Retinochoroiditis secondary to Rickettsia typhi infection: a case report.

BACKGROUND: To report a case of unusual presentation of retinochoroiditis caused by Rickettsia typhi in a patient without prior uveitis. CASE PRESENTATION: In this case, we describe a 24-year-old male soldier with no previous eye disease, who was referred to our ophthalmology department due to bilateral retinochoroiditis and vitritis. The patient initially presented with a paracentral scotoma in his right eye persisting for 7 days and scattered dark spots in his left eye for 2 days in June 2023. Preceding these ocular symptoms, he experienced a two-week episode of fever, headaches, night sweats, and rapid weight loss of 10 kg. A transient rash covered his body briefly. His mother had a history of recurrent eye inflammation. Physical examination revealed bilateral keratic precipitates on the lower corneal periphery, 1 + anterior vitreous cells, small retinal lesions and mild optic discs elevation. Fluorescein angiography indicated mild discs hyperfluorescence, and the clinically visible round punctate lesions on OCT showed inner retinal hyper-reflective lesion with a depth till outer plexiform layer possibly suggestive of a retinitis lesion. Laboratory tests were normal except thrombocytosis, elevated ESR, liver enzymes and ACE levels, with positive Rickettsia typhi serology tests. Rheumatology and infectious disease consultations ruled out autoimmune diseases, confirming Rickettsia typhi infection. Treatment included systemic doxycycline and prednisone, with improvement of visual acuity, ocular symptoms, OCT abnormalities and resolution of inflammation. Prednisone was discontinued, and after two months, additional improvement was seen clinically, with preserved retinal structures on OCT. CONCLUSION: This study explores retinochoroiditis as a rare ocular presentation of Rickettsia typhi, an unusual infection in the Middle East. Previously reported ocular manifestations include conjunctivitis, vitritis, post infectious optic neuropathy and a few cases of uveitis. Ocular symptoms followed systemic illness, highlighting the need for awareness among clinicians. Diagnosis relies on seroconversion, with fluorescein angiography and OCT aiding in assessment. Empiric doxycycline and systemic corticosteroid therapy is recommended. Ocular symptoms resolved in two months. Awareness of these ocular manifestations is essential for timely diagnosis and management. Further research is needed to fully understand this aspect of murine typhus.

Circulating isomiRs May Be Superior Biomarkers Compared to Their Corresponding miRNAs: A Pilot Biomarker Study of Using isomiR-Ome to Detect Coronary Calcium-Based Cardiovascular Risk in Patients with NAFLD.

Circulating miRNAs are increasingly being considered as biomarkers in various medical contexts, but the value of analyzing isomiRs (isoforms of canonical miRNA sequences) has not frequently been assessed. Here we hypothesize that an in-depth analysis of the full circulating miRNA landscape could identify specific isomiRs that are stronger biomarkers, compared to their corresponding miRNA, for identifying increased CV risk in patients with non-alcoholic fatty liver disease (NAFLD)-a clinical unmet need. Plasma miRNAs were sequenced with next-generation sequencing (NGS). Liver fat content was measured with magnetic-resonance spectrometry (MRS); CV risk was determined, beyond using traditional biomarkers, by a CT-based measurement of coronary artery calcium (CAC) score and the calculation of a CAC score-based CV-risk percentile (CAC-CV%). This pilot study included n = 13 patients, age > 45 years, with an MRS-measured liver fat content of ≥5% (wt/wt), and free of overt CVD. NGS identified 1103 miRNAs and 404,022 different isomiRs, of which 280 (25%) and 1418 (0.35%), respectively, passed an abundance threshold. Eighteen (sixteen/two) circulating miRNAs correlated positively/negatively, respectively, with CAC-CV%, nine of which also significantly discriminated between high/low CV risk through ROC-AUC analysis. IsomiR-ome analyses uncovered 67 isomiRs highly correlated (R ≥ 0.55) with CAC-CV%. Specific isomiRs of miRNAs 101-3p, 144-3p, 421, and 484 exhibited stronger associations with CAC-CV% compared to their corresponding miRNA. Additionally, while miRNAs 140-3p, 223-3p, 30e-5p, and 342-3p did not correlate with CAC-CV%, specific isomiRs with altered seed sequences exhibited a strong correlation with coronary atherosclerosis burden. Their predicted isomiRs-specific targets were uniquely enriched (compared to their canonical miRNA sequence) in CV Disease (CVD)-related pathways. Two of the isomiRs exhibited discriminative ROC-AUC, and another two showed a correlation with reverse cholesterol transport from cholesterol-loaded macrophages to ApoB-depleted plasma. In summary, we propose a pipeline for exploring circulating isomiR-ome as an approach to uncover novel and strong CVD biomarkers.

Molecularly Confirmed Female Donor-Transmitted Lobular Breast Cancer to Male following Renal Transplantation.

INTRODUCTION: Lobular breast cancer represents 10%-15% of breast cancers in women but is virtually nonexistent in men, related to the typical absence of the anatomic breast lobule structure in male breast tissue. We describe donor-transmitted metastatic lobular carcinoma to a male after kidney transplantation. Determining whether a post-transplant cancer is transplant associated, donor transmitted, or donor derived is significant for treatment, prognosis, and possibly management of other organ recipients. CASE REPORT: A 74-year-old Caucasian male presented to the emergency department with lower abdominal pain and macro-hematuria. Past medical history included two renal transplantations. Computed tomography identified a 4-5-cm space-occupying lesion in the native left kidney. A left native nephrectomy was performed. Histology pathologic examination demonstrated lobular (as opposed to ductal) breast carcinoma. Fluorescent in situ hybridization probes to identify X- and Y-chromosomes showed tumor cells with an XX genotype, whereas the surrounding host cells were of XY genotype. These findings confirmed the female-sex origin (donor) of the tumor within the XY native male (current patient) tissues. DISCUSSION/CONCLUSION: Due to discordance between the donor and recipient sex, fluorescent in situ hybridization as a molecular technique correctly identified the origin of an individual's cancer in the post-transplant setting. The metastatic breast cancer behaved more indolently than usually seen. Expanded criteria donors (ECD) are those who cannot donate under standard criteria for organ transplantation; expanded criteria widen the potential organ donor pool at the expense of increased risk for post-transplant complications (e.g., graft failure, the transmission of malignancy). The case provides a potential area of future research into considering allowing ECDs with a distant history of cancer with very low transmission risk when the biochemical environment of the recipient would, in the unlikely event of transmission, induce the tumor to pursue an indolent clinical course.

Prognostic significance of pretreatment thrombocytosis in endometrial cancer: an Israeli Gynecologic Oncology Group study.

OBJECTIVE: Endometrial cancer prognosis is related to stage, histology, myometrial invasion, and lymphovascular space invasion. Several studies have examined the association between pretreatment thrombocytosis and patient outcomes with contrasting results regarding prognosis. Our aim was to evaluate the association of pretreatment platelet count with outcomes in endometrial cancer patients. METHODS: This is an Israeli Gynecologic Oncology Group multicenter retrospective cohort study of consecutive patients with endometrial cancer, who underwent surgery between January 2002 and December 2014. Patients were grouped as low risk (endometrioid G1-G2 and villoglandular) and high risk (endometrioid G3, uterine serous papillary carcinoma, clear cell carcinoma, and carcinosarcoma). Those with stage I disease were compared with stages II-IV. Disease stages were reviewed and updated to reflect International Federation of Gynecology and Obstetrics (FIGO) 2009 staging. All patients underwent pelvic washings for cytology and total abdominal or laparoscopic hysterectomy with bilateral salpingo-oophorectomy. Pelvic lymph node assessment was performed in patients with tumors of moderate-high risk histology or deep myometrial invasion. Para-aortic sampling was performed at the surgeon's discretion. Patients were categorized by pretreatment platelet count into two groups: ≤400×109/L and >400×109/L (defined as thrombocytosis). Clinical and pathological features were compared using Student t-test, χ2 or Fisher's exact test. Survival measures were plotted with the Kaplan-Meier method and compared using the log-rank test. A Cox proportional hazards model was used for multivariable comparison of associations. RESULTS: Of the 1482 patients included, most had stage I disease (961; 74.8%) and most had endometrioid histology (927; 64.1%). A total of 1392 patients (94%) had pretreatment platelet counts ≤400×109/L and 90 (6%) had pretreatment thrombocytosis. Patients with thrombocytosis had a significantly higher rate of high-grade malignancy, advanced stage, lymphovascular space invasion, low uterine segment involvement, and lymph node metastases. They also had shorter 5 year disease-free survival (65% vs 80%, p=0.003), disease-specific survival (63% vs 83%, p<0.05) and overall survival (59% vs 77%, p<0.05). On multivariate analysis, an elevated pretreatment thrombocyte count remained a significant independent predictor for disease-specific survival and overall survival. CONCLUSIONS: Pretreatment thrombocytosis is an independent prognostic factor for decreased disease-specific survival and overall survival among patients with endometrial cancer, and can serve as a predictor of poor outcome.

Age is an independent predictor of outcome in endometrial cancer patients: An Israeli Gynecology Oncology Group cohort study.

INTRODUCTION: Advanced age is considered an adverse factor in endometrial cancers but may be a surrogate for other conditions that impact outcomes. The study objective was to assess the association of age with endometrial cancer features, treatment and prognosis. MATERIAL AND METHODS: In this multicenter cohort study, consecutive women with endometrial cancer treated at 10 Israeli institutions between 2000 and 2014 were accrued in an assimilated database. Postmenopausal women were stratified into age groups with a cut-off of 80. Clinical, pathological and treatment data were compared using t test or Mann-Whitney test for continuous variables, and Chi-square Test or Fisher's Exact test for categorical variables. Main outcome measures included disease recurrence and disease-specific and overall survival; these were plotted using the Kaplan-Meier method and compared using the log-rank test. The association between age and recurrence and survival, adjusted for other clinical and pathological factors, was assessed using multivariable Cox regression modeling. RESULTS: A total of 1764 postmenopausal women with endometrial cancer were identified. Adverse pathological features were more prevalent in older women, including high-risk histologies (35% vs 27%, P = .025), deep myoinvasion (44% vs 29%, P = .001) and lymphovascular involvement (22% vs 15%, P = .024). Surgical staging was performed less frequently among older women (33% vs 56%; P < .001). Chemotherapy was less often prescribed, even for non-endometrioid histologies (72% vs 45%; P < .001). On multivariable analysis, age remained a significant predictor for recurrence (HR = 1.75, P = .007), death of disease (HR = 1.89, P = .003) and death (HR = 2.4, P < .001). CONCLUSIONS: Older age in women with endometrial cancer is associated with more adverse disease features, limited surgery and adjuvant treatment, and worse outcomes. On multivariable analysis, age remains an independent prognosticator in this population.

UVEITIS AFTER THE BNT162b2 mRNA VACCINATION AGAINST SARS-CoV-2 INFECTION: A Possible Association.

PURPOSE: To describe uveitis cases after the BNT162b2 mRNA SARS-CoV-2 vaccination. METHODS: This is a multicenter, retrospective study. Vaccine-related uveitis diagnosis was supported by the classification of the World Health Organization Adverse Drug Terminology and the Naranjo criteria. RESULTS: Twenty-one patients (23 eyes) with a mean age of 51.3 years (23-78 years) were included. Eight of the 21 patients had a known history of uveitis. The median time from previous to current attack was 1 year (0.5-15 years). There were 21 anterior uveitis cases, two with bilateral inflammation. Eight cases occurred after the first vaccination and 13 after the second vaccination. All but three presented as mild to moderate disease. Two patients developed multiple evanescent white dot syndrome after the second vaccination. The mean time from vaccination to uveitis onset was 7.5 ± 7.3 days (1-30 days). At final follow-up, complete resolution was achieved in all but two eyes, which showed significant improvement. One case of severe anterior uveitis developed vitritis and macular edema after the second vaccination, which completely resolved after an intravitreal dexamethasone injection. CONCLUSION: Uveitis may develop after the administration of the BNT162b2 mRNA vaccine. The most common complication was mild to moderate anterior uveitis, while multiple evanescent white dot syndrome can also occur less frequently.

Treatment Modality and Second Primary Tumors of the Head and Neck.

INTRODUCTION: Second primary tumors (SPTs) in head and neck cancer are thought to occur from premalignant lesions that are present at the time of the primary tumor diagnosis. The association of the modality used to treat the primary lesion with SPT occurrence is not clear. OBJECTIVE: The aim of the study was to assess the incidence of SPTs in patients with head and neck malignancies, according to treatment modality. METHODS: We conducted a retrospective cohort study. All patients who were treated at Soroka Medical Center between 2000 and 2013 for a head and neck squamous cell carcinoma were assessed. Data analysis included tumor site of the primary and second primary and treatment modality of the primary tumor. In addition, demographics as well as habits were recorded as well. RESULTS: Of the 184 patients included in the cohort, SPT developed in 31 patients (17%) with a median time to diagnosis of 4.3 years. Smoking was reported in 74% of those with SPT and 78% of those without. The most common site for SPT was the lungs, with 13 cases, 42% of the total SPTs. Among patients who developed an SPT, for 12 of those with an index tumor in the oral cavity or oro-hypopharynx, 8 (67%) developed an SPT in the same location; for 18 of those with an index tumor in the larynx, 11 (61%) developed a SPT in the lungs and bronchi (p = 0.001). On multivariate analysis, the treatment modality used was not found to be associated with the occurrence of SPTs and the radiotherapy showed no protective or harmful effect (HR 0.64 p = 0.24). CONCLUSION: Treatment modality used for head and neck cancer does not seem to be associated with the occurrence of SPTs.

[INTRAPARTUM ULTRASOUND - THE FUTURE IS HERE].

INTRODUCTION: This review aims to present the different applications and benefits of intrapartum ultrasound (IPUS) compared to the traditional digital vaginal examination. IPUS is non-invasive, does not cause pain or discomfort to the woman and may reduce the rate of ascending infections. In comparison to the vaginal exam, IPUS is more accurate in diagnosing fetal head position and station, is easy to acquire and has a faster learning curve. Applications of IPUS include: 1. Diagnosing the fetal head position either by suprapubic or trans-perineal ultrasound when the fetal head is low, which is more accurate than the digital vaginal exam; 2. Measuring cervical dilatation and effacement by trans-perineal ultrasound. This may be of more value especially in patients with ruptured membranes or patients who have difficulty with invasive examinations; 3. Assessing fetal head station and labor progress by measuring the head-perineal distance (HPD) and the angle of progression (AOP); 4. Estimating the pelvic size relative to the fetal head by measuring the pubic arch angle and fetal head circumference; 5. Predicting the mode of delivery before and during the labor process; 6. Prior to deciding the mode of delivery in a prolonged second stage of labor; 7. Providing a visual biofeedback to improve pushing efforts and mother-baby connection.

Blood-Brain Barrier Leakage: A New Biomarker in Transient Ischemic Attacks.

Background and Purpose- The diagnosis of transient ischemic attack is challenging. Evidence of acute ischemia on MRI diffusion-weighted imaging is highly variable and confirmed in only about one-third of patients. This study investigated the significance of blood-brain barrier dysfunction (BBBD) mapping in patients with transient neurological deficits, as a diagnostic and prognostic biomarker required for risk stratification and stroke prevention. Methods- We used dynamic contrast-enhanced MRI to quantitatively map BBBD in a prospective cohort study of 57 patients diagnosed with transient ischemic attack/minor stroke and 50 healthy controls. Results- Brain volume with BBBD was significantly higher in patients compared with controls ( P=0.002). BBBD localization corresponded with the clinical presentation in 41 patients (72%) and was more extensive in patients with acute infarct on diffusion-weighted imaging ( P=0.05). Patients who developed new stroke during follow-up had a significantly greater BBBD at the initial presentation ( P=0.03) with a risk ratio of 5.35 for recurrent stroke. Conclusions- This is the first description of the extent and localization of BBBD in patients with transient ischemic attack/minor stroke. We propose BBBD mapping as a valuable tool for detection of subtle brain ischemia and a promising predictive biomarker required for risk stratification and stroke prevention.

A Phase 2, International, Multicenter, Open-label Clinical Trial of Subcutaneous Tbo-Filgrastim in Pediatric Patients With Solid Tumors Undergoing Myelosuppressive Chemotherapy.

This phase 2, multicenter, open-label trial investigated the safety and tolerability of tbo-filgrastim in pediatric patients receiving myelosuppressive chemotherapy. In total, 50 patients 1 month to below 16 years of age with solid tumors without bone marrow involvement were stratified into 3 age groups (2 infants, 30 children, 18 adolescents) and prophylactically administered tbo-filgrastim 5 µg/kg body weight once daily subcutaneously. The administration started after the last chemotherapy treatment in week 1 of the first cycle and continued until the expected neutrophil nadir had passed, and the neutrophil count had recovered to 2.0×10/L. The primary endpoint was safety and tolerability of tbo-filgrastim; secondary endpoints included efficacy. The mean (SD) number of doses administered was 9.2 (2.83) in children and 7.3 (1.88) in adolescents. Serious treatment-emergent adverse events were reported in 24% of patients; the most common were febrile neutropenia (FN) (12%), anemia (8%), and thrombocytopenia (8%). Nine patients (18%) experienced mild treatment-related treatment-emergent adverse events; the most common were musculoskeletal and connective tissue disorders (8%). No deaths or withdrawals occurred. The incidence of severe neutropenia (SN) was 52% and the mean (SD) duration of SN was 1.8 (2.21) days; FN incidence was 26%. A daily dose of tbo-filgrastim 5 µg/kg body weight administered to pediatric patients demonstrated a safety profile consistent with the safety profile in adult patients. The incidence of FN was on the lower end of the range reported in the literature and the SN results provide supportive data on the efficacy of tbo-filgrastim in pediatric patients.

Effect of Menopausal Status on the Diagnosis of Endometrial Polyp.

OBJECTIVE: This study sought to compare the value of transvaginal ultrasonography (TVUS) and hysteroscopy in premenopausal and postmenopausal women in the diagnosis of endometrial polyp. METHODS: The records of 694 women with an ultrasonographic diagnosis of suspected endometrial polyp who underwent hysteroscopy were studied. Patients were divided into two groups according to menopausal status, and a comparison was made between two groups. RESULTS: There were 299 postmenopausal and 395 premenopausal women in the study. Hysteroscopy confirmed the ultrasonographic diagnosis of endometrial polyp in 212 (71%) and 212 (53%) patients in the postmenopausal and premenopausal groups, respectively (P = 0.001). In postmenopausal patients, 94% of the polyps observed by hysteroscopy were confirmed by histology, whereas in premenopausal patients, the percentage was 85% (P = 0.004). CONCLUSION: In premenopausal patients, the diagnostic value of TVUS and hysteroscopy is lower than in postmenopausal patients. The appropriate time for TVUS and hysteroscopy should be scheduled in premenopausal women, especially in women with abnormal uterine bleeding.

Endometrial Polyp Size and the Risk of Malignancy in Asymptomatic Postmenopausal Women.

OBJECTIVE: The appropriate management of endometrial polyps in asymptomatic postmenopausal patients remains controversial. The aim of the study was to evaluate the relationship between endometrial polyp size and malignancy risk among asymptomatic postmenopausal women. METHODS: This observational retrospective study investigated 472 postmenopausal asymptomatic women who underwent hysteroscopic polypectomy between 2010 and 2014 (Canadian Task Force Classification II-3). RESULTS: Of the 472 women, premalignant and malignant lesions were found in 11 (2.33%) cases; four (0.84%) had endometrial carcinoma, and seven (1.49%) had atypical endometrial hyperplasia. The incidence of premalignant or malignant lesions among various cut-offs of polyp size (10, 15, 20 mm) was not significantly different. CONCLUSION: In the current series no significant risk factor for malignancy was found among different cut-offs of polyp size.

Cervical Cancer with Intermediate Risk Factors: Is there a Role for Adjuvant Radiotherapy? A Systematic Review and a Meta-Analysis.

BACKGROUND: The yield of adjuvant radiotherapy in cervical cancer patients with intermediate risk factors is controversial. The objective of our meta-analysis was to shed light on this important issue. MATERIAL AND METHODS: Search was conducted in several databases. By independent screening of titles and abstracts, 2 investigators selected original researches examining the effect of adjuvant radiation treatment on overall survival and progression-free survival in cervical cancer patients with intermediate risk factors. RESULTS: Of the 5 articles included, a total of 591 patients with intermediate risk factors were encompassed. Statistical significance was noted in favor of radiation therapy in a subgroup of patients with 2 or more intermediate factors in terms of recurrence (OR 0.46 [95% CI 0.28-0.74, p = 0.001]) and overall survival (OR 1.86 [95% CI 1.03-3.36, p = 0.04]). After adding patients with one risk factor, radiation exerted a non-significant effect on recurrence rate, overall survival, disease-free survival, and 5-year cancer-specific survival, while increasing the rate of gastrointestinal side effects (2.4 vs. 0%, p = 0.0156). CONCLUSIONS: Adjuvant radiation therapy decreases the risk for recurrence and increases the overall survival in patients with 2 intermediate risk factors. These benefits were not shown after adding patients with one risk factor.

Protection of colorectal anastomosis with an intraluminal bypass device for patients undergoing an elective anterior resection: a pilot study.

BACKGROUND: Currently, the only clinically valid method to prevent morbidity and mortality related to colorectal anastomotic leaks is by construction of a protective ileostomy. Intraluminal bypass might also be a possible way to proctect the anastomosis. The aim of the present study was to evaluate the CG-100 intraluminal bypass device for the reduction of anastomosis-related morbidity and stoma creation in cases of rectal resection. METHODS: A prospective study was conducted on patients having sphincter-preserving rectal resection who were treated with the CG-100 device at Soroka University Medical Center, Beer Sheva, Israel between May 2015 and February 2017. The device was implanted during surgery and removed after 10 ± 1 days. All patients underwent a radiologic leak test with water-soluble contrast prior to removal of the device. Patients were followed for 30 days. Information about adverse events, anastomotic leaks, device usability and tolerance were collected. RESULTS: Forty-seven patients participated in the study. Most patients were operated on due to cancer 44 (93.6%). Four (9%) patients received a primary protective stoma on top of the CG-100 device as part of the learning curve of the surgical team and none required a stoma after device removal. Five (9%) serious adverse events were reported, but only 2 (4%) were classified as related to the device. One was a transient enterocutaneous fistula after removal of the device. The second was an asymptomatic radiologic leak in 1 (2.1%) patient which was treated by keeping the device in place and antibiotic treatment for another 10 days without creation of diverting ileostomy. CONCLUSIONS: CG-100 may provide a safe method for fecal diversion over a newly created anastomosis without the complications related to stoma creation and closure. A larger prospective randomized study in patients originally scheduled to receive diverting stoma is needed to confirm these findings.

[IDIOPATHIC RETINAL VASCULITIS - THE INTERPLAY BETWEEN A CHRONIC IDIOPATHIC OCULAR DISEASE, ITS THERAPY AND THE PATIENT].

INTRODUCTION: This is an article on a six year follow-up of a patient diagnosed with idiopathic retinal vasculitis. Her medical history, symptoms and findings are presented in detail, related to the diagnostic investigations and the resulting diagnosis. Patient follow-up was marked with repeated attempts to utilize steroid sparing strategies including antimetabolites such as Methotrexate and mycophenolate Mofetyl with only limited success. Biologic agent (anti TNF), Adalimumab, was also not successful. We discuss the difficulties experienced by the patient and her response to our inability to completely control her symptoms. On another level, we relate to our own difficulties to assess her response to therapy given her preserved vision on the one hand and her apparent uncontrolled retinal vascular leakage. The patient's ability to function in daily life reduces her willingness to endure therapy-related adverse events.

Is there a survival advantage in diagnosing endometrial cancer in asymptomatic postmenopausal patients? An Israeli Gynecology Oncology Group study.

BACKGROUND: Incidental ultrasonographic findings in asymptomatic postmenopausal women, such as thickened endometrium or polyps, often lead to invasive procedures and to the occasional diagnosis of endometrial cancer. Data supporting a survival advantage of endometrial cancer diagnosed prior to the onset of postmenopausal bleeding are lacking. OBJECTIVE: To compare the survival of asymptomatic and bleeding postmenopausal patients diagnosed with endometrial cancer. STUDY DESIGN: This was an Israeli Gynecology Oncology Group retrospective multicenter study of 1607 postmenopausal patients with endometrial cancer: 233 asymptomatic patients and 1374 presenting with postmenopausal bleeding. Clinical, pathological, and survival measures were compared. RESULTS: There was no significant difference between the asymptomatic and the postmenopausal bleeding groups in the proportion of patients in stage II-IV (23.5% vs 23.8%; P = .9) or in high-grade histology (41.0% vs 38.4%; P = .12). Among patients with stage-I tumors, asymptomatic patients had a greater proportion than postmenopausal bleeding patients of stage IA (82.1% vs 66.2%; P < .01) and a smaller proportion received adjuvant postoperative radiotherapy (30.5% vs 40.6%; P = .02). There was no difference between asymptomatic and postmenopausal bleeding patients in the 5-year recurrence-free survival (79.1% vs 79.4%; P = .85), disease-specific survival (83.2% vs 82.2%; P = .57), or overall survival (79.7% vs 76.8%; P = .37). CONCLUSION: Endometrial cancer diagnosed in asymptomatic postmenopausal women is not associated with higher survival rates. Operative hysteroscopy/curettage procedures in asymptomatic patients with ultrasonographically diagnosed endometrial polyps or thick endometrium are rarely indicated. It is reasonable to reserve these procedures for patients whose ultrasonographic findings demonstrate significant change over time.

[THE APPROACH TO INFECTIOUS UVEITIS IN CHILDREN].

INTRODUCTION: Uveitis is an inflammatory disease of the intraocular structures involving various parts of the eye. Delays in diagnosis or treatment can lead to severe and irreversible vision loss. There are many causes leading to the development of uveitis, including: infectious, inflammatory, autoimmune and idiopathic sources. Uveitis is rarer in children than in other age groups and its diagnosis is challenging and treatment is complex. This disease might present at later stages after vision damage is already present. Uveitis and decreased vision may be the presenting symptom and/or sign of various inflammatory diseases, which would become fully expressed many years later. This review is limited to uveitis of infectious origin in the pediatric population, with a focus on the most common pathogens, based on the main anatomical sections involved in this disease. Moreover, we will clarify existing diagnostic tools and treatment options relevant for each underlying cause.

Nato3 plays an integral role in dorsoventral patterning of the spinal cord by segregating floor plate/p3 fates via Nkx2.2 suppression and Foxa2 maintenance.

During embryogenesis, the dorsal roof plate and the ventral floor plate (FP) act as organizing centers to pattern the developing neural tube. Organizer-secreted morphogens provide signals that are interpreted via the graded expression of transcription factors. These factors establish a combinatorial code, which subsequently determines the fate of neuronal progenitors along the dorsoventral axis. To further separate the fates and promote distinct identities of the neural progenitors, mutual repression takes place among transcription factors expressed in progenitors situated along the dorsoventral axis. The molecular mechanisms acting in the developing spinal cord and underlying the segregation of the progenitor pool containing cells with a mixed FP/p3 fate into separate FP cells and V3 neurons are not fully understood. Using in vivo ectopic expression in chick, we found that Nato3 induces ectopic Foxa2-positive cells and indirectly downregulates Nkx2.2 expression. To examine the role of Nato3 in the FP, Foxa2-Nato3 signaling was blocked in Nato3 null mice and to a greater extent in Nato3 null/Foxa2 heterozygous bigenic mutants. Complementary to the findings obtained by gain of function in chick, the loss of function in mouse indicated that the segregation of the FP/p3 population into its derivatives was interrupted. Together, the data suggest that Nato3 is a novel determinant factor regulating the segregation of the FP and p3 identities, which is an essential step for establishing a definitive FP fate in the embryonic spinal cord.

[SENTINEL LYMPH NODES DISSECTION IN GYNECOLOGICAL MALIGNANCIES].

INTRODUCTION: During the last decade sentinel lymph nodes biopsy has become an essential part of primary surgical treatment in a number of malignancies including breast cancer, melanoma and head-and-neck malignancies. Dye or radioactive substances are injected at the primary tumor site, followed by pre-operative and intra-operative mapping. During surgery only positive lymph nodes are being dissected instead of a complete dissection of the lymphatic basin. The advantages of sentinel lymph nodes dissection are reducing the side effects of extensive lymph nodes dissection, while maintaining high detection rates and sensitivity in identifying cases with lymphatic tumor spread. In the past years, the use of sentinel lymph nodes biopsy has also been incorporated in the treatment of gynecological malignancies. In vulvar cancer, it has been shown that sentinel lymph nodes biopsy is correlated with the same survival and recurrence rates as full groin lymph nodes dissection, while substantially lowering complications and especially morbid lymphedema. Preliminary experience in cervical cancer and carcinoma of the endometrium also displays the feasibility and liability of this method. Yet, there are still several controversies regarding the optimal detection method, site of injection and its oncological safety. In this article we present a review of the current literature on this evolving field.