Multiple surgical resections for progressive IDH wildtype glioblastoma-is it beneficial?

PURPOSE: The role of repeat resection for recurrent glioblastoma (rGB) remains equivocal. This study aims to assess the overall survival and complications rates of single or repeat resection for rGB. METHODS: A single-centre retrospective review of all patients with IDH-wildtype glioblastoma managed surgically, between January 2014 and January 2022, was carried out. Patient survival and factors influencing prognosis were analysed, using Kaplan-Meier and Cox regression methods. RESULTS: Four hundred thirty-two patients were included, of whom 329 underwent single resection, 83 had two resections and 20 patients underwent three resections. Median OS (mOS) in the cohort who underwent a single operation was 13.7 months (95% CI: 12.7-14.7 months). The mOS was observed to be extended in patients who underwent second or third-time resection, at 22.9 months and 44.7 months respectively (p < 0.001). On second operation achieving > 95% resection or residual tumour volume of < 2.25 cc was significantly associated with prolonged survival. There was no significant difference in overall complication rates between primary versus second (p = 0.973) or third-time resections (p = 0.312). The use of diffusion tensor imaging (DTI) guided resection was associated with reduced post-operative neurological deficit (RR 0.37, p = 0.002), as was use of intraoperative ultrasound (iUSS) (RR 0.45, p = 0.04). CONCLUSIONS: This study demonstrates potential prolongation of survival for rGB patients undergoing repeat resection, without significant increase in complication rates with repeat resections. Achieving a more complete repeat resection improved survival. Moreover, the use of intraoperative imaging adjuncts can maximise tumour resection, whilst minimising the risk of neurological deficit.

Zinc levels of patients with a moderate to severe COVID-19 infection at hospital admission and after 4th days of ward hospitalization and their clinical outcome.

BACKGROUND: Previous studies associate the disturbance of the Zinc (Zn) status with the severity of the disease and the inflammatory process in the critically ill patient. This decrease in Zn concentrations is an indicator of poor prognosis. Our aim was to evaluate Zn levels at admission and after four days, and to study if lower Zn levels at those days were related to a worse clinical outcome. MATERIAL AND METHODS: Observational cohort study at a tertiary Hospital. Recruitment period: 09/04/2020-04/24/2021. Clinical information on hypertension, diabetes mellitus (DM), chronic obstructive pulmonary disease (COPD), or bronchial asthma was collected. Obesity was defined as BMI ≥ 30 Kg/m2. Blood extraction was performed at admission and after 4 days. Zn was measured by atomic absorption using a flame method. Worse clinical outcome was defined as death during admission, intensive critical care unit admission or receiving supplemental oxygen through noninvasive or invasive ventilator care. RESULTS: 129 subjects were invited to participate but only 100 subjects completed the survey. According to ROC curve [AUC= 0.63 (95% CI 0.60-0.66)], Zn < 79 µg/dL showed the best performance to detect a worse outcome (Sn=0.85; Sp=0.36). Patients with Zn < 79 µg/dL were older (70 vs 61 y; p = 0.002) with no differences by sex. Most patients presented with fever, dysthermic symptoms and cough, without differences between groups. Pre-existing comorbid conditions did not differ significantly between groups. Less obese subjects were found in the Zn < 79 µg/dL group (21.4 vs 43.3%, p = 0.025). In the univariate analysis, Zn < 79 µg/dL at hospital admission was related to a worse outcome (p = 0.044), but after adjusting for age, C-reactive protein, and obesity there was no difference, but a tendency towards a worse prognosis [OR 2.20 (0.63-7.70), p = 0.215]. Zn levels increased in both groups after 4 days (66.6 vs 73.1 µg/dL at admission, and 72.2 vs 80.5 µg/dL at 4th day), with ns. difference (p = 0.214). CONCLUSION: Zn < 79 µg/dL at admission for a moderate to severe COVID-19 infection could be related to a worse outcome, although after adjustment for age, C-reactive protein levels and obesity, this Zn level threshold did not show statistically significant difference in the composite end point, but a tendency towards a worse prognosis. In addition, patients with the best clinical evolution showed higher serum Zn levels at 4th day after hospital admission than the patients with a worse prognosis.

Same-day SARS-CoV-2 antigen test screening in an indoor mass-gathering live music event: a randomised controlled trial.

BACKGROUND: The banning of mass-gathering indoor events to prevent SARS-CoV-2 spread has had an important effect on local economies. Despite growing evidence on the suitability of antigen-detecting rapid diagnostic tests (Ag-RDT) for mass screening at the event entry, this strategy has not been assessed under controlled conditions. We aimed to assess the effectiveness of a prevention strategy during a live indoor concert. METHODS: We designed a randomised controlled open-label trial to assess the effectiveness of a comprehensive preventive intervention for a mass-gathering indoor event (a live concert) based on systematic same-day screening of attendees with Ag-RDTs, use of facial masks, and adequate air ventilation. The event took place in the Sala Apolo, Barcelona, Spain. Adults aged 18-59 years with a negative result in an Ag-RDT from a nasopharyngeal swab collected immediately before entering the event were randomised 1:1 (block randomisation stratified by age and gender) to either attend the indoor event for 5 hours or go home. Nasopharyngeal specimens used for Ag-RDT screening were analysed by real-time reverse-transcriptase PCR (RT-PCR) and cell culture (Vero E6 cells). 8 days after the event, a nasopharyngeal swab was collected and analysed by Ag-RDT, RT-PCR, and a transcription-mediated amplification test (TMA). The primary outcome was the difference in incidence of RT-PCR-confirmed SARS-CoV-2 infection at 8 days between the control and the intervention groups, assessed in all participants who were randomly assigned, attended the event, and had a valid result for the SARS-CoV-2 test done at follow-up. The trial is registered at ClinicalTrials.gov, NCT04668625. FINDINGS: Participant enrollment took place during the morning of the day of the concert, Dec 12, 2020. Of the 1140 people who responded to the call and were deemed eligible, 1047 were randomly assigned to either enter the music event (experimental group) or continue with normal life (control group). Of the 523 randomly assigned to the experimental group, 465 were included in the analysis of the primary outcome (51 did not enter the event and eight did not take part in the follow-up assessment), and of the 524 randomly assigned to the control group, 495 were included in the final analysis (29 did not take part in the follow-up). At baseline, 15 (3%) of 495 individuals in the control group and 13 (3%) of 465 in the experimental group tested positive on TMA despite a negative Ag-RDT result. The RT-PCR test was positive in one case in each group and cell viral culture was negative in all cases. 8 days after the event, two (<1%) individuals in the control arm had a positive Ag-RDT and PCR result, whereas no Ag-RDT nor RT-PCR positive results were found in the intervention arm. The Bayesian estimate for the incidence between the experimental and control groups was -0·15% (95% CI -0·72 to 0·44). INTERPRETATION: Our study provides preliminary evidence on the safety of indoor mass-gathering events during a COVID-19 outbreak under a comprehensive preventive intervention. The data could help restart cultural activities halted during COVID-19, which might have important sociocultural and economic implications. FUNDING: Primavera Sound Group and the #YoMeCorono Initiative. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Cardiac and Skeletal Muscle Metastases From Squamous Cell Carcinoma of the Bladder: Positron Emission Tomography-Computed Tomography Findings.

We describe the positron emission tomography-computed tomography (PET-CT) findings of a patient who presented to the emergency room with chest pain and palpitations and underwent a radical cystectomy 6 months earlier because of a squamous cell carcinoma of the bladder (SCCB). Cardiac catheterization ruled out coronary artery occlusion, but PET-CT showed multiple F-18-fluorodeoxyglucose-avid lesions involving multiple skeletal muscles and the heart, consistent with metastases. A CT-guided biopsy of 1 skeletal muscle lesion confirmed a metastasis with the same pathologic features as the SCCB. To our knowledge, this is the first reported case of an SCCB with metastases to multiple skeletal muscles and myocardium detected with PET-CT.

High-dose-rate brachytherapy boost effect on local tumor control in young women with breast cancer.

PURPOSE: To evaluate the local control rate and complications of a single fraction of high-dose-rate brachytherapy (HDR BT) boost in women aged 45 yeas and younger after breast-conserving therapy. METHODS AND MATERIALS: Between 1999 and 2007, 167 patients between the ages of 26 and 45 years old (72 were 40 years old or younger), with stages T1 to T2 invasive breast cancer with disease-free margin status of at least 5 mm after breast-conserving surgery received 46 to 50 Gy whole-breast irradiation plus a 7-Gy HDR-BT boost ("fast boost"). An axillary dissection was performed in 72.5% of the patients and sentinel lymph node biopsy in 27.5%. A supraclavicular area was irradiated in 19% of the patients. Chemotherapy was used in 86% of the patients and hormone treatment in 77%. Clinical nodes were present in 18% and pathological nodes in 29%. The pathological stage was pT0: 5%, pTis: 3%, pT1: 69% and pT2: 23%. Intraductal component was present in 40% and 28% were G3. RESULTS: At a median follow-up of 92 months, 9 patients relapsed on the margin of the implant, and 1 patient in another quadrant, resulting in a 10-year local relapse rate of 4.3% and a breast relapse rate of 4.9%, with breast preservation in 93.4%; no case of mastectomy due to poor cosmesis arose. Actuarial 5- and 10-year disease-free, cause-specific, and overall survival rates were 87.9% and 85.8%, and 92.1% and 88.4%, and 92.1% and 87.3%, respectively. In a univariate analysis, triple-negative cases and negative hormone receptors did worse, but in a multivariate analysis, only the last factor was significant for local and breast control. Asymptomatic fibrosis G2 was recorded in 3 cases, and there were no other late complications. Cosmetic results were good to excellent in 97% of cases. CONCLUSIONS: A single dose of 7 Gy using the fast-boost technique is well tolerated, with a low rate of late complications and improved local tumor control in women aged 45 and younger, compared to published data. This approach is recommended in breast-preserving treatment.

Probing hidden sectors with Stückelberg U(1) gauge fields.

We propose a framework in which visible matter interacts with matter from a hidden sector through mass mixings of Stückelberg U(1) gauge fields. In contrast to other Z(') mediation scenarios, our setup has the added appealing features that (i) the choice of Z(')'s can be significantly broadened without necessarily introducing unwanted exotic matter and (ii) there can be sizable tree-level interactions between the visible and hidden sectors. String theory embeddings of this scenario and their phenomenological features are briefly discussed.

Mejora en el control local en mujeres jóvenes con cáncer de mama precoz añadiendo una sola fracción de braquiterapia de alta tasa de dosis / Improved local control in young women with early-stage breast cancer by adding a single fraction of high-dose-rate brachytherapy

Objetivo. Evaluar la eficacia de la braquiterapia con iridio-192 de alta tasa de dosis con una sola fracción como sobreimpresión después de irradiar la mama en mujeres de hasta 45 años. Pacientes y métodos. Se estudiaron 167 pacientes consecutivas con tumores T1-2, entre 26-45 años, sometidas a cirugía conservadora con bordes libres y radioterapia (46-50 Gy) por carcinoma de mama infiltrante entre 1999 y 2008. Se realizó implante con agujas metálicas paralelas bajo anestesia local y sedación de forma ambulatoria. La quimioterapia se utilizó en el 85% (66% adyuvante, 19% neoadyuvante) y la hormonoterapia en el 77%. Se administró una dosis única de 7 Gy con braquiterapia de alta tasa de dosis (fast-boost). Resultados. El seguimiento mediano fue de 69 meses. Ocho pacientes recayeron en el lecho o en el margen tumoral con un control actuarial local de 95,6% a 10 años (tasa de recaída 4,4%). Hubo una recaída en otro cuadrante, por tanto, el control local en la mama fue de 94,1%. Las pacientes hasta 40 años recayeron en la mama en un 6,9% a los 10 años. Ventidós pacientes desarrollaron metástasis. La supervivencia libre de enfermedad y global fue de 85,5 y 92%, respectivamente. Los resultados cosméticos fueron buenos/excelentes en el 97%. La toxicidad aguda y tardía fueron mínimas. Conclusiones. El fast-boost con una sola fracción es una técnica rápida, sencilla y eficaz cuando los márgenes quirúrgicos están libres. El control local en las mujeres jóvenes se ha mejorado respecto a la literatura, por lo que se recomienda la preservación de la mama con este esquema

Objective. To evaluate the effectiveness of a single fraction of high-dose-rate iridium-192 brachytherapy as a boost after irradiation of the breast in women aged 45 or less. Patients and methods. We studied 167 consecutive patients with T1-2 tumors, aged between 26 and 45 years undergoing conservative surgery with free margins and radiotherapy (46-50 Gy) for invasive breast carcinoma between 1999 and 2008. Parallel metal needles were implanted under local anesthesia and sedation on an outpatient basis. Chemotherapy was used in 85% (66% adjuvant and 19% neoadjuvant) and hormonal therapy in 77%. A single 7 Gy-dose of high-dose rate brachytherapy ("fast boost") was administered. Results. The median follow-up was 69 months. In 8 patients, recurrences occurred in the tumor bed or in the margin with an actuarial local control of 95.6% at 10 years (relapse rate 4.4%). There was a relapse in another quadrant and therefore breast control was 94.1%. In patients aged up to 40 years, the breast failure rate was 6.9% at 10 years. Metastases developed in 22 patients. Disease-free survival was 85.5% and overall survival was 92%. Cosmetic results were good or excellent in 97% and acute and late toxicity was minimal. Conclusions. The fast boost technique with a single fraction is fast, simple, and effective when surgical margins are free. Local control in young women has improved compared with prior reports in the literature. Therefore, this technique can be recommended for breast preservation

Millicharged dark matter in quantum gravity and string theory.

We examine the millicharged dark matter scenario from a string theory perspective. In this scenario, kinetic and mass mixings of the photon with extra U(1) bosons are claimed to give rise to small electric charges, carried by dark matter particles, whose values are determined by continuous parameters of the theory. This seems to contradict folk theorems of quantum gravity that forbid the existence of irrational charges in theories with a single massless gauge field. By considering the underlying structure of the U(1) mass matrix that appears in type II string compactifications, we show that millicharges arise exclusively through kinetic mixing, and require the existence of at least two exactly massless gauge bosons.

Ten-year results of a phase II study with a single fraction of high-dose-rate brachytherapy (FAST-boost) after whole breast irradiation in invasive breast carcinoma.

PURPOSE: We present the results of a prospective ten-year follow-up study to prove the effectiveness of a single fraction of 192-Ir high-dose-rate (HDR) brachytherapy (BT) as a boost. PATIENTS AND METHODS: Between 1999 and 2000, 84 consecutive patients with invasive breast carcinoma, with over 4 mm free margins after conservative surgery, were treated. All cases were stages T1-2, except for one case, a stage T3, 81% pN0, 19% pN1-2. Chemotherapy was used in 47% and hormonal therapy in 87%. Whole breast external beam radiotherapy (46 Gy) was followed 1-2 weeks later by an implant with metallic needles. A 7 Gy single dose of HDR BT to the 90% isodose line was delivered on an outpatient basis. Dosimetry was performed theoretically. This technique is called FAST-boost because the whole treatment is delivered in about two hours. RESULTS: With a median follow-up of 120 months, three patients relapsed in the margin of the implant and two in a different quadrant (5/84, 6%). Actuarial local control at five and ten years was 98.5% and 95.6%. Overall survival was 92.7% and 90.2%, and disease-free survival 90.2% and 79.9%. Cosmetic results were good or excellent in 92.5%. CONCLUSIONS: A single-fraction HDR boost with rigid needles (FAST-boost) is a good, quick, simple technique when surgical margins are free.