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(1) Background: to retrospectively evaluate safety and efficacy of combined microwave ablation (MWA) and bilateral expandable titanium SpineJack (SJ) implants followed by vertebroplasty (VP) for the treatment of painful thoracolumbar pathological vertebral compression fracture. (2) Methods: from July 2017 to October 2022, twenty-eight patients (13 women and 15 men; mean age 68 ± 11 years) with a history of primary neoplasm and thirty-six painful vertebral metastases with vertebral compression fracture underwent combined MWA and bilateral expandable titanium SpineJack implants with vertebroplasty. We analyzed safety through complications rate, and efficacy through vertebral height restoration and pain decrease, evaluated using a visual analogue scale (VAS), and Functional Mobility Scale (FMS), and local tumor control. Contrast-enhanced CT scans were performed at 1, 3, and 6 months and a contrast-enhanced spine MRI at 6 months after the procedure. (3) Results: Technical success rate was 100%. No procedure-related major complications or death occurred. Vertebral height restoration was observed in 22 levels (58%), with a mean anterior height restoration of 2.6 mm ± 0.6 and a mean middle height restoration of 4.4 mm ± 0.6 (p < 0.001). Mean VAS score of pain evaluation on the day before treatment was 6.3 ± 1.5 (range 4–9). At the 6-month evaluation, the median VAS score for pain was 0.4 ± 0.6 (range 0–2) with a mean reduction of 93.65% (6.8 ± 0.7 vs. 0.4 ± 0.6; p < 0.000) compared with baseline evaluation. Contrast-enhanced CT scans were performed at 1, 3, and 6 months and a contrast-enhanced spine MRI was performed at 6 months after the procedure, showing no local recurrence, implant displacement, or new fractures in the treated site. (4) Conclusions: combined microwave ablation and bilateral expandable titanium SpineJack implants with vertebroplasty is a safe and effective procedure for the treatment of pathological compressive vertebral fractures. The vertebral stabilization achieved early and persistent pain relief, increasing patient mobility, improving recovery of walking capacity, and providing local tumor control.

Consalvo Mattia,1,2 Livio Luongo,3,4 Massimo Innamorato,5 Luca Melis,6 Michele Sofia,7 Lucia Zappi,8 Filomena Puntillo9,10 1Department of Medical and Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine, “Sapienza” University of Rome, Rome, Italy; 2Anesthesia, Intensive Care and Pain Unit, ICOT-Polo Pontino, Latina, Italy; 3Department of Experimental Medicine, Division of Pharmacology, University of Campania “L. Vanvitelli”, Naples, Italy; 4NEUROMED, Pozzilli, Italy; 5Pain Therapy Unit, AUSL Romagna, S.M.Croci Hospital Ravenna, Ravenna, Italy; 6Poliste, Cagliari, Italy; 7Department of Palliative Care and Pain Therapy, ASST Rodhense, Garbagnate Milanese, Itlay; 8UOC Antalgic Therapy, Emergency and Acceptance Department, San Martino Polyclinic Hospital, Genoa, Italy; 9Department of Interdisciplinary Medicine, “Aldo Moro” University of Bari, Bari, 70124, Italy; 10Anesthesia, Intensive Care and Pain Unit, Policlinico Hospital of Bari, Bari, 70124, ItalyCorrespondence: Consalvo MattiaDepartment of Medical and Surgical Science, University Sapienza, Corso della Repubblica, 79, Latina, 04100, ItalyTel +39 0773 6511Email consalvo.mattia@uniroma1.itPurpose: The aim of the present work was to evaluate the knowledge and prescriptive habits of clinicians involved in the management of chronic non cancer pain (CNCP), with a special focus on the use of opioids.Methods: A Delphi method was used. A Board of specialists elaborated and discussed a series of statements, based on available literature and personal clinical expertise, about particularly controversial topics on pain pathophysiology and treatment. A Panel of experts in the field of pain management, selected by the Board, was invited to vote the proposed statements, indicating the level of agreement on a 5-point Likert scale (1: strongly disagree; 2: disagree; 3: partially agree; 4: agree; 5: strongly agree). The threshold for consensus was set at minimum 66.6% of the number of respondents with a level of agreement ≥ 4 (Agree or Strongly agree).Results: The Board included 5 pain therapists, 1 pharmacologist and 1 methodology expert and drew up a total of 36 statements (for a total of 40 requested answers)”. A total of 100 clinicians were included in the Expert Panel. Respondents were 89 (89%). Consensus was achieved for 32 out of 40 answers. Most of the lack of consensus was recorded for statements regarding opioids use, and resulted from a low level of agreement (3 on the Likert scale), suggesting a neutral position deriving from a lack of knowledge rather than a strong contrary opinion.Conclusion: Most of the proposed items reached consensus, suggesting a generally homogeneous approach to CNCP management. However, the lack of consensus recorded for several items regarding opioid use confirms the need to fill important gaps in the knowledge of available agents. A clear explanation of the peculiar pharmacological properties of drugs associated with potential clinical advantages (such as buprenorphine) will help optimize pain treatment in both primary care and hospital settings and improving pain control in CNCP patients.Keywords: pain, chronic, non-oncological, strong opioids, buprenorphine, Delphi survey

BACKGROUND Giant ovarian cysts (≥ 15 cm in diameter) are rare. The size limit of cysts and the methodology for a safe and successful minimally invasive surgery has not been established. Here we report a case of a large 10-kg multi-locular ovarian mass, which was successfully laparoscopically removed: Our aim was to innovate the surgical practice in this field by providing a safe, effective, and minimally invasive management method for such complex and rare cases. CASE SUMMARY A 49-year-old nulliparous woman presented with abdominal distension, lasting from six Mo prior to admission; she reported worsening abdominal pain, abdominal swelling, and mild dyspnea. Imaging showed a presumed benign multi-locular (> 10 locules) left ovarian cyst that measured about 30 cm in diameter. Based on the IOTA-ADNEX model the mass had a 27.5% risk of being a borderline or malignant tumor. The patient was successfully treated via a direct laparoscopic approach with salpingo-oophorectomy, followed by the external drainage of the cyst. Tumor spillage was successfully avoided during this procedure. The final volume of the drained mucinous content was 8950 L; the cyst wall, extracted through the minilaparotomy, weighed about 1200 g. The pathologic gross examination revealed a 24 cm × 15 cm × 10 cm mass; the histologic examination diagnosed a mucinous cystoadenoma. To our knowledge, this is the first case of a giant multi-locular ovarian cyst treated with a direct laparoscopy with salpingo-oophorectomy followed by external decompression. CONCLUSION Choosing the appropriate technique and surgeon skill are necessary for a safe and effective minimally-invasive approach of unique cases involving giant ovarian cysts.

The identification of prognostic and predictive markers is crucial for choosing the most appropriate management method for ovarian cancer patients. We aimed to assess the prognostic role of tumor-associated macrophage (TAM) polarization in advanced ovarian cancer patients. We carried out a prospective observational study that included 140 consecutive patients with advanced-stage high-grade serous ovarian cancer as well as patients with other histotypes of ovarian cancer and patients with ovarian metastasis from other sites between June 2013 and December 2018. Patients were enrolled at the time of laparoscopic surgery before receiving any antineoplastic treatment. We found that patients with high-grade serous papillary ovarian cancers had a prevalence of M1 TAMs, a higher M1/M2 ratio, and a longer overall survival (OS) and progression-free survival (PFS) than other patients. Regression analysis confirmed that there was a significant positive association between the M1/M2 ratio and an improved OS, PFS and platinum-free interval (PFI), both in the entire population and in patients stratified according to tumor type and initial surgery. Kaplan-Meier analysis was performed after the patients were divided into 2 groups according to the median M1/M2 ratio and revealed that patients with a high M1/M2 ratio had a higher OS, PFS and PFI than those with a low M1/M2 ratio. In conclusion, the prognostic and predictive role of TAM polarization in the tumor microenvironment could be of great clinical relevance and may allow the early identification of patients who are likely to respond to therapy. Further studies in a larger prospective sample are warranted.

Bartholin gland adenocarcinoma (BGA) is extremely rare and is characterized by high rates of lymph-node recurrence and distant metastases. No effective palliative treatments are available for metastatic BGA; therefore, advanced BGA remains a challenge for gynecologic oncologists. Considering the rarity of this disease and the lack of a standardized approach, the present study aims to discuss the available literature on current therapies for BGA and to describe an emblematic case treated with a novel tailored approach. A postmenopausal woman with advanced BGA was referred to our department for an adequate evaluation, staging and treatment. Notably, we used PET/CT as a fundamental imaging technique for staging and follow-up. The patient underwent primary surgery followed by standard chemotherapy and pelvic radiotherapy. Three months later, she relapsed, with the appearance of multiple metastatic sites. Considering the evident chemoresistance to standard chemotherapy and the absence of valid therapeutic alternatives for this rare cancer, she was treated with a combination of repeated minimally invasive surgical procedures for all the resectable metastatic lesions and innovative approaches comprising, firstly, chemoimmunotherapy with Nivolumab combined with metronomic vinorelbine, which resulted in a clinical response for approximately 7 months. Upon disease progression, we used a targeted systemic approach based on the whole genomic profile of the primary tumor, which showed PTEN loss, which is predictive of a benefit from an mTOR inhibitor, and a CCND1 amplification, which predicts sensitivity to CDK4/6 inhibitors. Therefore, she received Everolimus, resulting in a significant metabolic response that lasted 12 months. Thereafter, upon further progression of the disease, the patient started Palbociclib treatment, which is currently ongoing, with evidence of a metabolic response. The patient has survived for 54 months from diagnosis, with a good performance status. In conclusion, the present paper confirms the lack of efficacy of conventional therapeutic regimens in the context of advanced, recurrent or metastatic adenocarcinomas of the Bartholin gland. The case report shows how a personalized multidisciplinary approach based on repeated minimally invasive surgery and tailored anticancer treatment based on whole-genome sequencing analysis could be effective and associated with prolonged survival in this rare gynecological cancer. ispartof: DIAGNOSTICS vol:11 issue:11 ispartof: location:Switzerland status: published

Aims: The purpose of this study was to assess the effectiveness of a navigational radiofrequency ablation device with concurrent vertebral augmentation in the treatment of posterior vertebral body metastatic lesions, which are technically difficult to access. Primary outcomes of the study were evaluation of pain palliation and radiologic assessment of local tumor control. Materials and Methods: Thirty-five patients with 41 vertebral spinal metastases involving the posterior vertebral body underwent computed tomography-guided percutaneous targeted radiofrequency ablation, with a navigational radiofrequency ablation device, associated with vertebral augmentation. Twenty-one patients (60%) had 1 or 2 metastatic lesions (Group A) and fourteen (40%) patients had multiple (&gt, 2) vertebral lesions (Group B). Changes in pain severity were evaluated by visual analog scale (VAS). Metastatic lesions were evaluated in terms of radiological local control. Results: The procedure was technically successful in all the treated vertebrae. Among the symptomatic patients, the mean VAS score dropped from 5.7 (95% CI 4.9–6.5) before tRFA and to 0.9 (95% CI 0.4–1.3) after tRFA (p &lt, 0.001). The mean decrease in VAS score between baseline and one week follow up was 4.8 (95% CI 4.2–5.4). VAS decrease over time between one week and one year following radiofrequency ablation was similar, suggesting that pain relief was immediate and durable. Neither patients with 1–2 vertebral metastases, nor those with multiple lesions, showed radiological signs of local progression or recurrence of the tumor in the index vertebrae during a median follow up of 19 months (4–46 months) and 10 months (4–37 months), respectively. Conclusion: Treatment of spinal metastases with a navigational radiofrequency ablation device and vertebral augmentation can be used to obtain local tumor control with immediate and durable pain relief, providing effective treatment in the multimodality management of difficult-to-reach spinal metastases.

Generative models estimate the underlying distribution of a dataset to generate realistic samples according to that distribution. In this paper, we present the first membership inference attacks against generative models: given a data point, the adversary determines whether or not it was used to train the model. Our attacks leverage Generative Adversarial Networks (GANs), which combine a discriminative and a generative model, to detect overfitting and recognize inputs that were part of training datasets, using the discriminator’s capacity to learn statistical differences in distributions. We present attacks based on both white-box and black-box access to the target model, against several state-of-the-art generative models, over datasets of complex representations of faces (LFW), objects (CIFAR-10), and medical images (Diabetic Retinopathy). We also discuss the sensitivity of the attacks to different training parameters, and their robustness against mitigation strategies, finding that defenses are either ineffective or lead to significantly worse performances of the generative models in terms of training stability and/or sample quality.

Crest module can be defined as the portion of a two-piece implant designed to retain the prosthetic components and to allows the maintenance of the peri-implant tissues in the transition zone. Aim: To evaluate the three-year after loading clinical and radiographic data, collected from patients that received a prosthetic rehabilitation on conical connection implants with partial machined collar (PMC, CC Group) and same body-designed implants, with flat-to-flat connection and groovy neck design (FC Group). Materials and Methods: A retrospective chart review of previously collected data, including documents, radiographs, and pictures of patients who received at least one implant-supported restoration on NobelReplace CC PMC or NobelReplace Tapered Groovy implants was performed. Patients with at least three years of follow-up after final loading were considered for this study. Outcomes measures were implant and prosthesis failures, any biological or technical complications, marginal bone loss. Results: Eight-two patients (44 women, 38 men, average age 55.6) with 152 implants were selected and divided in two groups with 77 (CC group) and 75 (FC group), respectively. Three years after final loading, one implant in CC group failed (98.7% survival rate), while no implants failed in FC group (100% survival rate). One restoration failed in CC group (98.7% survival rate) with no restoration failing in the FC one (100% survival rate). Differences were not statistically significant (p = 1.0). Three years after final loading, mean marginal bone loss was 0.22 &plusmn, 0.06 mm (95% CI 0.2&ndash, 0.24) in CC group and 0.62 &plusmn, 0.30 mm (95% CI 0.52&ndash, 0.72) in FC group. The difference was statistically significant (0.40 &plusmn, 0.13 mm, 95% CI 0.3&ndash, 0.5, p = 0.003). Conclusion: with the limitation of this retrospective comparative study, implants with conical connection and partial machined collar seem to achieve a trend of superior outcomes if compared with implants with flat connection and groovy collar design.

Background Abdominal wall tumors are rare and include heterogeneous diseases. Among them, desmoid tumors are the most frequent and are often diagnosed in young women during or early after pregnancy; inflammatory response after trauma or microtrauma, such as after cesarean section, may favor their growth. Results A 37-year-old woman presented with a progressive mass in the abdominal wall after a cesarean section. Positron emission tomography imaging confirmed a positive mass with a high maximum standardized uptake value; a biopsy suggested a myofibroblastic tumor. With continued tumor growth and worsening symptoms, the mass resembled a desmoid tumor; therefore, we proceed with its resection. The final diagnosis was foreign body granuloma as a reaction to the spillage of meconium and keratinous material in the amniotic fluid during cesarean section. Conclusions The present case provides information on an abdominal wall foreign body granuloma arisen from meconium and vernix caseosa after cesarean section, which presented an atypical clinical picture, mimicking a desmoid, thus requiring a careful diagnostic and treatment approach.

Background.Patients presenting with stage IV breast cancer might benefit by removal of the primary tumor. We report our experience with CT-guided cryoablation of the primary tumor, with the aim of evaluating its role in this subgroup of patients.Patients and Methods.Data of 35 patients with mean age of 58 years with breast cancer at stage IV submitted to CT-guided cryoablation of the primary tumor between 2010 and 2016 were prospectively evaluated. All patients, except three, were preoperatively and postoperatively evaluated with breast MRI to assess the extent of tumor necrosis. Retreatment was performed in case of incomplete ablation.Results.Mean tumor size was 3.02 ± 1.4 cm. Six patients had multicentric disease. Complete tumor necrosis was 85.7% and 100% at 2-month and 6-month follow-up, respectively, as 5 patients with tumors > 3 cm required a redo cryoablation. No patient developed major complications. Minor side effects occurred in 30 patients (82%). All patients were discharged the same day of the procedure. During a mean follow-up of 46 months (range 3–84), 7 patients (20%) experienced local recurrences that were treated with redo cryoablation, and 7 (20%) died for disease progression.Conclusions.Our results suggest that cryoablation of the primary tumor is safe and effective in the treatment of patients presenting with stage IV breast cancer.

Background The treatment of patients with multiple synchronous tumors is challenging and complex. The use of next generation sequencing (NGS) may help in identification of germline mutations in genes involved in a common etiology for both tumors thus allowing a common effective therapeutic strategy. Patients and methods We describe the unexpected positive results obtained in a young woman with relapsed chemo-resistant stage IVB cervical and synchronous stage IV lung cancer, who underwent an interdisciplinary approach including palliative surgery with laparoscopic total pelvic exenteratio followed by a chemo-immunotherapy protocol with the anti-Programmed Death (PD)-1 antibody nivolumab plus metronomic cyclophosphamide. The treatment choice was based on tumor PD-Ligand 1 assessment and NGS analysis for the identification of potential treatment targets. Outcomes included tumor objective response and patient-centered outcomes (pain, performance status and overall quality of life). Results Laparoscopic surgery obtained an immediate symptom control and allowed the early start of medical treatment. One month after combined therapy start the patient achieved a significant improvement in performance status, pain, overall Quality of life and after 3 months she resumed working. After 3 and 6 months of treatment we observed an objective dimensional and metabolic response. Currently, after 24 months (and 48 cycles of nivolumab) the patient is continuing to benefit from treatment: she is in complete remission, with good performance status and she is working and leading a self-dependent life. Conclusion Our study strongly affirms the efficacy of an interdisciplinary approach including surgical and innovative medical strategies based on immunotherapy in patients with advanced chemo-resistant synchronous cervical and lung cancer. The present findings support the use of NGS to drive a targeted rational treatment especially in heavily pre-treated patients.

The role of microwave ablation (MWA) in patients with non-small cell lung cancer (NSCLC) remains ill-defined. This retrospective study evaluated the oncological outcomes of CT-guided MWA in patients with large NSCLC. Kaplan-Meier analysis was used to evaluate overall survival (OS) and cancer-specific survival (CSS). The log-rank test was used to compare survival between patients with an NSCLC size greater or smaller than 4 cm. The likelihood of local tumor progression (LTP) was analyzed using a multivariable regression model. A total of 53 patients with 65 tumors were analyzed. The mean tumor size was 5.0±1.8 cm. At the 1-month CT scan, complete tumor ablation was observed in 44.6% of cases. In 18.5% of cases a redo-MWA session was carried out, while in 4.6%, a third MWA was necessary to obtain complete tumor necrosis. The mean follow-up was 28.1±20.6 months with a median duration of 21.5 months. The 1-year, 2-year, 3-year and 5-year OS rates were 78.2, 48.3, 34.8 and 18.3%, respectively. The median CSS was 25 months (95% CI 15.5-34.5). The 1-year, 2-year, 3-year and 5-year CSS rates were 84.3, 53.7, 42.1 and 30.0%, respectively. OS in patients with tumor size ≥4 cm was significantly lower when compared with those having smaller tumors (P=0.03). LTP was observed in 19 patients (35.8%). Incomplete tumor ablation [odds ratio (OR) 6.57; P

Generative models are used in a wide range of applications building on large amounts of contextually rich information. Due to possible privacy violations of the individuals whose data is used to train these models, however, publishing or sharing generative models is not always viable. In this paper, we present a novel technique for privately releasing generative models and entire high-dimensional datasets produced by these models. We model the generator distribution of the training data with a mixture of $k$ generative neural networks. These are trained together and collectively learn the generator distribution of a dataset. Data is divided into $k$ clusters, using a novel differentially private kernel $k$-means, then each cluster is given to separate generative neural networks, such as Restricted Boltzmann Machines or Variational Autoencoders, which are trained only on their own cluster using differentially private gradient descent. We evaluate our approach using the MNIST dataset, as well as call detail records and transit datasets, showing that it produces realistic synthetic samples, which can also be used to accurately compute arbitrary number of counting queries., A shorter version of this paper appeared at the 17th IEEE International Conference on Data Mining (ICDM 2017). This is the full version, published in IEEE Transactions on Knowledge and Data Engineering (TKDE)