Israel Medical Association Journal

Background: Immune thrombocytopenia (ITP) is an autoimmune disorder of variable origin that results in bleeding and decreased platelet count. Autoimmune abnormalities have been described in patients with malignancies including non-Hodgkin's lymphoma but are rarely described in patients with Hodgkin's lymphoma.

Objectives: To describe an unusual presentation of Hodgkin's lymphoma in an unusual age and alarm pediatricians of the challenging diagnosis.  

Methods: We present two cases that highlight an unusual clinical presentation of childhood Hodgkin's lymphoma occurring at an atypical age.

Results: Over a 4-year period, two children aged 5 and 6 years were admitted for suspected ITP, both had cervical lymphadenopathy. Bone marrow examination showed no evidence of tumor or fibrosis. Biopsy of the lymph node was possible only after administration of intravenous immunoglobulins and normalization of the platelet count. Platelet counts increased after initiation of chemotherapy.

Conclusions: The identification of the clinical presentation of ITP as a possible presentation of Hodgkin's lymphoma is important to facilitate timely diagnosis and management.

Background: Pregestational diabetes mellitus (PGDM) carries a significantly elevated risk of adverse maternal and fetal outcomes. There is evidence that certain interventions reduce the risk for adverse outcomes. Studies have shown that a multi-disciplinary approach improves pregnancy outcomes in women with PGDM.

Objectives: To determine pregnancy outcomes in women with PGDM using a multi-disciplinary approach.

Methods: We retrospectively reviewed consecutive women with pregestational type 1 and type 2 diabetes who were monitored at a high-risk pregnancy clinic at the Sheba Medical Center. Clinical data were obtained from the medical records. All data related to maternal glucose control and insulin pump function were prospectively recorded on Medtronic CareLink® pro software (Medtronic MiniMed, Northridge, CA).

Results: This study comprised 121 neonates from 116 pregnancies of 94 women. In 83% of the pregnancies continuous glucose monitoring (CGM) sensors were applied during a part or all of the pregnancy. Pregnancy outcomes among women who were followed by a multi-disciplinary team before and during pregnancy, and during labor and puerperium resulted in better glucose control (hemoglobin A1c 6.4% vs. 7.8%), lower risk for pregnancy induced hypertension/preeclampsia (7.7% vs. 15.6%), lower birth weight (3212 g vs. 3684 g), and lower rate of large size for gestational age and macrosomia (23.1% vs. 54.2% and 3.3% vs. 28.4%, respectively), compared to data from European cohorts.

Conclusions: The multi-disciplinary approach for treating women with PGDM practiced in the high-risk pregnancy clinic at the Sheba Medical Center resulted in lower rates of macrosomia, LGA, and pregnancy induced hypertension compared to rates reported in the literature.

Background: With the recent introduction of high-sensitivity troponin (hsTn), the incremental benefit of stress myocardial perfusion imaging (MPI) in the evaluation of patients who present to the emergency department (ED) with acute coronary syndrome (ACS) is unclear.

Objectives: To assess the added value of stress MPI in low-risk ACS patients with normal range hsTnI.

Methods: We analyzed all patients who were hospitalized at our medical center from February 2016 to November 2017, who presented with low-risk ACS and underwent stress MPI, and in whom hsTnI was in the normal range after the introduction of hsTnI.

Results: During the study period, 161 patients were admitted with a diagnosis of unstable angina (i.e., ACS with normal range hsTnI) and underwent stress MPI during index admission. The study population included 52/161 patients (31.7%) with low-risk ACS who had no indication for initial invasive strategy. No patients had positive MPI. One patient underwent coronary angiography due to suggestive history; however, he did not have a significant coronary artery disease and had no indication for percutaneous coronary intervention.

Conclusions: In patients with low-risk ACS and normal range hsTnI without additional high-risk features, stress MPI has little additional value for the correct diagnosis and management. Prospective studies are warranted to confirm whether resting hsTnI could serve as a powerful triage tool in chest pain patients in the ED before diagnostic testing and thus, improve patient management.

The output settings of echocardiographic systems should be set to the full (original) frame rate and lossless compression (e.g., run-length encoding) in order to transmit echocardiographic videos so that they retain their original quality. In addition, monitors and display cards of echocardiography systems and workstations should be able to support an adaptive refresh rate for displaying video at an arbitrary frame rate, including a high frame rate (90+ fps) without dropping frames and preserving the original frame duration. Currently, the only available option for echocardiography monitors is 144–165 Hz (or higher) based on adaptive frame rate G-Sync or FreeSync technology monitors. These monitors should be accompanied by compatible display cards. Echocardiography systems and workstation video playback software should support G-Sync or FreeSync adaptive frame rate technology to display echocardiography videos at their original frame rates without the effects of jitter and frame drops. Echocardiography systems should support an online display of the videos on the workstations during acquisition with the original quality. The requirements for web-based workstations are the same as for desktops workstations. Hospital digital networks should provide transmission and long-term archiving of the echocardiographic videos in their original acquisition quality.

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, distinct pulmonary vascular disease, which is caused by chronic obstruction of major pulmonary arteries. CTEPH can be cured by pulmonary endarterectomy (PEA). PEA for CTEPH is a challenging procedure, and patient selection and the perioperative management are complex, requiring significant experience.

Objectives: To describe the establishment of a national CTEPH–PEA center in Israel and present results of surgery.

Methods: In this study, we reviewed the outcomes of PEA in a national referral, multi-disciplinary center for CTEPH–PEA. The center was established by collaborating with a high-volume center in Europe. A multidisciplinary team from our hospital (pulmonary hypertension specialist, cardiac surgeon, cardiac anesthesiologist and cardiac surgery intensivist was trained under the guidance of an experienced team from the European center.

Results: A total of 38 PEA procedures were performed between 2008 and 2018. We included 28 cases in this analysis for which long-term follow-up data were available. There were two hospital deaths (7%). At follow-up, median New York Heart Association (NYHA) class improved from III to I (P < 0.0001), median systolic pulmonary pressure decreased from 64 mmHg to 26 mmHg (P < 0.0001), and significant improvements were seen in right ventricular function and exercise capacity.

Conclusions: A national center for performance of a rare and complex surgical procedure can be successfully established by collaboration with a high-volume center and by training a dedicated multidisciplinary team.

Spinal manipulation therapy (SMT) is commonly used as an effective therapeutic modality for a range of cervical symptoms. However, in rare cases, cervical manipulation may be associated with complications. In this review we present a series of cases with cervical spine injury and myelopathy following therapeutic manipulation of the neck, and examine their clinical course and neurological outcome. We conducted a search for patients who developed neurological symptoms due to cervical spinal cord injury following neck SMT in the database of a spinal unit in a tertiary hospital between the years 2008 and 2018. Patients were assessed for the clinical course and deterioration, type of manipulation used and subsequent management. A total of four patients were identified, two men and two women, aged 32–66 years. In three patients neurological deterioration appeared after chiropractic adjustment and in one patient after tuina therapy. Three patients were managed with anterior cervical discectomy and fusion while one patient declined surgical treatment. Assessment for subjective and objective evidence of cervical myelopathy should be performed prior to cervical manipulation, and suspected myelopathic patients should be sent for further workup by a specialist familiar with cervical myelopathy (such as a neurologist, a neurosurgeon or orthopedic surgeon who specializes in spinal surgery). Nevertheless, manipulation therapy remains an important and generally safe treatment modality for a variety of cervical complaints. This review does not intend to discard the role of SMT as a significant part in the management of patients with neck related symptoms, rather it is meant to draw attention to the need for careful clinical and imaging investigation before treatment.

Background: Although cross-reactions between Epstein-Barr virus (EBV) and human systemic lupus erythematosus (SLE) autoantigens occur, a complete analysis of the potential EBV peptide cross-reactome has not been performed.

Objectives: To analyze the whole EBV proteome searching for peptides common to SLE-related proteins and endowed with an immunological potential.

Methods: Fifty-one SLE-related proteins were analyzed for hexapeptide sharing with EBV proteome using publicly available databases.

Results: An extremely high number of hexapeptides are shared between 34 human SLE autoantigens and EBV proteins. The peptide sharing mostly occurs with complement components C4 and Interleukin-10 (IL-10).

Conclusion: This study thoroughly describes the EBV vs. SLE autoantigens peptide overlap and powerfully supports cross-reactivity as a major mechanism in EBV-associated SLE etiopathogenesis.

Background: Tumor treating fields (TTFields) are low-intensity, intermediate frequency electric fields that affect proliferating cells. TTFields are FDA approved for treatment of newly diagnosed and recurrent glioblastoma. Combining TTFields with immunotherapy is a rational approach due to their different mechanisms of action (MOA) and to the ability of TTFields to induce immunogenic cell death. Conversely, TTFields may interfere with immune functions critical for effective T-cell responses.

Objectives: To evaluate the effects of TTFields on pivotal antitumoral T-cell functions.

Methods: T-cells from healthy donor peripheral blood (PB) or from viably dissociated human glioblastoma samples were cultured under normal or TTFields conditions, with or without superantigen stimulation. Multiparametric flow cytometry (8-color) was used to assess T-cell responses by monitoring select pivotal functions: proliferation (CFSE), IFNγ secretion, cytotoxic degranulation (CD107a), and activation/exhaustion (PD-1). Cellular viability was assessed in a dedicated assay. A chimeric antigen receptor (CAR) T-cell-based assay directly evaluated cellular cytotoxicity.

Results: Activated PB T-cells and tumor-infiltrating T-cells (TILs) preserved all monitored anti- tumoral functions under TTFields, apart from proliferation. This finding also applied specifically to PD-1 + TILs, comprised predominantly of tumor antigen-specific cells. Activated T-cells that attempted to proliferate under TTFields demonstrated decreased viability, in line with TTField MOA. Small or no reduction in viability was found in T-cells that did not attempt to proliferate, whether activated or resting.

Conclusions: All monitored anti-tumoral T cell functions, except for proliferation, were unhindered by TTFields. Our results support further investigation into combinations of TTFields with T-cell based immunotherapeutic approaches.

Background: The sentinel lymph node (SLN) biopsy procedure is a well-known method for identifying solid tumors such as breast cancer, vulvar cancer, and melanoma. In endometrial and cervical cancer, SLN has recently gained acceptance.

Objectives: To evaluate the detection rate of SLN with an indocyanine green and near-infrared fluorescent imaging (ICG/NIR) integrated laparoscopic system in clinically uterine-confined endometrial or cervical cancer.

Methods: Patients with clinically early-stage endometrial or cervical cancer were included in this retrospective study. ICG was injected into the uterine cervix and an ICG/NIR integrated laparoscopic system was used during the surgeries. The National Comprehensive Cancer Network (NCCN) protocol was followed. SLN and/or suspicious lymph nodes were resected. Side-specific lymphadenectomy was performed when mapping was unsuccessful. Systematic lymphadenectomy was completed in patients with high-grade histology or deep myometrial invasion. Enhanced pathology using ultra-staging and immunohistochemistry were performed in all cases.

Results: We analyzed 46 eligible patients: 39 endometrial and 7 cervical cancers. Of these, 44 had at least one SLN (93.6%). In 41 patients (89%) we detected bilateral SLN, in 3 (7%) only unilateral, and in 2 (4%) none were detected. Seven patients presented with lymph node metastasis. All were detected by NCCN/SLN protocol. Of these cases, two were detected with only pathological ultra-staging.

Conclusions: SLN mapping in endometrial and cervical cancer can easily be performed with a high detection rate by integrating ICG/NIR into a conventional laparoscopic system. Precision medicine in patients evaluated by SLN biopsy changes the way patients with endometrial or cervical cancer are managed.

Background: Congenital factor VII deficiency is a rare recessive autosomal bleeding disorder with a wide spectrum of clinical manifestations.

Objectives: To compare the clinical and laboratory findings in Jewish and Bedouin patients with factor VII deficiency.

Methods: The clinical and laboratory findings of patients with factor VII deficiency treated at Soroka Medical Center, a tertiary hospital in Israel, from 2005 to 2015 were analyzed regarding blood factor levels, illness severity, treatment administration, and disease outcome.

Results: Seventy-eight patients were enrolled (1:13,000 of the population in southern Israel) of whom 26 were diagnosed with severe factor VII deficiency (1:40,000). Sixty (76.9%) patients were Jewish and 18 (23.1%) were Bedouin. In univariable analysis, Bedouin patients exhibited a more severe illness, with significantly higher complication and fatality rates, and required more preventive treatment than the Jewish patients.

Conclusions: The prevalence of congenital factor VII deficiency (including severe deficiency) in the Jewish and Bedouin populations of southern Israel is higher than previously reported. The clinical spectrum of the disease was found to be more severe in the Bedouin population.

Background: When a woman with an endometrioma presents with acute abdominal pain, it is unclear whether ovarian torsion should be suspected.

Objectives: To compare patient characteristics, imaging results, and surgical management of endometriomas in elective versus emergent surgeries.

Methods: This retrospective cohort study included women treated at our institution during the period 1990–2015 who presented with histologically verified endometrioma and who underwent either planned surgery or emergent surgery due to suspected adnexal torsion.

Results: Of 225 surgeries performed, 174 were elective and 51 emergent. Patients in the emergent group were significantly younger (33.9 ± 11.1 vs. 39.01 ± 10.9 years, P = 0.004). Abdominal pain was the main complaint of all the emergent surgery patients and the leading complaint in 21% of the elective surgery patients (P < 0.001), with right-sided predominance in both groups. Sonographic parameters were similar in both groups. Bilateral ovarian cysts were noted in 11.7% and 11.0% of emergent and elective patients, respectively (P = 0.87). Laboratory evaluation was notable for a higher white blood cell count and CA125 levels among emergent patients. All patients in the emergent group and 93% of patients in the elective group were managed laparoscopically. No cases of torsion were noted. The rate of intra-pelvic adhesions was similar in both groups (56.8% vs. 66.6%, P = 0.19).

Conclusions: Endometrioma may present with acute abdominal pain. However, adnexal torsion in these patients is rare. These cases can be managed using a minimally invasive approach, assuming an optimal surgical setting.