5% and 10 mg dexamethasone was injected, assisted by ultrasound guidance, at the posterior aspect of the cervical lamina corresponding to the compressed nerve root level. Additionally, a cadaver study was carried to evaluate the contrast spread and infiltration into near structures, both anatomically and radiographically.

Results: Twelve patients underwent the procedure, with a mean follow-up time of 14.5 weeks. Average numerical rating scale improved from 7.25 at baseline to 2.83 following the injection (P < 0.001). Three patients received 2 to 3 injections without significant improvement and were eventually operated. No adverse events were reported.In the cadaver study, fluoroscopy demonstrated contrast spread between T1 and T3 caudally, C2 to C5 cranially and facet joints laterally. Anatomically, the dye spread was demonstrated up to C2 cranially, T1 caudally, the articular pillars of C4 to C7, and the neural foramen of C6 laterally.

Conclusion: A solution injected into the cervical retrolaminar plane can diffuse in the cranial-caudal axis to C2-T3 and laterally to the facet joints and the cervical neural foramen. Our pilot study confirmed the feasibility of our study protocol. Future studies are needed to support our early results.Level of Evidence: 4.
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http://dx.doi.org/10.1097/BRS.0000000000004024DOI Listing
October 2021

Neuro-axial steroid injection in pain management and COVID-19 vaccine.

Eur J Pain 2021 04 22;25(4):945-946. Epub 2021 Feb 22.

Institute for Pain Medicine, Chaim Sheba Medical Center, Tel Hashomer, Israel.

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http://dx.doi.org/10.1002/ejp.1749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013309PMC
April 2021

An increase in xylem embolism resistance of grapevine leaves during the growing season is coordinated with stomatal regulation, turgor loss point and intervessel pit membranes.

New Phytol 2021 02 19;229(4):1955-1969. Epub 2020 Nov 19.

Institute of Soil, Water and Environmental Science, Volcani Center, Agricultural Research Organization, PO Box 6, Bet-Dagan, 50250, Israel.

Although xylem embolism resistance is traditionally considered as static, we hypothesized that in grapevine (Vitis vinifera) leaf xylem becomes more embolism-resistant over the growing season. We evaluated xylem architecture, turgor loss point (Ψ ) and water potentials leading to 25% of maximal stomatal conductance (g ) or 50% embolism in the leaf xylem (P ) in three irrigation treatments and at three time points during the growing season, while separating the effects of leaf age and time of season. Hydraulic traits acclimated over the growing season in a coordinated manner. Without irrigation, Ψ , g , and P decreased between late May and late August by 0.95, 0.77 and 0.71 MPa, respectively. A seasonal shift in P occurred even in mature leaves, while irrigation had only a mild effect (< 0.2 MPa) on P . Vessel size and pit membrane thickness were also seasonally dynamic, providing a plausible explanation for the shift in P . Our findings provide clear evidence that grapevines can modify their hydraulic traits along a growing season to allow lower xylem water potential, without compromising gas exchange, leaf turgor or xylem integrity. Seasonal changes should be considered when modeling ecosystem vulnerability to drought or comparing datasets acquired at different phenological stages.
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http://dx.doi.org/10.1111/nph.17025DOI Listing
February 2021

Interventional Pain Management for Cancer Pain: An Analysis of Outcomes and Predictors of Clinical Response.

Pain Physician 2020 09;23(5):E451-E460

Cancer Pain Clinic, Division of Supportive and Palliative Care, McGill University Health Centre, Montreal, QC, Canada; Alan Edwards Pain Management Unit, McGill University Health Centre, Montreal, QC, Canada.

Background: Interventional procedures are offered routinely to patients seen in McGill University's interdisciplinary cancer pain management program. However, publications on these procedures are scarce, making it difficult to predict which patients may benefit from them.

Objectives: We hypothesized that interventional pain procedures offered to cancer patients could provide relief of pain as well as other symptoms. Furthermore, some variables may predict the efficacy of such procedures.

Study Design: We conducted a retrospective chart review of interventional pain management procedures.

Setting: The procedures reviewed were conducted at the Cancer Pain Program and performed at the interventional suites of the McGill University Health Centre.

Methods: The retrospective chart review included interventional pain management procedures performed between June 2015 and March 2017. Demographic data, details about the underlying cancer and about the procedure and peripTrocedural patients' reported outcomes were recorded for analysis.

Results: Eighty-two of 126 procedures were included for analysis. Most patients presented with metastatic disease (75%). Eighty percent of the patients reported pain relief, with the average pain severity decreasing by more than 2 points on a 0-to-10 Numeric Rating Scale for pain (from 6.5 of 10 to 4.2 of 10). Forty-three percent of patients were considered responders (>= 50% pain relief). Responders also reported a significant decrease in fatigue, depression, anxiety, drowsiness, and improved well-being. Among responders, average daily opioid use decreased significantly, by 60% on average. None of the analyzed variables correlated with the response; however, psychosocial variables like anxiety and depression showed a nonsignificant trend towards predicting procedure failure.

Limitations: The core limitations of this study are its size and retrospective nature.

Conclusions: In this cohort of cancer pain patients, interventional cancer pain procedures provided effective pain relief and other benefits, including pain relief, reduced burden of symptoms, and reduction of opioid intake, while demonstrating a favorable safety profile. Patients with poorer ratings of depression and fatigue derived less benefit from procedures, suggesting that offering such procedures as part of patients' treatment plan would be sensible, rather than leaving interventions for later stages.
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September 2020

Tailoring of neurosurgical ablative procedures in the management of refractory cancer pain.

Reg Anesth Pain Med 2020 09 22;45(9):696-701. Epub 2020 Jul 22.

Tel Aviv University Sackler School of Medicine, Tel Aviv, Israel.

Introduction: Neurosurgical ablative procedures can offer immediate and effective pain relief for patients suffering from refractory cancer pain. However, choosing the appropriate procedure for each patient may not be straightforward and warrants an interdisciplinary approach. The purpose of the current study was to evaluate the outcome of patients with cancer who were carefully selected for neurosurgical intervention by a dedicated interdisciplinary team composed of a palliative physician and nurse practitioner, a pain specialist and a neurosurgeon.

Methods: A retrospective review was carried out on all patients who underwent neurosurgical ablative procedures in our institute between March 2015 and September 2019. All patients had advanced metastatic cancer with unfavorable prognosis and suffered from intractable oncological pain. Each treatment plan was devised to address the patients' specific pain syndromes.

Results: A total of 204 patients were examined by our service during the study period. Sixty-four patients with localized pain and nineteen patients with diffuse pain syndromes were selected for neurosurgical interventions, either targeted disconnection of the spinothalamic tract or stereotactic cingulotomy. Substantial pain relief was reported by both groups immediately (cordotomy: Numerical Rating Scale (NRS) 9 ≥1, p=0.001, cingulotomy: NRS 9 ≥2, p=0.001) and maintained along the next 3-month follow-up visits.

Conclusions: An interdisciplinary collaboration designated to provide neurosurgical ablative procedures among carefully selected patients could culminate in substantial relief of intractable cancer pain.

Trial Registration Number: IR0354-17.
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http://dx.doi.org/10.1136/rapm-2020-101566DOI Listing
September 2020

Leaf Carbon Export and Nonstructural Carbohydrates in Relation to Diurnal Water Dynamics in Mature Oak Trees.

Plant Physiol 2020 08 29;183(4):1612-1621. Epub 2020 May 29.

Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts 02138.

Trees typically experience large diurnal depressions in water potential, which may impede carbon export from leaves during the day because the xylem is the source of water for the phloem. As water potential becomes more negative, higher phloem osmotic concentrations are needed to draw water in from the xylem. Generating this high concentration of sugar in the phloem is particularly an issue for the ∼50% of trees that exhibit passive loading. These ideas motivate the hypothesis that carbon export in woody plants occurs predominantly at night, with sugars that accumulate during the day assisting in mesophyll turgor maintenance or being converted to starch. To test this, diurnal and seasonal patterns of leaf nonstructural carbohydrates, photosynthesis, solute, and water potential were measured, and carbon export was estimated in leaves of five mature (>20 m tall) red oak () trees, a species characterized as a passive loader. Export occurred throughout the day at equal or higher rates than at night despite a decrease in water potential to -1.8 MPa at midday. Suc and starch accumulated over the course of the day, with Suc contributing ∼50% of the 0.4 MPa diurnal osmotic adjustment. As a result of this diurnal osmotic adjustment, estimates of midday turgor were always >0.7 MPa. These findings illustrate the robustness of phloem functioning despite diurnal fluctuations in leaf water potential and the role of nonstructural carbohydrates in leaf turgor maintenance.
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http://dx.doi.org/10.1104/pp.20.00426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401141PMC
August 2020

Peng block in prosthetic hip replacement: A cadaveric radiological evaluation.

J Clin Anesth 2020 10 21;65:109888. Epub 2020 May 21.

Department of Anesthesia Hospital Universitario de Móstoles, Madrid, Spain.

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http://dx.doi.org/10.1016/j.jclinane.2020.109888DOI Listing
October 2020

The physiology of drought stress in grapevine: towards an integrative definition of drought tolerance.

J Exp Bot 2020 08;71(16):4658-4676

Wine Research Centre, Faculty of Land and Food Systems, The University of British Columbia, Vancouver, BC, Canada.

Water availability is arguably the most important environmental factor limiting crop growth and productivity. Erratic precipitation patterns and increased temperatures resulting from climate change will likely make drought events more frequent in many regions, increasing the demand on freshwater resources and creating major challenges for agriculture. Addressing these challenges through increased irrigation is not always a sustainable solution so there is a growing need to identify and/or breed drought-tolerant crop varieties in order to maintain sustainability in the context of climate change. Grapevine (Vitis vinifera), a major fruit crop of economic importance, has emerged as a model perennial fruit crop for the study of drought tolerance. This review synthesizes the most recent results on grapevine drought responses, the impact of water deficit on fruit yield and composition, and the identification of drought-tolerant varieties. Given the existing gaps in our knowledge of the mechanisms underlying grapevine drought responses, we aim to answer the following question: how can we move towards a more integrative definition of grapevine drought tolerance?
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http://dx.doi.org/10.1093/jxb/eraa245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7410189PMC
August 2020

Letter to the Editor: A survey on the position of Israeli pain specialists on the adequate diagnosis and treatment of myofascial pain.

J Bodyw Mov Ther 2019 07 22;23(3):441-442. Epub 2019 Mar 22.

Institute of Pain Medicine, Department of Anesthesia and Critical Care Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address:

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http://dx.doi.org/10.1016/j.jbmt.2019.03.009DOI Listing
July 2019

Neurosurgical ablative procedures for intractable cancer pain.

J Neurosurg 2019 May 10:1-8. Epub 2019 May 10.

1Department of Neurosurgery.

OBJECTIVECancer patients suffering from severe refractory pain may benefit from targeted ablative neurosurgical procedures aimed to disconnect pain pathways in the spinal cord or the brain. These patients often present with a plethora of medical problems requiring careful consideration before surgical interventions. The authors present their experience at an interdisciplinary clinic aimed to facilitate appropriate patient selection for neurosurgical procedures, and the outcome of these interventions.METHODSThis study was a retrospective review of all patients who underwent neurosurgical interventions for cancer pain in the authors' hospital between March 2015 and April 2018. All patients had advanced metastatic cancer with limited life expectancy and suffered from intractable oncological pain.RESULTSSixty patients underwent surgery during the study period. Forty-three patients with localized pain underwent disconnection of the spinal pain pathways: 34 percutaneous-cervical and 5 open-thoracic cordotomies, 2 stereotactic mesencephalotomies, and 2 midline myelotomies. Thirty-nine of 42 patients (93%) who completed these procedures had excellent immediate postoperative pain relief. At 1 month the improvement was maintained in 30/36 patients (83%) available for follow-up. There was 1 case of hemiparesis.Twenty patients with diffuse pain underwent stereotactic cingulotomy. Nineteen of these patients reported substantial pain relief immediately after the operation. At 1 month good pain relief was maintained in 13/17 patients (76%) available for follow-up, and good pain relief was also found at 3 months in 7/11 patients (64%). There was no major morbidity or mortality.CONCLUSIONSWith careful patient selection and tailoring of the appropriate procedure to the patient's pain syndrome, the authors' experience indicates that neurosurgical procedures are safe and effective in alleviating suffering in patients with intractable cancer pain.
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http://dx.doi.org/10.3171/2019.2.JNS183159DOI Listing
May 2019

Visualizing Embolism Propagation in Gas-Injected Leaves.

Plant Physiol 2019 06 6;180(2):874-881. Epub 2019 Mar 6.

Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts 02138.

Because the xylem in leaves is thought to be at the greatest risk of cavitation, reliable and efficient methods to characterize leaf xylem vulnerability are of interest. We report a method to generate leaf xylem vulnerability curves (VCs) by gas injection. Using optical light transmission, we visualized embolism propagation in grapevine () and red oak () leaves injected with positive gas pressure. This resulted in a rapid, stepwise reduction of transmitted light, identical to that observed during leaf dehydration, confirming that the optical method detects gas bubbles and provides insights into the air-seeding hypothesis. In red oak, xylem VCs generated using gas injection were similar to those generated using bench dehydration, but indicated 50% loss of conductivity at lower tension (∼0.4 MPa) in grapevine. In determining VC, this method eliminates the need to ascertain xylem tension, thus avoiding potential errors in water potential estimations. It is also much faster (1 h per VC). However, severing the petiole and applying high-pressure gas could affect air-seeding and the generated VC. We discuss potential artifacts arising from gas injection and recommend comparison of this method with a more standard procedure before it is assumed to be suitable for a given species.
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http://dx.doi.org/10.1104/pp.18.01284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6548249PMC
June 2019

Swift metabolite changes and leaf shedding are milestones in the acclimation process of grapevine under prolonged water stress.

BMC Plant Biol 2019 Feb 11;19(1):69. Epub 2019 Feb 11.

The French Associates Institute for Agriculture and Biotechnology of Drylands, The Jacob Blaustein Institute for Desert Research, Ben-Gurion University of the Negev, Sede Boqer campus, Midreshet Ben Gurion, Israel.

Background: Grape leaves provide the biochemical substrates for berry development. Thus, understanding the regulation of grapevine leaf metabolism can aid in discerning processes fundamental to fruit development and berry quality. Here, the temporal alterations in leaf metabolism in Merlot grapevine grown under sufficient irrigation and water deficit were monitored from veraison until harvest.

Results: The vines mediated water stress gradually and involving multiple strategies: osmotic adjustment, transcript-metabolite alteration and leaf shedding. Initially stomatal conductance and leaf water potential showed a steep decrease together with the induction of stress related metabolism, e.g. up-regulation of proline and GABA metabolism and stress related sugars, and the down-regulation of developmental processes. Later, progressive soil drying was associated with an incremental contribution of Ca and sucrose to the osmotic adjustment concomitant with the initiation of leaf shedding. Last, towards harvest under progressive stress conditions following leaf shedding, incremental changes in leaf water potential were measured, while the magnitude of perturbation in leaf metabolism lessened.

Conclusions: The data present evidence that over time grapevine acclimation to water stress diversifies in temporal responses encompassing the alteration of central metabolism and gene expression, osmotic adjustments and reduction in leaf area. Together these processes mitigate leaf water stress and aid in maintaining the berry-ripening program.
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http://dx.doi.org/10.1186/s12870-019-1652-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6371445PMC
February 2019

Retrograde Intrathecal Drug Delivery: A Report of Three Cases for the Management of Cancer-Related Sacropelvic Pain.

J Pain Palliat Care Pharmacother 2018 Jun - Sep;32(2-3):149-154. Epub 2018 Dec 27.

We report three cases of sacral and pelvic pain resistant to oral medications successfully managed with intraspinal drug delivery through a catheter placed at the intrathecal sacral space to deliver low doses of bupivacaine and fentanyl with local effects.
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http://dx.doi.org/10.1080/15360288.2018.1491927DOI Listing
August 2019

An Internet-Based Survey to Assess Clinicians' Knowledge and Attitudes Towards Opioid-Induced Hypogonadism.

Pain Pract 2019 02 2;19(2):176-182. Epub 2018 Dec 2.

Alan Edwards Pain Management Unit, McGill University Health Centre, Montreal, Quebec, Canada.

Background: Long-term opioid therapy for chronic pain management requires regularly assessing and documenting benefits and side effects. Opioid-induced sex hormone disturbances are a complication that needs to be assessed routinely and perhaps not only when suspected. There is abundant literature about its prevalence, clinical consequences, and treatment, yet routine hormone screening and appropriate treatment are seldom performed in pain clinics. Ignorance, skepticism, and/or indifference are possible reasons explaining why opioid-induced hypogonadism (OIH) remains underdiagnosed among chronic pain patients.

Methods: This was an Internet-based survey reaching out to pain clinicians to assess their knowledge and attitudes regarding OIH.

Results: A total of 135 responses were received, representing a 23.7% response rate. Analysis of responses showed that 47% of responders were somewhat familiar with this complication, but their knowledge about the prevalence and the time to develop varied. Screening for OIH is ordered based on suspicion of its presence (50%), but not routinely (38%). Lack of knowledge was the most frequent reason adduced for not screening for OIH. Sex-related symptoms and signs are the most relevant reasons leading to suspicion and screening of OIH. Upon laboratory confirmation, most responders refer their patients to endocrinology (82%) for further management since most (60%) believe that testosterone replacement would improve their patients' health.

Conclusions: Knowledge and attitudes towards OIH varied among this population of pain clinicians invited to participate in the research. Lack of knowledge and incertitude seem to impact the attitudes towards screening and treating OIH. Better medical training at undergraduate and postgraduate levels as well as continuous medical education may contribute to raising awareness about this complication and providing early treatment.
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http://dx.doi.org/10.1111/papr.12731DOI Listing
February 2019

[NEUROSURGICAL INTERVENTIONS FOR INTRACTABLE ONCOLOGICAL PAIN].

Harefuah 2018 Feb;157(2):108-111

The Department of Neurosurgery, Tel Aviv Medical Center, Tel Aviv.

Introduction: Pain is one of the most common symptoms among cancer patients, and particularly in those who suffer from metastatic or terminal disease. There is great importance in delivering good pain management to these patients in order to alleviate their suffering, improve their functional status and their overall quality of life. In most cases, pain management is based on pharmacotherapy with opioids and other medications. However, there are selected patients for whom pharmacotherapy does not achieve acceptable pain relief or is associated with marked side effects. These patients, who suffer from refractory cancer pain, may benefit from neurosurgical procedures selectively intervening in different locations along the pain signaling pathways. This article summarizes several of these neurosurgical procedures: percutaneous cordotomy for unilateral pain, punctuate midline myelotomy for visceral pain and stereotactic cingulotomy for diffuse pain syndromes. This article demonstrates the use of careful patient selection by an interdisciplinary team which is critical for the success of these procedures. The team consists of palliative care specialists, pain specialists and a neurosurgeon. These neurosurgical interventions are presented through representative clinical cases, followed by a discussion of the clinical considerations that guided the choice of the therapeutic approach for each case.
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February 2018

New frontier: cancer pain management clinical fellowship.

Support Care Cancer 2018 Jul 10;26(7):2453-2457. Epub 2018 Feb 10.

Division of Supportive and Palliative Care, McGill University Health Centre, Montreal, QC, Canada.

Cancer pain is a multi-dimensional experience, varies from person to person both physically and psycho-socially, and impacts all aspects of the patients' quality of life. Majority of patients with an advanced or metastatic cancer will experience pain. It is estimated that as many as half of cancer patients are under-treated and as many as 20% experience pain refractory to the conventional WHO ladder of pain management. The McGill University Health Centre (MUHC) Cancer Pain Clinic (CPC) was created to meet the needs of those patients with a diagnosis of cancer whose pain had become a main symptom and those who failed to respond to conventional treatment. The clinic offers a unique interdisciplinary approach with a core team that includes an anesthesiologist, a palliative care physician, a radiation oncologist, a nurse clinician specialist in oncology and palliative care, and, recently, also an interventional radiologist. A cancer pain clinical fellowship was offered for the first time in July 2016. It provides intense training in the classification, epidemiology, pathophysiology, and treatment of cancer pain. Through our education program, the fellow learns to appreciate, weigh, and respond to the full spectrum of factors influencing a specific patient's condition and to develop a tailor-made care plan. To our knowledge, it is the only fellowship program in existence that focuses exclusively on cancer pain. We see it as a beacon and hope that our graduate fellows become professional leaders with a quest not only to provide the best possible care but also to raise awareness of the humanitarian need to control cancer pain.
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http://dx.doi.org/10.1007/s00520-018-4085-5DOI Listing
July 2018

Double Anterior Stereotactic Cingulotomy for Intractable Oncological Pain.

Stereotact Funct Neurosurg 2017 10;95(6):400-408. Epub 2018 Jan 10.

Department of Neurosurgery, Division of Neurosurgery, Tel Aviv Medical Center, Tel Aviv, Israel.

Background: Stereotactic anterior cingulotomy has been used in the treatment of patients suffering from refractory oncological pain due to its effects on pain perception. However, the optimal targets as well as suitable candidates and outcome measures have not been well defined. We report our initial experience in the ablation of 2 cingulotomy targets on each side and the use of the Brief Pain Inventory (BPI) as a perioperative assessment tool.

Methods: A retrospective review of all patients who underwent stereotactic anterior cingulotomy in our Department between November 2015 and February 2017 was performed. All patients had advanced metastatic cancer with limited prognosis and suffered from intractable oncological pain.

Results: Thirteen patients (10 women and 3 men) underwent 14 cingulotomy procedures. Their mean age was 54 ± 14 years. All patients reported substantial pain relief immediately after the operation. Out of the 6 preoperatively bedridden patients, 3 started ambulating shortly after. At the 1-month follow-up, the mean preoperative Visual Analogue Scale score decreased from 9 ± 0.9 to 4 ± 2.7 (p = 0.003). Mean BPI pain severity and interference scores decreased from levels of 29 ± 4 and 55 ± 12 to 16 ± 12 (p = 0.028) and 37 ± 15 (p = 0.043), respectively. During the 1- and 3-month follow-up visits, 9/11 patients (82%) and 5/7 patients (71%) available for follow-up reported substantial pain relief. No patient reported worsening of pain during the study period. Neuropsychological analyses of 6 patients showed stable cognitive functions with a mild nonsignificant decline in focused attention and executive functions. Adverse events included transient confusion or mild apathy in 5 patients (38%) lasting 1-4 weeks.

Conclusions: Our initial experience indicates that double stereotactic cingulotomy is safe and effective in alleviating refractory oncological pain.
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http://dx.doi.org/10.1159/000484613DOI Listing
December 2018

O-Arm-Guided Percutaneous Radiofrequency Cordotomy.

Stereotact Funct Neurosurg 2017 10;95(6):409-416. Epub 2018 Jan 10.

Department of Neurosurgery, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

Background: Pain is often one of the most debilitating symptoms in patients with advanced oncological disease. Patients with localized pain due to malignancy refractory to medical treatment can benefit from selective percutaneous cordotomy that disconnects the ascending pain fibers in the spinothalamic tract.

Objectives: Over the past year, we have been performing percutaneous radiofrequency cordotomy with the use of the O-Arm intraoperative imaging system that allows both 2D fluoroscopy and 3D reconstructed computerized tomography imaging. We present our experience using this technique, focusing on technical nuances and complications.

Methods: A retrospective analysis was conducted of all patients who underwent percutaneous cordotomy between March 2016 and March 2017.

Results: Nineteen patients underwent percutaneous cordotomy procedures. Two patients developed intraoperative delirium and were unable to tolerate the procedure. In 16 out of 17 completed procedures, we achieved excellent immediate pain relief (94%). At 1 month after operation, 15 of the 17 (88%) patients were pain free, and at 3 months 5 out of 5 patients available for follow-up were still free of their original pain. Mirror pain developed in 6 of the 17 patients (35%), but was mild in 4 of these cases and controlled with medications. We experienced 1 serious complication (6%) of ipsilateral hemiparesis.

Conclusion: Percutaneous cordotomy using the O-Arm is safe and effective in the treatment of intractable oncological pain.
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http://dx.doi.org/10.1159/000484614DOI Listing
December 2018

Iso/Anisohydry: A Plant-Environment Interaction Rather Than a Simple Hydraulic Trait.

Trends Plant Sci 2018 02 6;23(2):112-120. Epub 2017 Dec 6.

UCA, INRA, PIAF, 63000 Clermont-Ferrand, France.

Plants are frequently classified as isohydric or anisohydric in an attempt to portray their water relations strategy or ecological niche. However, despite the popularity of the iso/anisohydric classification, the underlying biology remains unclear. We use here a simple hydraulic model and the extensive literature on grapevine hydraulics to illustrate that the iso/anisohydric classification of a plant depends on the definition used and the environment in which it is grown, rather than describing an intrinsic property of the plant itself. We argue that abandoning the iso/anisohydric terminology and returning to a more fundamental hydraulic framework would provide a stronger foundation for species comparisons and ecological predictions.
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http://dx.doi.org/10.1016/j.tplants.2017.11.002DOI Listing
February 2018

The potential of the spectral 'water balance index' (WABI) for crop irrigation scheduling.

New Phytol 2017 Nov 10;216(3):741-757. Epub 2017 Aug 10.

The French Associates Institute for Agriculture and Biotechnology of Drylands, The Jacob Blaustein Institutes for Desert Research, Ben-Gurion University of the Negev, Midreshet Ben-Gurion, 84990, Israel.

Hyperspectral sensing can detect slight changes in plant physiology, and may offer a faster and nondestructive alternative for water status monitoring. This premise was tested in the current study using a narrow-band 'water balance index' (WABI), which is based on independent changes in leaf water content (1500 nm) and the efficiency of the nonphotochemical quenching (NPQ) photo-protective mechanism (531 nm). The hydraulic, photo-protective and spectral behaviors of five important crops - grapevine, corn, tomato, pea and sunflower - were evaluated under water deficit conditions in order to associate the differences in stress physiology with WABI suitability. Rapid alterations in both leaf water content and NPQ were observed in grapevine, pea and sunflower, and were effectively captured by WABI. Apart from water status monitoring, the index was also successful in scheduling the irrigation of a vineyard, despite phenological and environmental variability. Conversely, corn and tomato displayed a relatively strict stomatal regime and/or mild NPQ responses and were, thus, unsuitable for WABI-based monitoring. WABI shows great potential for irrigation scheduling of various crops, and has a clear advantage over spectral models that focus on either of the abovementioned physiological mechanisms.
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http://dx.doi.org/10.1111/nph.14718DOI Listing
November 2017

Grape Metabolic Response to Postveraison Water Deficit Is Affected by Interseason Weather Variability.

J Agric Food Chem 2017 Jul 12;65(29):5868-5878. Epub 2017 Jul 12.

Department of Agricultural, Food, Environmental and Animal Sciences, University of Udine , 33100 Udine, Italy.

Postveraison water deficit is a common strategy implemented to improve fruit composition in many wine-growing regions. However, contrasting results are often reported on fruit size and composition, a challenge for generalizing the positive impact of this technique. Our research investigated the effect of water deficit (WD) imposed at veraison on Merlot grapevines, during two experimental seasons (2014-2015). In both years WD resulted in reduced carbon assimilation rates and leaf shedding. However, the treatment effect on the analyzed berry parameters varied between seasons. Modification of skin metabolites was more evident in 2015 than in 2014, despite the similar soil water content and water stress physiological parameters (gas exchange, water potential) recorded in the two experimental years. Higher solar radiation and air temperature in 2015 than in 2014 hint for the involvement of atmospheric parameters in fulfilling the potential effect of WD. Our results suggest that the interaction between water availability and weather conditions plays a crucial role in modulating the grape berry composition.
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http://dx.doi.org/10.1021/acs.jafc.7b01466DOI Listing
July 2017

Increased Sympathetic Outflow Induces Adaptation to Acute Experimental Pain.

Pain Pract 2018 03 9;18(3):322-330. Epub 2017 Aug 9.

Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

Background: There are interrelationships between the autonomic nervous system and pain. This study aims to explore the effect of different autonomic manipulations on pain perception and modulation.

Methods: Twenty healthy subjects (10 men and 10 women, mean age 25 ± 3 years) participated in this single-blinded, semi-randomized, controlled study, which included 2 study visits. Warm detection thresholds, heat pain thresholds, conditioned pain modulation (CPM), and pain adaptation were tested before and after administration of phenylephrine, clonidine, yohimbine, and saline.

Results: Changes in heart rate and blood pressure were found after all the pharmacological interventions. The only effect on pain measures was that yohimbine enhanced pain adaptation capacity while phenylephrine reduced it (P = 0.032). Several significant correlations were found between autonomic and pain parameters; greater decreases in heart rate after phenylephrine were associated with reduced pain ratings (r = 0.288, P = 0.018). In addition, enhanced pain adaptation was associated with higher total vascular resistance (r = 0.442, P = 0.01).

Conclusions: Different effects of acute autonomic manipulations on experimental pain were found: an increase in sympathetic tone induced by yohimbine led to reduced pain sensitivity; a decrease in sympathetic tone with no effect on vagal-parasympathetic tone induced by phenylephrine led to reduction in pain adaptation capacity; and a decrease in sympathetic tone and increase in vagal parasympathetic tone by clonidine led to no change in pain adaptation capacity. While increased sympathetic outflow does facilitate pain adaptation, activation of either the sympathetic or parasympathetic limbs of the autonomic nervous system does not affect pain thresholds or CPM. Finally, a correlation exists between nociception and cardiovascular parameters only due to baroreflex activation.
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http://dx.doi.org/10.1111/papr.12606DOI Listing
March 2018

Stomatal Closure, Basal Leaf Embolism, and Shedding Protect the Hydraulic Integrity of Grape Stems.

Plant Physiol 2017 Jun 28;174(2):764-775. Epub 2017 Mar 28.

Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts 02138 (U.H., A.P., Y.-J.Z., J.G., F.E.R., N.M.H.); and.

The time scale of stomatal closure and xylem cavitation during plant dehydration, as well as the fate of embolized organs, are under debate, largely due to methodological limitations in the evaluation of embolism. While some argue that complete stomatal closure precedes the occurrence of embolism, others believe that the two are contemporaneous processes that are accompanied by daily xylem refilling. Here, we utilize an optical light transmission method to continuously monitor xylem cavitation in leaves of dehydrating grapevine () in concert with stomatal conductance and stem and petiole hydraulic measurements. Magnetic resonance imaging was used to continuously monitor xylem cavitation and flow rates in the stem of an intact vine during 10 d of dehydration. The results showed that complete stomatal closure preceded the appearance of embolism in the leaves and the stem by several days. Basal leaves were more vulnerable to xylem embolism than apical leaves and, once embolized, were shed, thereby preventing further water loss and protecting the hydraulic integrity of younger leaves and the stem. As a result, embolism in the stem was minimal even when drought led to complete leaf shedding. These findings suggest that grapevine avoids xylem embolism rather than tolerates it.
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http://dx.doi.org/10.1104/pp.16.01816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5462014PMC
June 2017

Interventional Analgesic Management of Lung Cancer Pain.

Front Oncol 2017 14;7:17. Epub 2017 Feb 14.

Cancer Pain Program, McGill University Health Centre, Montreal, QC, Canada; Alan Edwards Pain Management Unit, McGill University Health Centre, Montreal, QC, Canada.

Lung cancer is one of the four most prevalent cancers worldwide. Comprehensive patient care includes not only adherence to clinical guidelines to control and when possible cure the disease but also appropriate symptom control. Pain is one of the most prevalent symptoms in patients diagnosed with lung cancer; it can arise from local invasion of chest structures or metastatic disease invading bones, nerves, or other anatomical structures potentially painful. Pain can also be a consequence of therapeutic approaches like surgery, chemotherapy, or radiotherapy. Conventional medical management of cancer pain includes prescription of opioids and coadjuvants at doses sufficient to control the symptoms without causing severe drug effects. When an adequate pharmacological medical management fails to provide satisfactory analgesia or when it causes limiting side effects, interventional cancer pain techniques may be considered. Interventional pain management is devoted to the use of invasive techniques such as joint injections, nerve blocks and/or neurolysis, neuromodulation, and cement augmentation techniques to provide diagnosis and treatment of pain syndromes resistant to conventional medical management. Advantages of interventional approaches include better analgesic outcomes without experiencing drug-related side effects and potential for opioid reduction thus avoiding central side effects. This review will describe various pain syndromes frequently described in lung cancer patients and those interventional techniques potentially indicated for those cases.
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http://dx.doi.org/10.3389/fonc.2017.00017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5306685PMC
February 2017

Grapevine acclimation to water deficit: the adjustment of stomatal and hydraulic conductance differs from petiole embolism vulnerability.

Planta 2017 Jun 18;245(6):1091-1104. Epub 2017 Feb 18.

Department of Agricultural, Food, Environmental and Animal Sciences, University of Udine, Via delle Scienze 206, 33100, Udine, Italy.

Main Conclusion: Drought-acclimated vines maintained higher gas exchange compared to irrigated controls under water deficit; this effect is associated with modified leaf turgor but not with improved petiole vulnerability to cavitation. A key feature for the prosperity of plants under changing environments is the plasticity of their hydraulic system. In the present research we studied the hydraulic regulation in grapevines (Vitis vinifera L.) that were first acclimated for 39 days to well-watered (WW), sustained water deficit (SD), or transient-cycles of dehydration-rehydration-water deficit (TD) conditions, and then subjected to varying degrees of drought. Vine development under SD led to the smallest leaves and petioles, but the TD vines had the smallest mean xylem vessel and calculated specific conductivity (k ). Unexpectedly, both the water deficit acclimation treatments resulted in vines more vulnerable to cavitation in comparison to WW, possibly as a result of developmental differences or cavitation fatigue. When exposed to drought, the SD vines maintained the highest stomatal (g ) and leaf conductance (k ) under low stem water potential (Ψ), despite their high xylem vulnerability and in agreement with their lower turgor loss point (Ψ). These findings suggest that the down-regulation of k and g is not associated with embolism, and the ability of drought-acclimated vines to maintain hydraulic conductance and gas exchange under stressed conditions is more likely associated with the leaf turgor and membrane permeability.
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http://dx.doi.org/10.1007/s00425-017-2662-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5432590PMC
June 2017

Pain Modulation and Autonomic Function: The Effect of Clonidine.

Pain Med 2016 Jul;17(7):1292-1301

Department of Internal Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

Objective: The α2-agonist clonidine is an analgesic agent, whose yet uncertain action may involve either increase in pain modulation efficiency, change in autonomic function, and/or decrease in anxiety level. The present study aimed to examine the effect of oral clonidine on pain perception in healthy subjects in order to reveal its mode of action.

Design: Randomized, double-blind, placebo-controlled study.

Subjects: Forty healthy subjects.

Methods: Subjects received either 0.15 mg oral clonidine or placebo. We measured pain parameters of heat pain thresholds, tonic heat stimulus, mechanical temporal summation, offset analgesia (OA) and conditioned pain modulation (CPM); autonomic parameters of deep breathing ratio and heart rate variability indices obtained before, during, and after tonic heat stimulus; and psychological parameters of anxiety and pain catastrophizing.

Results: Clonidine decreased systolic blood pressure (P = 0.022) and heart rate (P = 0.004) and increased rMSSD (P = 0.020), though no effect was observed on pain perception, pain modulation, and psychological parameters. Autonomic changes were correlated with pain modulation capacity; for OA, the separate slope model was significant (P = 0.008); in the clonidine group, more efficient OA was associated with lower heart rate (r = 0.633, P = 0.005), unlike in the placebo group.

Conclusions: The change in autonomic function that was related to the increase in pain modulation capacity, and the lack of change in anxiety, suggest a combined modulatory-autonomic mode of analgesic action for clonidine.
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http://dx.doi.org/10.1093/pm/pnv102DOI Listing
July 2016
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