Harefuah最新文献

Introduction: And yet it moves" - according to tradition, these were Galileo Galilei's defiant words affirming the truth of motion as a fundamental principle of the universe. This image aptly captures the spirit of modern women's medicine, which is itself in constant motion - scientific, technological, and ethical. The field continues to evolve beyond the traditional boundaries of obstetrics and gynecology, embracing a comprehensive view of women's health across the life course. The contemporary "women across the life cycle" model emphasizes that women's health should not be viewed as an isolated event of pregnancy, childbirth, or disease, but rather as a dynamic continuum of biological, psychological, and social processes. This approach calls for a holistic, multidisciplinary, and longitudinal medical perspective that integrates evidence-based science with the ethical values of dignity, autonomy, and equality. Recent decades have brought unprecedented advances in women's health - from artificial intelligence and robotic surgery to fertility innovations and personalized medicine. These developments, while transformative, raise essential questions: how can we preserve humanism, empathy, and compassion within a technologically driven healthcare system? This issue of "Harefuah" presents original research and reviews addressing diverse aspects of women's medicine, from the history of cesarean delivery and contemporary clinical challenges to forward-looking innovations shaping the future of the field. "And yet it moves" thus serves not only as a physical principle, but also as a metaphor for medicine itself - ever moving forward, advancing and evolving, while remaining anchored in humanity.

Introduction: Preeclampsia, one of the Great Obstetrical Syndromes, remains a major contributor to maternal and fetal morbidity worldwide. Its clinical heterogeneity, classically reflected in "early" versus "late" presentations, underscores the need for biologically grounded sub-classifications to guide diagnosis and management.

Objectives: To characterize the cellular and molecular mechanisms underlying preeclampsia subtypes using advanced single-cell and single-nuclei transcriptomic approaches, and to evaluate their alignment with a proposed integrated model distinguishing Type I (placental dysfunction) from Type II (maternal cardiovascular maladaptation) preeclampsia.

Methods: We performed single-cell and single-nuclei RNA sequencing on approximately 90,000 placental cells, encompassing 46 distinct cell populations, including trophoblast, lymphoid, myeloid, stromal, and endothelial lineages. Comparative transcriptomic analyses were conducted between early-onset and late-onset preeclampsia and control pregnancies.

Results: Profound cellular dysregulation was identified in early-onset preeclampsia across multiple placental cell types, consistent with widespread placental dysfunction, angiogenic imbalance, inflammatory response and apoptosis. In contrast, late-onset preeclampsia exhibited comparatively subtle transcriptional changes, suggestive of a distinct pathophysiological process driven by maternal cardiovascular maladaptation, placental aging, cellular senescence and oxidative stress. These findings support the classification of preeclampsia into Type I (placental-dominant, early-onset) and Type II (maternal-dominant, late-onset) forms, each characterized by specific risk factors, biomarkers, and therapeutic targets.

Conclusions: This placental molecular atlas integrates single-cell and single-nuclei transcriptomic data with clinical phenotypes, providing mechanistic support for the Type I and Type II preeclampsia framework. These insights inform the development of targeted interventions, including RNA-based therapies to modulate placental angiogenic pathways in early-onset disease, and maternal cardiovascular optimization strategies in late-onset disease.

Introduction: Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare and life-threatening condition in which tumor cells cause pulmonary microvascular obstruction and pulmonary hypertension. Clinical diagnosis before death is exceptionally uncommon. We present a case of a 51-year-old woman with a history of gastric adenocarcinoma who developed acute respiratory symptoms in the setting of metastatic disease. A combination of imaging findings, laboratory tests, and echocardiography raised clinical suspicion for PTTM and led to the initiation of targeted treatment before pathological confirmation. We discuss the clinical implications as well as diagnostic and therapeutic options for this rare condition.

Introduction: Pulmonary embolism of Cement during percutaneous vertebroplasty.

Background: Monogenic kidney diseases account for approximately one-third of chronic kidney disease (CKD) etiologies in children. Genetic diagnosis enables disease characterization, targeted therapies, long-term prognostic assessment, identification of multisystem involvement, and detection of at-risk relatives. Genetic testing may improve early diagnosis, carrier detection, and prevention of inherited kidney disease in consanguineous populations.

Objectives: To describe the establishment of a nephrogenetic clinic at Soroka Medical Center and to report the diagnostic yield and genetic findings from the first five years of activity.

Methods: Founded in 2019, the clinic is a joint initiative of the Genetics Institute and the Pediatric Nephrology unit. Children with suspected monogenic kidney disease are referred for evaluation. Following a clinical and family history review, a tailored diagnostic workup is conducted, including karyotype, chromosomal microarray, targeted gene panels, or whole exome sequencing (WES). In unresolved cases with a high index of suspicion to genetic etiology, further testing is conducted in a research setting. Results are delivered through genetic counseling, including clinical recommendations. The clinic operates as a multidisciplinary model with coordinated follow-up.

Results: A total of 145 patients were evaluated, including 50 siblings from 20 families. Most were male (58.6%) and of Bedouin origin (80%). Parental consanguinity was reported in 41% of families. Genetic testing was performed in 89 patients (61.4%), identifying a pathogenic or likely pathogenic variants in 76.4%. The most common clinical presentations were tubulopathies (23.4%), cystic or ciliopathy disease (20.7%), nephrolithiasis or nephrocalcinosis (19.3%), and congenital anomalies of the kidney and urinary tract (CAKUT) (13.1%). Three novel variants in C1GALT1C1, PKHD1 and REN genes were identified in the research setting.

Conclusions: The establishment and operation of a dedicated nephrogenetic clinic in a population with a high rate of consanguinity resulted in a diagnostic yield of 76.4% among patients suspected of having monogenic kidney disease. This model has enabled personalized care and reproductive counseling, and may serve as a template for similar initiatives in other high-risk pediatric and adult populations.

Objectives: Cervical cancer stands as the fourth most prevalent malignancy affecting women on a global scale, with its origin predominantly linked to the presence of human papillomavirus (HPV), causing cervical intraepithelial lesions. When high-grade lesions are recognized, it often necessitates an excisional procedure (cervical conization). In women of childbearing age, the impact of conization on pregnancy outcomes remains an area of conflicting evidence. In this study, we compare pregnancy outcomes among women who underwent cervical conization and investigate whether cervical conization heightens the risk of adverse pregnancy outcomes and specifically, the risk for preterm delivery and cesarean delivery.

Methods: This is a retrospective cohort study of women who had undergone cervical conization and had at least one subsequent pregnancy and delivery at the Soroka University Medical Center (SUMC). First, this group of women was compared with a matched cohort (by demographic characteristics such as age, parity and ethnicity with a 4:1 ratio) of women without a history of cervical conization in order to examine pregnancy complications and perinatal outcomes. Later, pregnancy outcomes were compared only among women with cervical conization based on pre- and post-conization characteristics, such as pre-conization PAP results and biopsy results after colposcopy, and post-conization cone size (largest diameter), cervical histology results and endocervical glands involvement.

Results: A total of 78 women who had cervical conization and at least one subsequent pregnancy and delivery were included in the analysis and were later compared with a matched cohort of 312 women without cervical conization. When compared to a matched cohort of women without a cervical conization, women with a cervical conization had an increased risk for preterm premature rupture of membranes (p<0.001) and preterm delivery (p=0.02). Rates of cesarean delivery were significantly higher in women with cervical conization, however, the risk for cesarean section was not increased due to the conization procedure itself. In the study group, we found no significant differences in pregnancy complications or perinatal outcomes between women with cervical conization based on pre- or post-conization characteristics.

Conclusions: Cervical conization procedure was found to be a significant risk factor for preterm premature rupture of membranes and preterm delivery in subsequent pregnancies.

Introduction: The Soroka University Medical Center (SUMC) Emergency Team activity presented here in routine time, periods of transition to emergencies, unto war condition in southern Israel. The SUMC experienced two major events in the Iron Swords War ("Haravot Barzel War"): 1) on the 7th October 2023 violent Hamas attacks against Israelis challenged the SUMC in a mega-mass casualty event (MCE) never seen in Israel; 2) on the 19th June, 2025, an Iranian ballistic missile attack on the surgical building. The SUMC staff treated hundreds of casualties on-site during the first 24 hours, but also dealt with hundreds more going through secondary evacuation to other medical facilities in the country. The SUMC Emergency Headquarters (HQ) worked according to Standards of Procedure (SOP) and specific short Orders of Operations well prepared in advance by the Soroka Emergency Team. Successful handling of such an extraordinary MCE situation required a degree of flexibility of the SUMC management staff and the use of a shared "emergency lexicon". Debriefing principles after all real emergency or training drill events is part of the Soroka Emergency Team duties. After debriefing, lessons are immediately implemented and included in SUMC emergency SOP's - such as the creation of two new emergency treatment areas after the 7.10.2023 MCE.

Introduction: Ocular injuries in combat or field environments, particularly those resulting from shrapnel or blast mechanisms, frequently cause penetrating globe trauma. These injuries pose an immediate and severe threat to ocular integrity and commonly result in significant visual impairment, including blindness or loss of the globe itself. The primary challenge in these scenarios is prompt identification of globe perforation through clinical assessment and imaging, followed by urgent surgical intervention. We report the case of a male patient in his twenties who was urgently referred to our center with suspected scleral perforation of the right eye. Such injuries typically involve intraocular or intraorbital foreign bodies and necessitate emergency surgery under general anesthesia, encompassing wound exploration, foreign body removal, and globe repair. This injury occurred due to an unexpected explosion of a rifle bullet buried beneath a cooking fire ("poike"). High-energy injuries of this nature usually carry a poor prognosis regarding vision and globe preservation. Remarkably, in this case, meticulous clinical examination, precise imaging and appropriate surgical technique, allowed successful management through a relatively minor procedure under local anesthesia. The patient made a full recovery without lasting ocular damage.

Introduction: Early surgical debridement and skin grafting of deep thermal burns are considered one of the cornerstones of modern burn care. Despite improvement in morbidity and long-term outcomes, the drawbacks of surgery include a non-selective debridement, need for an operating room, blood loss, and donor site scars. The first clinical trial with a pineapple-based concentrate of proteolytic enzymes for enzymatic debridement of deep burns was conducted at Soroka University Medical Center in the last 2 decades of the 20th century. As the treatment is selective, it is intended to reduce the need for surgical debridement and skin-grafting, as it spares viable tissue that may have the potential for spontaneous healing. Years later, after the completion of seven clinical trials, NexoBrid enzymatic debridement received its first approval for use by the European Medicines Agency in 2012. Since then, additional clinical trials including two multicenter RCT's were conducted around the world and the treatment is now approved for use in more than 40 countries worldwide. To date more than 14,000 patients have been treated with NexoBrid and more than 150 papers were published since the first clinical trial. We conducted a Pubmed and Google Scholar search for papers including the terms "NexoBrid" or "Bromelain enzymatic debridement" published between 18/12/2012 (European approval) and 1/3/2025, in which 146 relevant papers were found. This article summarizes the main lessons learned from these papers.

Introduction: This issue of Harefuah is dedicated to articles authored by the staff of Soroka University Medical Center, part of the Clalit Health Services group. Soroka is a leading medical center that delivers exceptional quality care to the residents of southern Israel, placing patients and their needs at its center, while also serving as a model for medical education and research. The strategic importance of Soroka for the State of Israel is evident in routine times, however, it becomes even more pronounced during emergencies and security escalations, as experienced in recent years. This was the case: during the October 7th 2023 events, when Soroka teams treated an unprecedented volume of casualties and in the Iron Swords War, when Soroka received the largest number of severely injured Israel Defense Forces (IDF) casualties. This was highlighted during Operation "Rising Lion", when an Iranian ballistic missile struck directly at the heart of the hospital-an event unparalleled in Israel's health system. The articles presented in this issue reflect the breadth of Soroka's work-from the treatment of complex injuries to breakthroughs in genetics, from managing emergencies to pioneering innovative therapies that have spread from the Negev to the farthest corners of the world.