Mycobacterial HflX is a ribosome splitting factor that mediates antibiotic resistance.

Antibiotic resistance in bacteria is typically conferred by proteins that function as efflux pumps or enzymes that modify either the drug or the antibiotic target. Here we report an unusual mechanism of resistance to macrolide-lincosamide antibiotics mediated by mycobacterial HflX, a conserved ribosome-associated GTPase. We show that deletion of the hflX gene in the pathogenic Mycobacterium abscessus, as well as the nonpathogenic Mycobacterium smegmatis, results in hypersensitivity to the macrolide-lincosamide class of antibiotics. Importantly, the level of resistance provided by Mab_hflX is equivalent to that conferred by erm41, implying that hflX constitutes a significant resistance determinant in M. abscessus We demonstrate that mycobacterial HflX associates with the 50S ribosomal subunits in vivo and can dissociate purified 70S ribosomes in vitro, independent of GTP hydrolysis. The absence of HflX in a ΔMs_hflX strain also results in a significant accumulation of 70S ribosomes upon erythromycin exposure. Finally, a deletion of either the N-terminal or the C-terminal domain of HflX abrogates ribosome splitting and concomitantly abolishes the ability of mutant proteins to mediate antibiotic tolerance. Together, our results suggest a mechanism of macrolide-lincosamide resistance in which the mycobacterial HflX dissociates antibiotic-stalled ribosomes and rescues the bound mRNA. Given the widespread presence of hflX genes, we anticipate this as a generalized mechanism of macrolide resistance used by several bacteria.

Survival outcomes of women with grade 3 endometrioid endometrial cancer: the impact of adjuvant treatment strategies.

AIM: This multicenter investigation was performed to evaluate the adjuvant treatment options, prognostic factors, and patterns of recurrence in patients with grade 3 endometrioid endometrial cancer (G3-EEC). MATERIALS AND METHODS: The medical reports of patients undergoing at least total hysterectomy and salpingo-oophorectomy for G3-EEC between 1996 and 2018 at 11 gynecological oncology centers were analyzed. Optimal surgery was defined as removal of all disease except for residual nodules with a maximum diameter ≤ 1 cm, as determined at completion of the primary operation. Adequate systematic lymphadenectomy was defined as the removal of at least 15 pelvic and at least 5 paraaortic LNs. RESULTS: The study population consists of 465 women with G3-EEC. The 5-year disease-free survival (DFS) and overall survival (OS) rates of the entire cohort are 50.3% and 57.6%, respectively. Adequate systematic lymphadenectomy was achieved in 429 (92.2%) patients. Optimal surgery was achieved in 135 (75.0%) patients in advanced stage. Inadequate lymphadenectomy (DFS; HR 3.4, 95% CI 3.0-5.6; P = 0.016-OS; HR 3.2, 95% CI 1.6-6.5; P = 0.019) was independent prognostic factors for 5-year DFS and OS. CONCLUSION: Inadequate lymphadenectomy and LVSI were independent prognostic factors for worse DFS and OS in women with stage I-II G3-EEC. Adequate lymphadenectomy and optimal surgery were independent prognostic factors for better DFS and OS in women with stage III-IV G3-EEC.

Extracorporeal photopheresis and multimodality therapy in patients with T-cell cutaneous lymphomas: Real-life experience in Argentina.

BACKGROUND: Extracorporeal photopheresis (ECP) as a part of multimodality therapy, is one of the treatments for Sézary syndrome (SS) and advanced stage mycosis fungoides (MF). This study aims to describe cutaneous and peripheral blood responses of patients with MF and SS who received multimodality therapy. METHODS: In this cross-sectional retrospective study, patients with MF or SS who received ECP treatment in combination with at least one additional systemic treatment between 2011 and 2018 were included. ECP consisted of a two-session cycle every 2 to 4 weeks. Cutaneous and blood responses were evaluated with updated criteria. RESULTS: Twenty-eight patients (11 (39%) with MF and 17 (51%) with SS) were included. Their median age at diagnosis was 63 (57-67) years. The median number of treatments before ECP was 2 (1-3). Seven out of 11 patients with MF (63%) underwent an assessment of cutaneous response. Five patients (70%) presented a partial response; 1 (15%), stable disease, and 1 (15%) progressive disease. Thirteen of the 17 patients with SS (76%) underwent evaluation. One patient (8%) presented a complete cutaneous response; 6 (46%), a partial response; 5 (38%), stable disease; and 1 (8%), progressive disease. None of them relapsed during the study period in both groups. No ECP-related adverse effects occurred during the study. CONCLUSION: Most patients with SS and MF who underwent multimodality therapy with ECP had favorable cutaneous and blood response. It is safe to combine ECP with other treatments. Studies with large numbers of patients are necessary to assess the effects of ECP on patient survival.

Total retroperitoneal en bloc resection of multivisceral-peritoneal packet (TROMP operation): a novel surgical technique for advanced ovarian cancer.

BACKGROUND: A Total Retroperitoneal en bloc resection Of Multivisceral-Peritoneal packet (TROMP operation) is a no-touch isolation technique in a retroperitoneal space to resect the parietal peritoneum and the affected organs in advanced ovarian cancer. The study prescribed and analysed the results of this novel technique for primary cytoreductive surgery. METHODS: The study included 208 patients operated between January 2015 and December 2017 in Charité, Berlin. The TROMP operation was performed in 58 patients, whereas the other 150 patients were operated with the conventional cytoreductive method. RESULTS: The complete tumor resection rate accounts for 87.9% in TROMP group and 61.3% in the conventional surgery group. (p=0.001). This difference was even stronger in the sub-group of very advanced stages (T3c+T4) (85.1% of TROMP group and in only 53.1% in the conventional surgery group, p=0.001). The duration of the primary cytoreductive surgery was about 33 minutes shorter in TROMP group (median: 335 minutes vs 368 minutes; TROMP vs conventional, respectively) in spite of the fact that the most advanced cytoreductive procedures were performed statically significant more in TROMP operation arm in comparison with the conventional surgery arm. There was no statistically significant difference between the groups regarding the postoperative complication, blood loss or the length of stay in intensive care unit. CONCLUSION: Total retroperitoneal en bloc resection of multivisceral-peritoneal packet (TROMP operation) is a feasible and very effective technique of surgical therapy in advanced ovarian cancer. This technique increased the complete tumor resection rate to 87.9% without increasing the blood loss, postoperative complications or the duration of surgery. A prospective randomized study is advised to validate these results.

Assessing HPV vaccination perceptions with online social media in Italy.

OBJECTIVE: Because of the widespread availability of the internet and social media, people often collect and disseminate news online making it important to understand the underlying mechanisms to steer promotional strategies in healthcare. The aim of this study is to analyze perceptions regarding the human papillomavirus (HPV) vaccine in Italy. METHODS: From August 2015 to July 2016, articles, news, posts, and tweets were collected from social networks, posts on forums, blogs, and pictures about HPV. Using other keywords and specific semantic rules, we selected conversations presenting the negative or positive perceptions of HPV. We divided them into subgroups depending on the website, publication date, authors, main theme, and transmission modality. RESULTS: Most conversations occurred on social networks. Of all the conversations regarding HPV, more than 50% were about vaccination. With regard to conversations exclusively on the HPV vaccine, 47%, 32%, and 21% were positive, negative and neutral, respectively. Only 9% of the conversations mentioned the vaccine trade name and, in these conversations, perception was almost always negative. We observed many peaks in positive conversation trends compared with negative trends. The peaks were related to the web dissemination of particular news regarding HPV vaccination. CONCLUSIONS: In this study we have shown how mass media influences the diffusion of both negative and positive perceptions about HPV vaccines and suggest better ways to inform people about the importance of HPV vaccination.

Anterior colporrhaphy plus inside-out tension-free vaginal tape for associated stress urinary incontinence and cystocele: 10-year follow up results.

AIMS: We report the success rate and complications rate of combined ultralateral anterior Colporrhaphy plus Tension-free Vaginal Tape (TVT-O) in a long-term (10 year) follow-up prospective survey. METHODS: Patients previously treated for associated stress urinary incontinence (SUI) and cystocele were subjected to annual follow-up for 10 year with a complete urogynecologic evaluation. Furthermore, an urodynamic assessment and a quality of life questionnaire (ICIQ-UI SF) were recorded at the 5th and 10th year of follow up. RESULTS: Fifty patients treated between June 2004 and May 2006 were included in the analysis. Five patients did not return to 5-yr follow-up: two patients developed a median tape erosion and three patients withdraw. At 10-yr follow-up two more patients withdraw for a total of seven patients lost to follow-up. After 10 years patients objectively cured from cystocele were 41 (95%) while patients objectively cured from SUI were 39 (91%). At 10th year follow-up 38 patients (89%) result cured from both SUI and cystocele, 3 (7%) patients result cured only from prolapse, 1 (2%) patient only from SUI, and 1 (2%) patient result objectively failed for both SUI and cystocele. The ICIQ-UI SF scores at 10th year follow-up was 6.2 ± 3.7. The late complication rate at 10th year follow-up was 32% (OAB symptoms 20%; Mixed incontinence 2%; Bladder outlet obstruction 0%; Dyspareunia 6%; Chronic pelvic pain 0%; Vaginal tape erosion 4%; Detrusor hyperactivity 0%). CONCLUSIONS: The combined procedures shown proved to be an effective and safe procedure to treat concomitant SUI and cystocele.

Placenta accreta and balloon catheterization: the experience of a single center and an update of latest evidence of literature.

PURPOSE: We studied the efficacy of using pre-cesarean delivery (CD) temporary occlusion of internal iliac arteries with balloon catheters in case of placenta previa-accreta in terms of maternal and neonatal outcomes and to test accuracy of ultrasound (US) and magnetic resonance imaging (MRI) for prenatal diagnosis. METHODS: From March 2014 to January 2018, women with an US and/or MRI diagnosis of placenta previa-accreta and a planned delivery were enrolled and divided into two groups: balloon catheterization group (women treated with preoperative catheters and CD) and control group (women candidates to elective CD). RESULTS: 37 patients were enrolled: 16 in balloon catheterization group and 21 in control group. Significant differences were detected in estimated blood loss. Prophylactic balloon catheterization could reduce intraoperative red blood cell transfusion. The incidence of hysterectomy was lower in balloon group. No statistical difference was found for neonatal outcomes. Both US and MRI have showed to be useful and complementary to diagnose placenta previa-accreta. CONCLUSIONS: Temporal, perioperative, and prophylactic positioning of balloon vascular catheters is an effective method for managing severe hemorrhage caused by placenta previa-accreta as it reduced intraoperative blood loss, lessened perioperative hemostatic measures and intraoperative red cell transfusions, and reduced hysterectomies.

Population dynamics of Siderastrea stellata Verrill, 1868 from Rocas Atoll, RN: implications for predicted climate change impacts at the only South Atlantic atoll.

Coral reefs are one of the most vulnerable ecosystems to ocean warming and acidification, and it is important to determine the role of reef building species in this environment in order to obtain insight into their susceptibility to expected impacts of global changes. Aspects of the life history of a coral population, such as reproduction, growth and size-frequency can contribute to the production of models that are used to estimate impacts and potential recovery of the population, acting as a powerful tool for the conservation and management of those ecosystems. Here, we present the first evidence of Siderastrea stellata planulation, its early growth, population size-frequency distribution and growth rate of adult colonies in Rocas Atoll. Our results, together with the environmental protection policies and the absence of anthropogenic pressures, suggest that S. stellata population may have a good potential in the maintenance and recovery in the atoll. However, our results also indicate an impact on corals' recruitment, probably as a consequence of the positive temperature anomaly that occurred in 2010. Thus, despite the pristine status of Rocas Atoll, the preservation of its coral community seems to be threatened by current global changes, such as more frequent thermal stress events.

The role of HE4 in endometrial cancer recurrence: how to choose the optimal follow-up program.

The aim of this study was to evaluate for the first time in the literature the role of HE4, at primary diagnosis, compared to CA125 as an indicator of endometrial cancer (EC) recurrence. Our study is a retrospective analysis of 252 EC patients treated, between January 2009 and July 2013, at the Division of Gynaecologic Oncology of Campus Bio-Medico University of Rome. Thirty-seven patients experienced recurrence. Median follow-up was 38 months. HE4 and CA125 levels were analyzed at primary diagnosis, during follow-up and either after histological or radiological confirmation of recurrent disease or at last registered visit, when patients returned to our Department with no evidence of recurrent disease. A statistically significant difference was observed between HE4 values at primary diagnosis and at recurrence, respectively, comparing recurrent and non-recurrent patients (p < 0.05), while CA125 values resulted not statistically significant (p = 0.08) at each time point. Considering the poor specificity of HE4 at threshold of 70 pmol/L at primary diagnosis, in our cohort of patients, we found out that HE4 cut-off of 201.3 pmol/L is able to correctly classify patients at high or low risk of EC recurrence, with a sensitivity of 80 % and a specificity of 91 % (PPV = 90.3 % and NPV = 90.8 %). In particular, HE4 performance improves in cases of endometrioid histotype. HE4 levels at primary diagnosis correlate with an increased risk of EC recurrence, particularly in cases of endometrioid histotype, and they may help to recognize patients who may need a more intensive follow-up.

A Predictive Score for Secondary Cytoreductive Surgery in Recurrent Ovarian Cancer (SeC-Score): A Single-Centre, Controlled Study for Preoperative Patient Selection.

BACKGROUND: The standard treatments of patients with platinum-sensitive recurrent ovarian cancer (ROC) remains poorly defined. Chemotherapy (CT) and secondary cytoreductive surgery (SCS) represent both valid options, even if several studies demonstrated a greater survival benefit, with survival rates up to 62 months, for platinum-sensitive patients undergoing complete SCS. The purpose of the present study was to develop a predictive model, named SeC-Score (SeC-s), to assess the risk of optimal SCS, including, for the first time in literature, HE4. METHODS: All patients affected by suspicious ROC at radiologic imaging, referred to the Department of Gynecology of Campus Bio-medico of Rome, were prospectively included in the study. The preoperative variables considered in our predictive model were: age, residual tumour (RT) at primary cytoreduction (0 vs. >0 cm), preoperative CA125 and HE4, and ascites at recurrence. After exploratory laparotomy, patients were submitted to secondary SCS (Group A) or addressed to CT (Group B). RESULTS: A total of 135 patients with ROC were considered for the analysis. Preoperative CA125, HE4, ascites, and RT at first surgery were found statistically significant and included into a multivariate logistic regression model to determine the risk to not optimal SCS. In the overall cohort of patients, SeC-s reported sensitivity and specificity of 82 and 83 %, respectively (PPV = 0.79, NPV = 0.81). CONCLUSIONS: Our data support the use of SeC-s to preoperative triage patients suitable of optimal SCS, even if external validation is needed.

Quality of Life in Platinum-Sensitive Recurrent Ovarian Cancer: Chemotherapy Versus Surgery Plus Chemotherapy.

PURPOSE: This study was designed to compare quality of life in a sample of Italian patients affected by platinum-sensitive recurrent ovarian cancer and submitted to chemotherapy alone or secondary cytoreductive surgery plus chemotherapy through validated questionnaires. METHODS: From January 2007 to December 2012, consecutive patients with suspicious recurrence of ovarian cancer, referred to the Division of Gynecologic Oncology at the University Campus Bio-Medico of Rome, were assessed for this prospective, case-control study. After a diagnostic laparoscopy, surgical resectable patients were enrolled in group A (surgery plus chemotherapy). Patients not suitable for optimal debulking surgery and all patients who refused surgery were enrolled in group B (chemotherapy alone). At beginning of treatment, after the third and sixth cycle of chemotherapy, all eligible patients were asked to fill in QLQ-C30 (version 3.0) and EORTC QLQ-OV28 questionnaires. RESULTS: Group A included 38 patients and underwent SCS followed by chemotherapy; group B included 16 patients that were submitted to chemotherapy alone. Quality-of-life scores of both questionnaires were comparable between groups, with the exception of constipation and pain, which resulted significantly worsened in Group A at 3 months. This difference was no longer present at 6 months. Median overall survival was 72 % for Group A and 56 % in Group B at median follow-up of 35 months for Group A and 32 months for Group B. CONCLUSIONS: Both surgery followed by chemotherapy and chemotherapy alone seem to have a negligible impact on QOL. SCS plus chemotherapy seems to be an effective and tolerable therapeutic option in platinum-sensitive recurrences.

Utility of tumor marker HE4 as prognostic factor in endometrial cancer: a single-center controlled study.

This study aims to investigate the correlation between preoperative human epididymis protein 4 (HE4) levels, endometrial cancer (EC) staging, and ideal cutoff for stage prediction. All EC patients, treated within January 2009 and February 2014 at the Division of Gynaecologic Oncology of the University Campus Bio-Medico of Rome, were considered for the study. For the first part of the study, we consider an HE4 cutoff of 70 pmol/L. Histotypes (endometrioid versus non-endometrioid), grading (G1, G2, G3), and stage were correlated with HE4 levels. In the second part of the study, the logistic regression was performed in stepwise mood to identify the ideal HE4 cutoff for stage prediction. Two hundred thirty-two patients with surgically staged EC and preoperative HE4 dosage were included in the study. We found that higher HE4 levels correlate with undifferentiated grading (p < 0.05). Moreover, we found that 42, 77, 90, 93 and 100 % of patients classified as International Federation of Gynecology and Obstetrics (FIGO) stage IA, IB, II, III, and IV, respectively, presented HE4 levels above the standard cutoff of 70 pmol/L. Based on receiver operating characteristic (ROC) curves, we found the ideal HE4 cutoff as follows: 61.3 pmol/L for FIGO stage IA (sensitivity = 82.3 % and specificity = 96 %), 89.2 pmol/L for FIGO stage IB (sensitivity = 83.3 % and specificity = 96 %), 104.3 pmol/L for FIGO stage II (sensitivity = 80.9 % and specificity = 98.6 %), 152.6 pmol/L for FIGO stage III (sensitivity = 92.5 % and specificity = 98.6 %), and 203.8 pmol/L for FIGO stage IV (sensitivity = 81.8 % and specificity = 99.3 %). Our results suggest a potential role of HE4 in EC stage prediction.

Economic Impact Among Family Caregivers of Patients With Advanced Ovarian Cancer.

OBJECTIVES: The life of a family caregiver changes in many ways when cancer is diagnosed. Changes regard also financial costs. To the authors' knowledge, little work has been done to estimate the costs associated with caregiving for cancer patients. The aim of the present study is to evaluate for the first time in literature the economic changes among family caregivers of advanced ovarian cancer during the first-line treatment in an Italian survey. METHODS: Between January 2009 and June 2014, the primary family caregivers of patients with advanced ovarian cancer (N = 172) were recruited from to the Division of Gynecologic Oncology of the University Campus Bio-Medico of Rome within 4 weeks of the patient's new diagnosis. Caregivers reported demographic, medical information, and economic cost, such as traveling to and from medical appointments, waiting with patients for appointments, missing work, and attending to patients who are hospitalized. RESULTS: Between January 2009 and June 2014, 172 primary family caregivers of patients with advanced ovarian cancer were enrolled in the study. The mean age of the study cohort was 54.01 years. They reported 3% of missing workdays. The mean cost for all caregivers was &OV0556;1,888,732 per year. Therefore, the mean cost for each caregiver was &OV0556;10,981 annually. CONCLUSIONS: This economic analysis of caregiving in patients with advanced ovarian cancer reports the significant burden that cancer treatment places on both families and society. These findings underscore the importance, when appropriate, of including valid estimates of the cost of informal caregiving when evaluating the cost-effectiveness of cancer treatments.

Chemotherapy as Adjuvant Treatment for Intermediate-High Risk Early-Stage Endometrial Cancer: A Pilot Study.

OBJECTIVE: This study aimed to assess primarily the role of chemotherapy as adjuvant treatment for International Federation of Gynecology and Obstetrics (FIGO) stage IA G3, IB G2-G3, and II endometrial cancer (EC) in terms of disease-free interval and overall survival, and secondarily, the rate of local and distant recurrence. METHODS: The present prospective pilot study includes 68 patients with surgical staged EC who referred between 2007 and 2011 to the Division of Gynecologic Oncology at the University Campus Bio-Medico of Rome. All enrolled patients received adjuvant chemotherapy every 3 weeks according to the scheme carboplatin, dosed at an area under the curve of 6, and paclitaxel 175 mg/mq given every 3 weeks for at least 3 cycles. RESULTS: The median number of chemotherapy cycles was 6 (range, 3-6 cycles). Chemotherapy was well tolerated. The 3-year overall survival was 92.8% and 91.6% for stages I and II, respectively. The 3-year disease-free interval was 91.8% and 83.3% for stages I and II, respectively. Of 68 patients, 7 (10.3%) relapsed: 5 patients with a FIGO stage I and 2 patients with FIGO stage II EC. CONCLUSIONS: Platinum-based chemotherapy is feasible and safe and it could be used in adjuvant setting for early-stage ECs. Although its effectiveness is comparable to radiotherapy, chemotherapy represents an excellent treatment option due to its systemic action. Further randomized studies will be needed to confirm our promising data.

Influence of pneumoperitoneum pressure on surgical field during robotic and laparoscopic surgery: a comparative study.

PURPOSE: Studies on the influence of CO2 pneumoperitoneum on the abdominal cavity during robotic procedures are lacking. This is the first study to evaluate surgical field modifications related to CO2 pressure, during laparoscopic and robotic surgery. METHODS: Consecutive patients scheduled for laparoscopic or robotic hysterectomy were enrolled in the study. To evaluate the level of operative field visualization, a dedicated form has been designed based on the evaluation of four different areas: Douglas space, vesico-uterine fold and, bilaterally, the broad ligament. During the initial inspection, an assistant randomly set the CO2 pressure at 15, 10 and 5 mmHg, and the surgeon, not aware of the CO2 values, was asked to give an evaluation of the four areas for each set pressure. RESULTS: In laparoscopic group, CO2 pressure significantly influenced the surgical field visualization in all four areas analyzed. The surgeon had a good visualization only at 15 mmHg CO2 pressure; visualization decreased with a statistically significant difference from 15 to 5, 15-10 and 10-5 mmHg. In robotic group, influence of CO2 pressure on surgical areas visualization was not straightforward; operative field visualization remained stable at any pressure value with no significant difference. CONCLUSIONS: Pneumoperitoneum pressure significantly affects the visualization of the abdomino-pelvic cavity in laparoscopic procedures. Otherwise, CO2 pressure does not affect the visualization of surgical field during robotic surgery. These findings are particularly significant especially at low CO2 pressure with potential implications on peritoneal environment and the subsequent post-operative patient recovery.

A critical review on HE4 performance in endometrial cancer: where are we now?

To date, no good marker for endometrial cancer (EC) that may be routinely used in clinical practice for diagnosis, prognosis and monitoring is available; besides the use of tumour markers is not recommended by international guidelines. However, during the last years, an increasing interest in literature has been growing on human epididymis protein 4 (HE4) that demonstrated to be a useful clinical marker with high sensitivity and specificity even at early stage. However, published studies differ for some variables such as HE4 cut-off and sample size. Therefore, we assess this comprehensive review to gather all the evidence reported in literature on HE4 potential value in diagnosis, prognosis, and recurrence of EC. A systematic literature search was performed using PubMed/PubMed Central/MEDLINE predefined keywords from January 1952 to June 2013. We divided all the relevant studies into three different clinical issues: "Diagnosis", "Prognosis" and "Disease monitoring". The analysis of published data suggests that HE4 is the most accurate and sensitive EC marker identified to date. In particular, this new marker seems to have a good performance in diagnosis. The best cut-off of HE4 in diagnosis ranges between 50 and 70 pmol/L, resulting at least in 78.8 % of sensitivity and 100 % of specificity in all stages. Another important aspect to consider is HE4 capacity in predicting the stage of disease and myometrial involvement, which can help scheduling the appropriate timing of imaging and surgery in a more individualised fashion and as indicator of patients prognosis.

Can HE4 predict platinum response during first-line chemotherapy in ovarian cancer?

Actually, in literature there are not valid tools able to predict the chemotherapy response during first-line ovarian cancer treatment. CA125 and human epididymis protein 4 (HE4) levels of consecutive single-institution patients with epithelial ovarian cancer (EOC) were measured during first-line chemotherapy and until 6 months follow-up. First, patients were divided into two groups according to a temporal criterion: patients treated during 2009 (group A: training group) and patients treated during 2010 (group B: verification group). At sixth months follow-up, patients were sub-classified, within both groups, as platinum resistant or platinum sensitive/intermediate, according to Response Evaluation Criteria in Solid Tumors criteria, and the serum marker courses were further analyzed in each subgroup. Moreover, we performed a logistic regression analysis to choose CA125 and HE4 levels that are best fitted to predict chemoresponse. A total of 76 patients were divided into two groups: group A (n = 42) and group B (n = 34). After 6 months of follow-up, 40 patients were classified as platinum sensitive/intermediate and 36 as platinum resistant. At third chemotherapy cycle, in platinum-resistant patients, HE4 levels were >70 pmol/L in 36 of 36 cases, although in platinum-sensitive/intermediate patients, HE4 levels were >70 pmol/L only in six of 40 cases (sensitivity 100 %, specificity 85 %). Moreover, HE4 reduction of almost 47 % at third chemotherapy cycle reached the sensitivity of 83 % with a specificity of 87 % (positive predictive value = 0.86, negative predictive value = 0.85) in predicting chemoresponse. On the contrary, CA125 values during chemotherapy did not result statistically significant in predicting platinum response. Our findings suggest that HE4 values during first-line chemotherapy could predict chemotherapy response in EOC patients.

Recurrent Headache With Diplopia: A Common Presentation of an Uncommon Entity.

Recurrent painful ophthalmoplegic neuropathy (RPON) is a rare headache syndrome, the diagnosis of which can be daunting to those who are not familiar with it. It presents characteristically with recurrent ocular motor weakness and ipsilateral head pain without an underlying etiology and often has unique imaging findings. Even after the successful diagnosis of this entity, there are no published management guidelines. Here, we present the case of a 31-year-old man whom we diagnosed with RPON following two episodes of unilateral headache with ophthalmoplegia over a three-month period and treated successfully with high-dose steroids on both occasions. We highlight the lack of prior migraine history and seeming antecedent viral infection as potential supporting evidence that this condition has a unique pathophysiology different from migraine. We also highlight his dramatic and reproducible response to steroids as additional evidence that steroids are good acute treatment options for this condition. Finally, as our patient lacked the expected cranial nerve imaging abnormalities on head MRI, we suggest that cranial nerve thickening and/or enhancement on MR imaging is not a sine qua non for this diagnosis, contrary to the opinion of some experts.