[CUFFING PRISONERS AND DETAINEES IN ISRAELI HOSPITALS - A MULTI-CENTER STUDY].

AIMS: To describe the extent of prisoner/detainee cuffing and characterize cuffing methods. BACKGROUND: Thousands of prisoners and detainees receive medical treatment in Israeli hospitals every year. According to the Israeli law, cuffing during hospital stay should be an exceptional measure, to be considered only in cases of real threat of violence or escape, based on individual assessment. There is no documentation of cuffing rates in hospitals. METHODS: A multi-center study in 12 hospitals was performed during 2020-2021. Data were collected prospectively or retrieved retrospectively from security records, when available. RESULTS: A total of 1857 prisoners/detainees were documented, of whom 1794 (96.6%) were cuffed. Of the 241 hospitalized patients, 230 (95.4%) were cuffed. Details regarding cuffing methods were available for 185 hospitalized patients, revealing that at least 63 patients (68% of patients for whom details regarding cuffing to bed were available) were cuffed to the bed with opposite arm and leg in a cross position. Cuffing rates of prisoners under custody of the Prisons Authority, police and the Israeli Defense Forces, were 98.5%, 96.6%, and 83%, respectively. Impaired mobility for medical reasons was documented in 64 cases, of whom 85.9% were cuffed regardless. CONCLUSIONS: Cuffing of prisoners/detainees in Israeli hospitals is performed non-selectively, in violation of the law. During hospitalization, cuffing is usually performed in a cross position, severely impairing mobility. Our findings highlight the need for routine documentation of cuffing due to its medical consequences and the responsibility of medical staff towards patients according to rules of ethics and regulations.

Ethics of sharing medical knowledge with the community: is the physician responsible for medical outreach during a pandemic?

A recent update to the Geneva Declaration's 'Physician Pledge' involves the ethical requirement of physicians to share medical knowledge for the benefit of patients and healthcare. With the spread of COVID-19, pockets exist in every country with different viral expressions. In the Chareidi ('ultra-orthodox') religious community, for example, rates of COVID-19 transmission and dissemination are above average compared with other communities within the same countries. While viral spread in densely populated communities is common during pandemics, several reasons have been suggested to explain the blatant flouting of public health regulations. It is easy to fault the Chareidi population for their proliferation of COVID-19, partly due to their avoidance of social media and internet aversion. However, the question remains: who is to blame for their community crisis? The ethical argument suggests that from a public health perspective, the physician needs to reach out and share medical knowledge with the community. The public's best interests are critical in a pandemic and should supersede any considerations of cultural differences. By all indications, therefore, the physician has an ethical obligation to promote population healthcare and share medical knowledge based on ethical concepts of beneficence, non-maleficence, utilitarian ethics as well as social, procedural and distributive justice. This includes the ethical duty to reduce health disparities and convey the message that individual responsibility for health has repercussions within the context of broader social accountability. Creative channels are clearly demanded for this ethical challenge, including measured medical paternalism with appropriate cultural sensitivity in physician community outreach.

Israeli Position Paper: Triage Decisions for Severely Ill Patients During the COVID-19 Pandemic. Joint Commission of the Israel National Bioethics Council, the Ethics Bureau of the Israel Medical Association and Representatives from the Israeli Ministry of Health.

OBJECTIVES: This document provides an English translation of the Israeli Joint Commission's national guidelines for triaging severely ill patients during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Four subcommittees of medical, legal, ethical-social, and religious experts developed the general principles and practical medical criteria for triaging scarce life-saving resources. RESULTS: The guidelines provide an overview of general principles as well as pragmatic medical criteria and a practical triage protocol to be followed should the healthcare system be overwhelmed due to COVID-19. Issues covered include triggers for activating the guidelines, guiding ethical, legal, and religious principles, equity in access, fair distribution, transparency, consistency, palliation, medical policy prioritization, problem-solving mechanisms, and public trust. CONCLUSIONS: The Israeli consensus document and pragmatic medical triage protocol offer a societal and medical roadmap for allocating scarce resources during the COVID-19 pandemic or other disasters.

Characterizing excised breast masses in children and adolescents-Can a more aggressive pathology be predicted?

PURPOSE: Our aim was to characterize excised breast masses in children and adolescent and to identify factors associated with a more aggressive pathology. METHODS: Retrospective review of all female patients <19 who underwent excision of breast masses at our institution between 1999 and 2018. Demographic, clinical, imaging, pathological and management data were collected. We assessed possible association of any of the variables with a more aggressive pathology (phyllodes tumor and malignancy). Correlation between core needle biopsy results and final pathology results was also calculated. RESULTS: 70 patients were included. Median age was 17 years (range: 11-19). Resected mass size was 4 cm (range: 2-16). Final pathology results were: fibroadenoma (49), juvenile fibroadenoma (7), hamartoma (5), benign phyllodes (7), malignant phyllodes (1) and sarcoma (1). Pathology was benign in 61 (87%) patients and more aggressive (phyllodes and sarcoma) in 9 (13%). None of the tested variables was associated with a more aggressive pathology. Presurgical core biopsy results matched final pathology in only 63.6%. CONCLUSIONS: Excised breast masses in children and adolescents are sometimes of a more aggressive pathology, which cannot be predicted by presurgical factors, including a core needle biopsy. Prognosis study LEVEL OF EVIDENCE: III.

Truth-telling and doctor-assisted death as perceived by Israeli physicians.

BACKGROUND: Medicine has undergone substantial changes in the way medical dilemmas are being dealt with. Here we explore the attitude of Israeli physicians to two debatable dilemmas: disclosing the full truth to patients about a poor medical prognosis, and assisting terminally ill patients in ending their lives. METHODS: Attitudes towards medico-ethical dilemmas were examined through a nationwide online survey conducted among members of the Israeli Medical Association, yielding 2926 responses. RESULTS: Close to 60% of the respondents supported doctor-assisted death, while one third rejected it. Half of the respondents opposed disclosure of the full truth about a poor medical prognosis, and the others supported it. Support for truth-telling was higher among younger physicians, and support for doctor-assisted death was higher among females and among physicians practicing in hospitals. One quarter of respondents supported both truth-telling and assisted death, thereby exhibiting respect for patients' autonomy. This approach characterizes younger doctors and is less frequent among general practitioners. Another quarter of the respondents rejected truth-telling, yet supported assisted death, thereby manifesting compassionate pragmatism. This was associated with medical education, being more frequent among doctors educated in Israel, than those educated abroad. All this suggests that both personal attributes and professional experience affect attitudes of physicians to ethical questions. CONCLUSIONS: Examination of attitudes to two debatable medical dilemmas allowed portrayal of the multi-faceted medico-ethical scene in Israel. Moreover, this study, demonstrates that one can probe the ethical atmosphere of a given medical community, at various time points by using a few carefully selected questions.

An intraoperative MRI system for margin assessment in breast conserving surgery: Initial results from a novel technique.

BACKGROUND AND OBJECTIVES: One of the major unmet needs in Breast Conserving Surgery (BCS) is a rapid and accurate margin assessment of the lumpectomy specimen. This study evaluates the ability of a novel MRI system (prototype of the ClearSight™ system; Clear-Cut Medical Ltd., Rehovot, Israel) to distinguish malignant and non-malignant tissues in freshly excised breast specimen by comparing MR measurements to histopathology results. METHODS: Seventy-seven samples were obtained from 22 patients undergoing BCS enrolled in the study. A T2* (T2 Star) value in milliseconds (ms) was calculated for each sample and correlated with histopathology results. RESULTS: Of the 77 samples, 35 samples were classified by histopathology as malignant and 42 as non-malignant. T2* values were significantly higher in malignant samples compared to non-malignant samples (15.3 ± 2.72 ms and 10.6 ± 1.47 ms, respectively [P < 0.00001]). Analysis for a determined cutoff of 11.7 ms revealed 91% sensitivity, 93% specificity, and 92% accuracy. ROC curve analysis yielded AUC of 0.97. CONCLUSIONS: This study demonstrates that the system is sensitive and specific in differentiating malignant and non-malignant tissues in freshly excised breast specimen. The system has the potential to be used for breast specimen margin assessment during BCS, with the goal of decreasing the need for re-operation. J. Surg. Oncol. 2016;114:22-26. © 2016 Wiley Periodicals, Inc.

Skin-sparing mastectomy flap ischemia salvage using urgent hyperbaric chamber oxygen therapy: a case report.

Since its introduction in 1991, skin-sparing mastectomy has emerged as an acceptable surgical technique in the management of breast cancer patients, providing optimal oncological safety and efficacy with favorable aesthetic results. Rates of native skin flap ischemia and necrosis after skin-sparing mastectomy are 2%-30% and result in a decreased aesthetic outcome and delay of necessary adjuvant treatment. Hyperbaric oxygen therapy has been advocated for the management of various compromised flaps, and when instituted immediately postoperatively, may prevent progression of ischemia into necrosis. We report the case of a 41-year-old female who developed skin flap ischemia after undergoing skin-sparing mastectomy and was immediately treated with hyperbaric oxygen. The patient received a total of five hyperbaric oxygen therapy sessions, achieving full resolution of the ischemia without any complications. Further research is essential to determine the role of hyperbaric oxygen therapy in managing skin flap ischemia post skin-sparing mastectomy. Until such studies exist, hyperbaric oxygen therapy may be considered a preferred option in the management of native skin flap ischemia after skin-sparing mastectomy.

Tissue specific DNA methylation in normal human breast epithelium and in breast cancer.

Cancer is a heterogeneous and tissue-specific disease. Thus, the tissue of origin reflects on the natural history of the disease and dictates the therapeutic approach. It is suggested that tissue differentiation, mediated mostly by epigenetic modifications, could guide tissue-specific susceptibility and protective mechanisms against cancer. Here we studied breast specific methylation in purified normal epithelium and its reflection in breast cancers. We established genome wide methylation profiles of various normal epithelial tissues and identified 110 genes that were differentially methylated in normal breast epithelium. A number of these genes also showed methylation alterations in breast cancers. We elaborated on one of them, TRIM29 (ATDC), and showed that its promoter was hypo-methylated in normal breast epithelium and heavily methylated in other normal epithelial tissues. Moreover, in breast carcinomas methylation increased and expression decreased whereas the reverse was noted for multiple other carcinomas. Interestingly, TRIM29 regulation in breast tumors clustered according to the PAM50 classification. Thus, it was repressed in the estrogen receptor positive tumors, particularly in the more proliferative luminal B subtype. This goes in line with previous reports indicating tumor suppressive activity of TRIM29 in estrogen receptor positive luminal breast cells in contrast to oncogenic function in pancreatic and lung cancers. Overall, these findings emphasize the linkage between breast specific epigenetic regulation and tissue specificity of cancer.

A randomized prospective study of lumpectomy margin assessment with use of MarginProbe in patients with nonpalpable breast malignancies.

BACKGROUND: The presence of tumor cells at the margins of breast lumpectomy specimens is associated with an increased risk of ipsilateral tumor recurrence. Twenty to 30 % of patients undergoing breast-conserving surgery require second procedures to achieve negative margins. This study evaluated the adjunctive use of the MarginProbe device (Dune Medical Devices Ltd, Caesarea, Israel) in providing real-time intraoperative assessment of lumpectomy margins. METHODS: This multicenter randomized trial enrolled patients with nonpalpable breast malignancies. The study evaluated MarginProbe use in addition to standard intraoperative methods for margin assessment. After specimen removal and inspection, patients were randomized to device or control arms. In the device arm, MarginProbe was used to examine the main lumpectomy specimens and direct additional excision of positive margins. Intraoperative imaging was used in both arms; no intraoperative pathology assessment was permitted. RESULTS: In total, 596 patients were enrolled. False-negative rates were 24.8 and 66.1 % and false-positive rates were 53.6 and 16.6 % in the device and control arms, respectively. All positive margins on positive main specimens were resected in 62 % (101 of 163) of cases in the device arm, versus 22 % (33 of 147) in the control arm (p < 0.001). A total of 19.8 % (59 of 298) of patients in the device arm underwent a reexcision procedure compared with 25.8 % (77 of 298) in the control arm (6 % absolute, 23 % relative reduction). The difference in tissue volume removed was not significant. CONCLUSIONS: Adjunctive use of the MarginProbe device during breast-conserving surgery improved surgeons' ability to identify and resect positive lumpectomy margins in the absence of intraoperative pathology assessment, reducing the number of patients requiring reexcision. MarginProbe may aid performance of breast-conserving surgery by reducing the burden of reexcision procedures for patients and the health care system.

A similar cell-specific pattern of HOXA methylation in normal and in cancer tissues.

HOX genes are developmental genes that determine anterior-posterior embryonic pattern and govern the process of differentiation. Inappropriate expression of HOX genes has been implicated in developmental abnormalities and hematopoietic malignancies. In addition, HOX genes silencing by DNA methylation has been reported in cancers and related to disease aggressiveness and outcome. On the other hand, accumulating evidence suggests that epigenetic changes at HOX genes are linked to normal development and differentiation. To better understand the relationship between HOXA methylation and cancer, we analyzed the methylation pattern of HOXA genes in human primary breast and colon carcinomas, normal tissues, and normal white blood cells. Genome-wide methylation arrays of breast cancers and white blood cells demonstrated similar methylation patterns. Quantitative methylation analysis of seven representative HOXA genes revealed various levels of methylation in both normal tissues and cancers. Analysis of epithelial-enriched normal breast tissue and stroma indicated that the stroma was the major origin of HOXA methylation. Furthermore, in selected dense breast cancers, minimal increase in methylation of several HOXA genes did not correlate with the predominance of malignant epithelial cells in these tumors. Our results suggest that methylation of the HOXA cluster may be a normal developmental and cell type specific process rather than a cancer specific mechanism.

Diagnostic performance of a novel device for real-time margin assessment in lumpectomy specimens.

BACKGROUND: Margin status in breast lumpectomy procedures is a prognostic factor for local recurrence and the need to obtain clear margins is often a cause for repeated surgical procedures. A recently developed device for real-time intraoperative margin assessment (MarginProbe; Dune Medical Devices, Caesarea, Israel), was clinically tested. The work presented here looks at the diagnostic performance of the device. METHODS: The device was applied to freshly excised lumpectomy and mastectomy specimens at specific tissue measurement sites. These measurement sites were accurately marked, cut out, and sent for histopathologic analysis. Device readings (positive or negative) were compared with histology findings (namely malignant, containing any microscopically detected tumor, or nonmalignant) on a per measurement site basis. The sensitivity and specificity of the device was computed for the full dataset and for additional relevant subgroups. RESULTS: A total of 869 tissue measurement sites were obtained from 76 patients, 753 were analyzed, of which 165 were cancerous and 588 were nonmalignant. Device performance on relatively homogeneous sites was: sensitivity 1.00 (95% CI: 0.85-1), specificity 0.87 (95% CI: 0.83-0.90). Performance for the full dataset was: sensitivity 0.70 (95% CI: 0.63-0.77), specificity 0.70 (95% CI: 0.67-0.74). Device sensitivity was estimated to change from 56% to 97% as the cancer feature size increased from 0.7 mm to 6.6 mm. Detection rate of samples containing pure DCIS clusters was not different from rates of samples containing IDC. CONCLUSIONS: The device has high sensitivity and specificity in distinguishing between normal and cancer tissue even down to small cancer features.

A prospective, randomized, controlled, multicenter study of a real-time, intraoperative probe for positive margin detection in breast-conserving surgery.

BACKGROUND: This randomized, double-arm trial was designed to study the benefit of a novel device (MarginProbe, Dune Medical Devices, Caesarea, Israel) in intraoperative margin assessment for breast-conserving surgery (BCS) and the associated reduction in reoperations. METHODS: In the device group, the probe was applied to the lumpectomy specimen and additional tissue was excised according to device readings. Study arms were compared by reoperation rates and by correct surgical reaction confirmed by histology. RESULTS: Three hundred patients were enrolled. Device use was associated with improved correct surgical reaction, defined as additional re-excision in all histologically detected positive margins, with tumor within 1 mm of inked margin. The repeat lumpectomy rate was significantly reduced by 56% in the device arm: 5.6% versus 12.7% in the control arm. There were no differences in excised tissue volume or cosmetic outcome. CONCLUSIONS: Intraoperative use of the MarginProbe for positive margin detection is safe and effective in BCS and decreases the rate of repeat operations.

A device for real-time, intraoperative margin assessment in breast-conservation surgery.

BACKGROUND: This trial was designed to study performance of a novel handheld probe (Dune Medical Devices, Caesarea, Israel) in intraoperative detection of positive margins and its potential benefit toward minimizing the positive margin rate. METHODS: The probe was intraoperatively applied to 57 lumpectomy specimens. Surgeons were blinded to device output, and surgical decisions were not affected by probe data. Probe readings were compared with histological analysis per margin and per patient. RESULTS: Nineteen of 22 (86%) pathology-positive patients were intraoperatively detected with device use. Per-margin sensitivity was .71, and specificity was .68, maintained within a range of positive margin definitions (0-.4 cm). CONCLUSIONS: The device is an effective tool for intraoperative detection of positive margins with the potential for significant positive margin rate reduction.