French early nationwide idecabtagene vicleucel chimeric antigen receptor T-cell therapy experience in patients with relapsed/refractory multiple myeloma (FENIX): A real-world IFM study from the DESCAR-T registry.

Idecabtagene vicleucel (ide-cel), a chimeric antigen receptor T-cell therapy targeting B-cell maturation antigen (BCMA), received early access program (EAP) authorization in France in April 2021 for relapsed/refractory multiple myeloma (RRMM). We conducted a real-world registry-based multicentre observational study in 11 French hospitals to evaluate ide-cel outcomes. Data from 176 RRMM patients who underwent apheresis between June 2021 and November 2022 were collected from the French national DESCAR-T registry. Of these, 159 patients (90%) received ide-cel. Cytokine release syndrome occurred in 90% with 2% grade ≥3, and neurotoxicity occurred in 12% with 3% grade ≥3. Over the first 6 months, the best overall response and ≥complete response rates were 88% and 47% respectively. The median progression-free survival (PFS) from the ide-cel infusion was 12.5 months, the median overall survival (OS) was 20.8 months and the estimated OS rate at 12 months was 73.3%. Patients with extra-medullary disease (EMD) had impaired PFS (6.2 months vs. 14.8 months). On multivariable analysis, EMD and previous exposure to BCMA-targeted immunoconjugate or T-cell-redirecting GPRC5D bispecific antibody were associated with inferior PFS. Our study supports ide-cel's feasibility, safety and efficacy in real-life settings, emphasizing the importance of screening for EMD and considering prior treatments to optimize patient selection.

ITI consensus report on zygomatic implants: indications, evaluation of surgical techniques and long-term treatment outcomes.

OBJECTIVES: The aim of the ITI Consensus Workshop on zygomatic implants was to provide Consensus Statements and Clinical Recommendations for the use of zygomatic implants. MATERIALS AND METHODS: Three systematic reviews and one narrative review were written to address focused questions on (1) the indications for the use of zygomatic implants; (2) the survival rates and complications associated with surgery in zygomatic implant placement; (3) long-term survival rates of zygomatic implants and (4) the biomechanical principles involved when zygoma implants are placed under functional loads. Based on the reviews, three working groups then developed Consensus Statements and Clinical Recommendations. These were discussed in a plenary and finalized in Delphi rounds. RESULTS: A total of 21 Consensus Statements were developed from the systematic reviews. Additionally, the group developed 17 Clinical Recommendations based on the Consensus Statements and the combined expertise of the participants. CONCLUSIONS: Zygomatic implants are mainly indicated in cases with maxillary bone atrophy or deficiency. Long-term mean zygomatic implant survival was 96.2% [95% CI 93.8; 97.7] over a mean follow-up of 75.4 months (6.3 years) with a follow-up range of 36-141.6 months (3-11.8 years). Immediate loading showed a statistically significant increase in survival over delayed loading. Sinusitis presented with a total prevalence of 14.2% [95% CI 8.8; 22.0] over a mean 65.4 months follow-up, representing the most common complication which may lead to zygomatic implant loss. The international experts suggested clinical recommendations regarding planning, surgery, restoration, outcomes, and the patient's perspective.

A portable primary-standard level graphite calorimeter for absolute dosimetry in clinical pencil beam scanning proton beams.

Objective. To report the use of a portable primary standard level graphite calorimeter for direct dose determination in clinical pencil beam scanning proton beams, which forms part of the recommendations of the proposed Institute of Physics and Engineering in Medicine (IPEM) Code of Practice (CoP) for proton therapy dosimetry.Approach. The primary standard proton calorimeter (PSPC) was developed at the National Physical Laboratory (NPL) and measurements were performed at four clinical proton therapy facilities that use pencil beam scanning for beam delivery. Correction factors for the presence of impurities and vacuum gaps were calculated and applied, as well as dose conversion factors to obtain dose to water. Measurements were performed in the middle of 10 × 10 × 10 cm3homogeneous dose volumes, centred at 10.0, 15.0 and 25.0 g·cm-2depth in water. The absorbed dose to water determined with the calorimeter was compared to the dose obtained using PTW Roos-type ionisation chambers calibrated in terms of absorbed dose to water in60Co applying the recommendations in the IAEA TRS-398 CoP.Main results.The relative dose difference between the two protocols varied between 0.4% and 2.1% depending on the facility. The reported overall uncertainty in the determination of absorbed dose to water using the calorimeter is 0.9% (k= 1), which corresponds to a significant reduction of uncertainty in comparison with the TRS-398 CoP (currently with an uncertainty equal or larger than 2.0% (k= 1) for proton beams).Significance. The establishment of a purpose-built primary standard and associated CoP will considerably reduce the uncertainty of the absorbed dose to water determination and ensure improved accuracy and consistency in the dose delivered to patients treated with proton therapy and bring proton reference dosimetry uncertainty in line with megavoltage photon radiotherapy.

Prognosis and molecular characteristics of IBD-associated colorectal cancer: Experience from a French tertiary-care center.

BACKGROUND: Little is known about the prognosis of colorectal cancer associated with inflammatory bowel disease (CRC-IBD) in a real-world cohort in France. METHODS: We conducted a retrospective observational study including all patients presenting CRC-IBD in a French tertiary center. RESULTS: Among 6510 patients, the rate of CRC was 0.8% with a median delay of 19.5 years after IBD diagnosis (median age 46 years, ulcerative colitis 59%, initially localized tumor 69%). There was a previous exposure to immunosuppressants (IS) in 57% and anti-TNF in 29% of the cases. A RAS mutation was observed in only 13% of metastatic patients. OS of the whole cohort was 45 months. OS and PFS of synchronous metastatic patients was 20.4 months and 8.5 months respectively. Among the patients with localized tumor those previously exposed to IS had a better PFS (39 months vs 23 months; p = 0.05) and OS (74 vs 44 months; p = 0.03). The IBD relapse rate was 4%. No unexpected chemotherapy side-effect was observed CONCLUSIONS: OS of CRC-IBD is poor in metastatic patients although IBD is not associated with under-exposure or increased toxicity to chemotherapy. Previous IS exposure may be associated with a better prognosis.

Feasibility and Safety of Active Physiotherapy in the Intensive Care Unit for Intubated Patients with Malignancy.

OBJECTIVES: Physiotherapy leads to improvements in critically ill patients who receive mechanical ventilation. However, cancer patients have not been included in previous studies on this subject. This study explored the feasibility and safety of physiotherapy in the intensive care unit for patients with malignancy. DESIGN: Observational prospective single-centre study, comparing cancer and control patients. PATIENTS: All consecutive patients admitted to the intensive care unit who needed invasive mechanical ventilation for more than 2 days with no contraindication to physiotherapy were included in the study. METHODS: The main outcome was the proportion of physiotherapy sessions at the prescribed level in each group. RESULTS: A total of 60 patients were included within 1 year. A total of 576 days were screened for physiotherapy sessions and 367 physiotherapy-days were analysed (137 days for control patients and 230 days for cancer patients). The ratio of physiotherapy sessions performed/prescribed did not differ between groups: 0.78 (0.47-1) in the control group vs 0.69 (0.6-1) in the cancer group (odds ratio 1.18 (IC95% 0.74-1.89); p = 0.23). A sensitivity analysis including patient effect as random variable confirmed those results (odds ratio 1.16 (0.56-2.38), p = 0.69). Adverse events occurred with the same frequency in cancer patients and non-cancer patients. CONCLUSION: Physiotherapy in cancer patients who require intubation is feasible and safe. However, only two-thirds of prescribed physiotherapy sessions were performed. Studies are warranted to explore the barriers to physiotherapy in the intensive care unit setting.

Development of a heterogeneous phantom to measure range in clinical proton therapy beams.

PURPOSE: In particle therapy, determination of range by measurement or calculation can be a significant source of uncertainty. This work investigates the development of a bespoke Range Length Phantom (RaLPh) to allow independent determination of proton range in tissue. This phantom is intended to be used as an audit device. METHOD: RaLPh was designed to be compact and allows different configurations of tissue substitute slabs, to facilitate measurement of range using radiochromic film. Fourteen RaLPh configurations were tested, using two types of proton fluence optimised water substitutes, two types of bone substitute, and one lung substitute slabs. These were designed to mimic different complex tissue interfaces. Experiments were performed using a 115 MeV mono-energetic scanning proton beam to investigate the proton range for each configuration. Validation of the measured film ranges was performed via Monte Carlo simulations and ionisation chamber measurements. The phantom was then assessed as an audit device, by comparing film measurements with Treatment Planning System (TPS) predicted ranges. RESULTS: Varying the phantom slab configurations allowed for measurable range differences, and the best combinations of heterogeneous material gave agreement between film and Monte Carlo on average within 0.2% and on average within 0.3% of ionisation chamber measurements. Results against the TPS suggest a material density override is currently required to enable the phantom to be an audit device. CONCLUSION: This study found that a heterogeneous phantom with radiochromic film can provide range verification as part of a dedicated audit for clinical proton therapy beams.

Daratumumab utilization and cost analysis among patients with multiple myeloma in a US community oncology setting.

Background: The introduction of daratumumab into the treatment of multiple myeloma has improved outcomes in patients; however, community oncologists often dose more frequently than the US FDA-approved label. Materials and methods: Integra analyzed its database to elucidate daratumumab treatment patterns and the impact of increased utilization on the cost of care for multiple myeloma. Results: Following week 24, 671 (65%) of 1037 patients remained on daratumumab-containing regimens, with 330 patients continuing more frequent treatments than the expected once-every-4-weeks dosing described in the standard dosing schedule. Patients received an average of 14% more daratumumab doses than the FDA-approved label indicates, increasing the 1-year daratumumab costs by an estimated US$31,353. Conclusion: Daratumumab is utilized more frequently than the FDA-recommended dosing, leading to higher multiple myeloma treatment costs.

Lay abstract Since its first approval in 2015, daratumumab has become the backbone of many multiple myeloma treatment regimens. While its approval has improved outcomes in many patients who undergo treatment, it is expensive and has largely contributed to the increasing costs of care in multiple myeloma. In its most common treatment schedule, patients should transition from weekly and biweekly dosing to treatment once every 4 weeks. However, many providers maintain their patients on a more frequent dosing schedule, which increases Medicare 1-year costs by an estimated US$31,353 and may have unforeseen impacts on adverse events and patient outcomes.

Management of lung cancer patients' quality of life in clinical practice: a Delphi study.

BACKGROUND: The assessment of health-related quality of life (HRQoL) has seen exponential growth in oncology clinical trials. However, the measurement of HRQoL has yet to be optimised in routine clinical practice. This study aimed at exploring the operationalisation of HRQoL in clinical practice with the goal of reaching a consensus from a panel of physicians. MATERIALS AND METHODS: Physicians involved in the management of lung cancer patients in France were recruited to participate in a Delphi study. The study involved three rounds of iterated queries to gain consensus on management aspects of HRQoL, including timing of discussion on HRQoL, which specific domains of HRQoL should be discussed, and what was the most appropriate method of assessment. The threshold adopted for consensus was at least 70% agreement among physicians. A scientific committee reviewed results following each round of the Delphi study. RESULTS: A representative panel of 60 physicians participated in this study. Consensus was obtained for HRQoL management at all time points in the patient care pathway. Panellists agreed that HRQoL discussions should occur during routine visits and hospitalisation. The involvement of patients' relatives was also recognised as important, except when discussing side-effects and involvement of a multidisciplinary team. There was a lack of consensus on a systematic assessment for all patients at each visit and no consensus on how HRQoL should be measured in clinical practice. CONCLUSIONS: HRQoL discussions are considered an integral part in the management of lung cancer patients, and are deemed key to success in patient-physician interaction. Further research is required to harmonise how best to implement HRQoL assessment.

Predicting the length of stay at admission for emergency general surgery patients a cohort study.

INTRODUCTION: Predicting length of stay (LOS) is beneficial to patients and the health service. When a prolonged LOS is predicted, it gives the opportunity for focused therapies and allocation of resources to reduce this period. In emergency general surgery (EGS) there has been limited investigation of variables that may be important predictors of LOS. This study examines social characteristics alongside measures of severity of acute illness and co-morbidities in an adult EGS population to establish their contribution to LOS. METHODS: Data were collected prospectively from patients at admission including medical variables, demographics, and therapeutic requirements. The length of hospital admission was measured, and multiple regression analysis was used to identify variables which predicted the LOS. RESULTS: Data were collected from 105 patients. The regression model gave an R2 of 0.34, p = 0.0006. Barthal index (measure of independence in activities of daily living) was a significant predictor of LOS [logworth 1.649, p0.02243]. Housing status and Level of social support both correlated in one-way analysis with LOS. CONCLUSION: There are non-surgical variables, measurable at admission which are of significant value in predicting LOS of EGS patients. This warrants further investigation through a larger study to better quantify the contributions of these variables, and establish potential early interventions to reduce the LOS.

Long-term MRI-guided vacuum-assisted breast biopsy results of 600 single-center procedures.

OBJECTIVES: The objective of this study is to report on the performance of the MRI-guided VABB in our center and to look at the long-term outcome of biopsies with benign histology over a period of 19 years. METHODS: In a single-center retrospective review study, data of 600 VABB procedures performed between September 1999 and March 2017 were evaluated. We collected patient demographics, histopathological diagnosis at MRI-VABB, and basic lesion characteristics (size, location). Data from the Belgian Cancer Registry was cross-referenced with our database to find out which patients with benign MRI-VABB results developed a malignant lesion over time. RESULTS: These 600 VABB procedures were performed in 558 women with a mean patient age of 51.8 years (range 18-82 years). Our technical success rate was 99.3%. We found 27.67% B5 lesions, 9.82% B3 lesions, and 0.17% B4 lesions. Of 362 benign MRI-guided VABBs, follow-up data was available for a mean follow-up period of 7.6 years (0.8-18.3). Only one (0.3%) biopsy was a false negative lesion after MRI-guided VABB during follow-up. Short-term FU-MRI provided no increase in detection rate. CONCLUSION: The accuracy of MRI-guided VABB is high with a very low false negative rate of 0.3% on long-term follow-up. The value of short-term FU-MRI for every case after MRI-guided VABB may be questioned. KEY POINTS: • MRI-guided vacuum-assisted breast biopsies yield a large portion of clinically relevant lesions (9.82% B3, 0.17% B4, and 27.67% B5 lesions). • The false negative biopsy rate of MRI-guided VABB in this study with a mean follow-up time of 7.6 years was only 0.3%. • Performing a short-term follow-up MRI after a benign MRI-guided VABB concordant to the MRI appearance may be questioned.

Alopecia areata: a review on diagnosis, immunological etiopathogenesis and treatment options.

Patients suffering from alopecia areata (AA) can lose hair in focal regions, the complete scalp, including eyelashes and eyebrows, or even the entire body. The exact pathology is not yet known, but the most described theory is a collapse of the immune privilege system, which can be found in some specific regions of the body. Different treatment options, local and systemic, are available, but none of them have been proven to be effective in the long term as well for every treatment there should be considered for the possible side effects. In many cases, treated or non-treated, relapse often occurs. The prognosis is uncertain and is negatively influenced by the subtypes alopecia totalis and alopecia universalis and characteristics such as associated nail lesions, hair loss for more than 10 years and a positive familial history. The unpredictable course of the disease also makes it a mental struggle and AA patients are more often associated with depression and anxiety compared to the healthy population. Research into immunology and genetics, more particularly in the field of dendritic cells (DC), is recommended for AA as there is evidence of the possible role of DC in the treatment of other autoimmune diseases such as multiple Sclerosis and cancer. Promising therapies for the future treatment of AA are JAK-STAT inhibitors and PRP.

Developments and challenges in dermatology: an update from the Interactive Derma Academy (IDeA) 2019.

The 2019 Interactive Derma Academy (IDeA) meeting was held in Lisbon, Portugal, 10-12 May, bringing together leading dermatology experts from across Europe, the Middle East and Asia. Over three days, the latest developments and challenges in relation to the pathophysiology, diagnosis, evaluation and management of dermatological conditions were presented, with a particular focus on acne, atopic dermatitis (AD) and actinic keratosis (AK). Interesting clinical case studies relating to these key topics were discussed with attendees to establish current evidence-based best practices. Presentations reviewed current treatments, potential therapeutic approaches and key considerations in the management of acne, AK and AD, and discussed the importance of the microbiome in these conditions, as well as the provision of patient education/support. It was highlighted that active treatment is not always required for AK, depending on patient preferences and clinical circumstances. In addition to presentations, two interactive workshops on the diagnosis and treatment of sexually transmitted infections/diseases (STIs/STDs) presenting to the dermatology clinic, and current and future dermocosmetics were conducted. The potential for misdiagnosis of STIs/STDs was discussed, with dermoscopy and/or reflectance confocal microscopy suggested as useful diagnostic techniques. In addition, botulinum toxin was introduced as a potential dermocosmetic, and the possibility of microbiome alteration in the treatment of dermatological conditions emphasized. Furthermore, several challenges in dermatology, including the use of lasers, the complexity of atopic dermatitis, wound care, use of biosimilars and application of non-invasive techniques in skin cancer diagnosis were reviewed. In this supplement, we provide an overview of the presentations and discussions from the fourth successful IDeA meeting, summarizing the key insights shared by dermatologists from across the globe.

Practical recommendations for systemic treatment in psoriasis in case of coexisting inflammatory, neurologic, infectious or malignant disorders (BETA-PSO: Belgian Evidence-based Treatment Advice in Psoriasis; part 2).

BACKGROUND: Psoriasis patients carry an increased risk for associated comorbidities. Dermatologists have to be aware of the effects of systemic treatments not only on psoriasis but also on co-occurring diseases. In case of other coexisting inflammatory diseases, the right psoriasis treatment may improve both disorders. For infectious and malignant disorders, some treatments have to be avoided as they may be harmful. OBJECTIVE: The primary objective of this project was to collect evidence for the creation of practice guidelines for systemic treatment of psoriasis (BETA-PSO: Belgian Evidence-based Treatment Advice in Psoriasis). METHODS: Evidence-based recommendations were formulated using a quasi-Delphi methodology after a systematic search of the literature and a consensus procedure involving eight psoriasis experts. RESULTS: Recommendations are given on the use of systemic treatment in psoriatic arthritis, inflammatory bowel disease, demyelinating disorders, hepatitis B and C, HIV and cancer. CONCLUSION: This expert opinion is a practical guide for dermatologists when handling psoriasis patients with these specific conditions.

Efficacy and safety of aerosolized intra-tracheal dornase alfa administration in patients with SARS-CoV-2-induced acute respiratory distress syndrome (ARDS): a structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) may trigger severe pneumonia in coronavirus disease of 2019 (COVID-19) patients through release of damage-associated molecular patterns (DAMPs) and recruitment of neutrophils in the lungs. Activated neutrophils induce inflammation and severe alveolar injury by releasing neutrophil extracellular traps (NETs). The backbones of many DAMPs and NETs are made of extracellular, cell-free DNA decorated with highly toxic compounds such as elastase, myeloperoxidase and citrullinated histones. Dornase alfa is a FDA-approved recombinant human DNAse 1 for the treatment of cystic fibrosis, which cleaves extracellular DNA and may break up cell-free DNA, loosening sticky mucus in the distal airways and reducing NETs-induced toxicity on alveolar pneumocytes. The COVIDornase trial intends to define the impact of aerosolized intra-tracheal dornase alfa administration on the severity and progression of acute respiratory distress syndrome (ARDS) in COVID-19 patients. This drug might make lung mucus thinner and looser, promoting improved clearance of secretions and reduce extracellular double-stranded DNA-induced hyperinflammation in alveoli, preventing further damage to the lungs. TRIAL DESIGN: COVIDornase is a prospective, randomized, controlled, 2-arm (1:1 ratio), multicentric, open-label clinical trial. PARTICIPANTS: The study will recruit mechanically ventilated patients hospitalized in the intensive care unit (ICU) in the recruiting centres (at the time of writing: The Rothschild foundation hospital in Paris, the Strasbourg university hospitals, and Metz-Thionville hospital) who have been diagnosed with COVID-19 and meet ARDS criteria. INCLUSION CRITERIA: - Adult patient (age ≥ 18 years old); - Hospitalized in ICU; - With severe COVID-19 pneumonia and ARDS according to Berlin criteria (PaO2/FiO2 < 300 and PEEP > 5 cmH2O); - Intubated for less than 8 days; - With an anticipated duration of mechanical ventilation > 48 hours; - Carrier of an arterial catheter; - For whom 4 PaO2/FiO2 values over the preceding 24 hours are available; NON-INCLUSION CRITERIA: - Known hypersensitivity to dornase alfa or any of its excipients; - Pregnant or breastfeeding status; - Patient under legal protection. INTERVENTION AND COMPARATOR: Intervention 1, Study group Dornase alfa (Pulmozyme®, Roche, Switzerland) will be administered by aerosol, at a dose of 2500 IU twice daily, 12 hours apart, for 7 consecutive days, using a vibrating mesh nebulizer (Aerogen Solo®, Aerogen, Ireland). The remainder of the management will be performed in accordance with good clinical practice, including mechanical ventilation (protective ventilation, PEEP > 5 cmH2O, tracheal balloon pressure check every 4 hours or automatic device, 30° head of the bed elevation, tidal volume 6-8mL/kg, plateau pressure < 30 cmH2O), neuromuscular blockers if necessary, prone position if PaO2/FiO2 < 150, early enteral nutrition, glycemic control and a sedation protocol based on the RASS score. Intervention 2, Comparator Patients will receive usual care in accordance with good practice (as detailed above), without aerosols. MAIN OUTCOMES: The primary outcome is the occurrence of at least one grade improvement between D0 (inclusion) and D7 in the ARDS scale severity (Berlin criteria). For instance from "severe" to "moderate" or from "moderate" to "mild". RANDOMISATION: All consecutive patients meeting the inclusion criteria will be randomised 1:1 using an eCRF-based, computer-generated randomisation table, either to the dornase alfa arm or to the control arm. An interim analysis will be performed after inclusion of 20 patients. Inclusions may be stopped at the interim analysis per data safety and monitoring board (DSMB) advice, if statistical analyses conclude on the futility or efficacy of the intervention or by other DSMB decision. BLINDING (MASKING): The participants and caregivers will not be blinded to study group assignment. Those assessing the outcomes will be blinded to study group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Fifty patients will be randomized to each group, 100 patients in total. TRIAL STATUS: Protocol version number 2, April 29th, 2020. Recruitment is ongoing. The trial started recruitment on the 21st April 2020. We estimate recruitment will finish August 21st 2020. TRIAL REGISTRATION: The trial was registered in ClinicalTrials.gov on 21 April 2020, updated on 8 May 2020. Trial registration number is NCT04355364. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated. This Letter serves as a summary of the key elements of the full protocol.

Prognosis of Lymphoma in Patients With Known Inflammatory Bowel Disease: A French Multicentre Cohort Study.

BACKGROUND AND AIMS: The prognosis of lymphoma that occurs in patients with inflammatory bowel disease [IBD] is poorly known. METHODS: A multicentre retrospective cohort analysis was done in seven French tertiary centres from 1999 to 2019. Only lymphoma occurring in patients with previous established diagnosis of IBD were analysed. The primary outcome was progression-free survival at 3 years. RESULTS: A total of 52 patients [male 65%, Crohn's disease 79%, median age 48.3 years, median duration of IBD 10.1 years] were included, of whom 37 had been previously exposed to immunosuppressants and/or biologics for at least 3 months and 20 had primary intestinal lymphomas. The lymphoma histological types were: diffuse large B cell lymphomas [N = 17], Hodgkin lymphomas [N = 17], indolent B cell lymphomas [N = 12], and others including T cell lymphomas, mantle cell lymphomas, and unclassifiable B cell lymphoma [N = 6]. The median follow-up after lymphoma was 5.1 years (interquartile range [IQR] 4-7.8). Progression-free survival at 3 years was 85% in the overall population (95% confidence interval [CI] 75%-96%) with no significant difference between the exposed and unexposed group, 79% for patients exposed to immunosuppressants and/or biologics [95% CI 67%-94%], and 83% for patients diagnosed with primary intestinal lymphoma [95% CI 67%-100%]. No relapse of IBD has been observed during chemotherapy. The IBD relapse rate at the end of the last chemotherapy cycle was 23% at 3 years [95% CI 11%-39%] in the overall population. CONCLUSIONS: In this large cohort, the prognosis for lymphomas occurring in IBD appears to be good and similar to what is expected, irrespective of the exposure to biologics and/or immunosuppressants.

Development and internal validation of a diagnostic score for gastric linitis plastica.

BACKGROUND: There is no consensual definition for gastric linitis plastica (GLP). We aim to construct a diagnostic score to distinguish this rare tumor from usual gastric adenocarcinomas. METHODS: In this retrospective study, all patients who had gastrectomy for cancer between 2007 and 2017 in French tertiary centers were included. The outcome was a diagnosis of GLP based on pathological review of the surgical specimen. The diagnostic score was created by using variables that were most frequently associated with GLP using penalized logistic regression on multiply imputed datasets. We used discrimination measures to assess the performances of the score. Internal validation was performed using bootstrapping methods to correct for over-optimism. RESULTS: 220 patients including 71 linitis plastica (female 49%, median age 57 years) were analyzed. The six parameters retained in the diagnosis score were the presence of large folds and/or parietal thickening on at least one segment, pangastric infiltration and presence of gastric stenosis on the upper endoscopy, circumferential thickening on at least one segment and thickening of the third hyperechogenic layer on endoscopic ultrasound and the presence of signet ring cells on endoscopic biopsies. The area under the ROC curve (AUC) was 0.967 with a sensitivity of 94% [89.9-97.3] and a specificity of 88.7% [81.7-95.8] for a threshold of 2.75. After internal validation, the corrected AUC was 0.959. CONCLUSION: It is the first study validating a pre-therapeutic diagnostic score (Saint Louis linitis score) with an excellent ability to discriminate GLP from non-GLP adenocarcinomas. An external validation is necessary to confirm our data.

Stage IV cutaneous squamous cell carcinoma: treatment outcomes in a series of 42 patients.

BACKGROUND: The prevalence and incidence of cutaneous squamous cell carcinoma (cSCC) are increasing due to the ageing of the population and sun exposure. Advanced cSCC forms (locally advanced and/or locoregional metastatic and/or distant metastatic) account for approximately 3% of cSCC and can result in death. OBJECTIVE: Analysis of the clinical characteristics and treatment outcomes in stage IV cSCC with unresectable locoregional extension and/or the presence of metastases. METHODS: A retrospective study was conducted at a single-centre university hospital for stage IV cSCC patients followed between 1 January 2008 and 31 December 2015. Descriptive analyses (demographic, anatomo-clinical characteristics, treatment sequences, response to treatment and survival analysis) were performed. RESULTS: The study included 42 patients (median age = 75.5 years) with a diagnosis of stage IV cSCC who were treated with at least one line of chemotherapy and/or cetuximab. At the time of diagnosis, 85.7% of the patients had locoregional extension (19% of locally advanced and 67% of locoregional metastatic) and 14.3% had distant metastatic disease. Regarding treatment, 40% and 36% of patients received no more than 1 and 2 systemic treatment lines, respectively. The 4-year overall survival was 6%, and the median follow-up was 18.6 months. The objective response rate was 55% after the first line of treatment with a median progression-free survival (PFS) of 6.18 months and 12% after the second line with a median PFS of 6.51 months. Grade 3 and 4 adverse events were observed for 33% of patients. CONCLUSION: Our study confirms a very poor prognosis of stage IV cSCC and a poor response to conventional therapies, indicating that the stage IV cSCC patient population remains with unmet medical needs.

Accelerated Tissue Processing With Minimal Formalin Fixation Time for 9-Gauge Vacuum-Assisted Breast Biopsy Specimens.

OBJECTIVES: Vacuum-assisted biopsy (VAB) of the breast seems unsuitable for rapid processing due to large size. We tested microwave-based acceleration. METHODS: As a proof-of-principle study, 9-gauge VAB specimens were taken from eight mastectomy specimens. Forty-two biopsy specimens were processed. Quality of H&E was evaluated in 84 slides, and estrogen receptor (ER), progesterone receptor (PR), E-cadherin, and human epidermal growth factor receptor 2 (HER2) stains were evaluated in six slides. Preoperative biopsy specimens were used as a control. RESULTS: Diagnostic quality of H&E slides was good in 87%, reasonable in 12%, and low in 1%. Quality of E-cadherin was good in 75% and reasonable in 25%. Quality of ER was good in 83% and reasonable in 17%. PR and both HER2 immunohistochemistry and fluorescence in situ hybridization were good in all slides. Quality of experimental slides was similar to control slides. CONCLUSIONS: Nine-gauge VAB specimens can be processed within 4 hours. Slides are suitable for all routine pathologic stains. This enables a same-day diagnosis.

Epidemiologic evaluation of Nhanes for environmental Factors and periodontal disease.

Periodontitis is a chronic inflammation that destroys periodontal tissues caused by the accumulation of bacterial biofilms that can be affected by environmental factors. This report describes an association study to evaluate the relationship of environmental factors to the expression of periodontitis using the National Health and Nutrition Examination Study (NHANES) from 1999-2004. A wide range of environmental variables (156) were assessed in patients categorized for periodontitis (n = 8884). Multiple statistical approaches were used to explore this dataset and identify environmental variable patterns that enhanced or lowered the prevalence of periodontitis. Our findings indicate an array of environmental variables were different in periodontitis in smokers, former smokers, or non-smokers, with a subset of specific environmental variables identified in each population subset. Discriminating environmental factors included blood levels of lead, phthalates, selected nutrients, and PCBs. Importantly, these factors were found to be coupled with more classical risk factors (i.e. age, gender, race/ethnicity) to create a model that indicated an increased disease prevalence of 2-4 fold across the sample population. Targeted environmental factors are statistically associated with the prevalence of periodontitis. Existing evidence suggests that these may contribute to altered gene expression and biologic processes that enhance inflammatory tissue destruction.