Outcomes and clinical characteristics of the compassionate use of plitidepsin in COVID-19 patients with solid tumours, haematological malignancies or anti-CD20 antibody treatment.

OBJECTIVE: To study the effect of plitidepsin antiviral treatment in immunocompromised COVID-19 patients with underlying haematological malignancies or solid tumours, particularly those who have undergone anti-CD20 therapies. DESIGN: We conducted a retrospective observational study, involving 54 adults treated with plitidepsin on compassionate use as an antiviral drug. Our analysis compared outcomes between patients with solid tumours and those with haematological malignancies, and a cohort of cases treated or not with anti-CD20 monoclonal antibodies. RESULTS: Patients with a history of anti-CD20 therapies showed a prolonged time-to-negative RT-PCR for SARS-CoV-2 infection compared to non-treated patients (33 d (28;75) vs 15 (11;25); p = .002). Similar results were observed in patients with solid tumours in comparison to those with haematological malignancies (13 (10;16) vs 26 (17;50); p < .001). No serious adverse events were documented. CONCLUSIONS: Patients with haematological malignancies appear to be at a heightened risk for delayed SARS-CoV-2 clearance and subsequent clinical complications. These findings support plitidepsin as a well-tolerated treatment in this high-risk group. A phase II clinical trial (NCT05705167) is ongoing to evaluate plitidepsin as an antiviral drug in this population.KEY POINTSHaematological patients face an increased risk for severe COVID-19.Anti-CD20 therapies could increase fatal outcomes in COVID-19 patients.Persistent viral replication is increased in immunocompromised patients.Plitidepsin does not lead to new serious adverse events in immunocompromised patients.

How to Study the Location and Size of Rectal Tumors That Are Candidates for Local Surgery: Rigid Rectoscopy, Magnetic Resonance, Endorectal Ultrasound or Colonoscopy? An Interobservational Study.

1. BACKGROUND: Preoperative staging of rectal lesions for transanal endoscopic surgery (TES) comprises digital rectal examination, intraoperative rigid rectoscopy (IRR), endorectal ultrasound (EUS), colonoscopy and rectal magnetic resonance imaging (rMRI). The gold standard for topographic features is IRR. Are the results of the other tests sufficiently reliable to eliminate the need for IRR? rMRI is a key test in advanced rectal cancer and is not operator-dependent. Description of anatomical landmarks is variable. Can we rely on the information regarding topographic features provided by all radiologists? 2. MATERIALS AND METHODS: This is a concordance interobservational study involving four diagnostic tests of anatomical characteristics of rectal lesions (colonoscopy, EUS, rectal MRI and IRR), performed by four expert radiologists, regarding topographic rectal features with rMRI. 3. RESULTS: Fifty-five rectal tumors were operated on by using TES. The distance of the tumor from the anal verge, location by quadrants, size by quadrants and size of tumor were assessed (IRR as gold standard). For most of the tumors, the correlation between IRR and colonoscopy or EUS was very good (ICC > 0.75); the correlation between rMRI and IRR in respect of the size by quadrants (ICC = 0.092) and location by quadrants (ICC = 0.292) was weak. Topographic landmarks studied by the expert radiologists had an excellent correlation, except for distance from the peritoneal reflection to the anal verge (ICC = 0.606). 4. CONCLUSIONS: Anatomical description of rectal lesions by IRR, EUS, colonoscopy and rMRI is reliable. Topographic data obtained by EUS and colonoscopy can serve as a reference to avoid IRR. Determination of these topographic data by rMRI is less reliable. As performed by the expert radiologists, the anatomical study by rMRI is accurate and reproducible.

Outcomes and clinical characteristics of the compassionate use of plitidepsin for immunocompromised adult patients with COVID-19.

OBJECTIVES: To evaluate the compassionate use of plitidepsin as an antiviral treatment in hospitalized immunocompromised adult patients with moderate-to-severe COVID-19. DESIGN: Retrospective observational study of data -collected from January 01, 2021 to April 30, 2022- from 35 immunocompromised adult patients with COVID-19 non-eligible for other available antiviral treatments. Main outcome measures were time to respiratory recovery (SpFi ≥ 315); COVID-19-related 30-day-cumulative mortality after first plitidepsin infusion; and time to undetectable levels of viral RNA. RESULTS: Thirty-three patients receiving a full course of plitidepsin (2.5 mg [n = 29] or 1.5 mg [n = 4]) were included. Most (69.7%) had a malignant hematologic disease and 27.3% had solid tumors. A total of 111 infusions were administered with lack of relevant safety events. Median time from plitidepsin initiation to SpFi ≥315 was 8 days (95% confidence interval [CI], 7-19). Median time to first negative reverse transcription-polymerase chain reaction for SARS-CoV-2 (cycle threshold >36) was 17 days (95% CI 13-25). Mortality rate was 16.3% (95% CI 3-37.3). CONCLUSION: These data support plitidepsin as a well-tolerated treatment that might have potential clinical and antiviral efficacy in COVID-19 immunocompromised patients.

Clinical characteristics and outcomes among hospitalized adults with severe COVID-19 admitted to a tertiary medical center and receiving antiviral, antimalarials, glucocorticoids, or immunomodulation with tocilizumab or cyclosporine: A retrospective observational study (COQUIMA cohort).

BACKGROUND: The COVID-19 outbreak challenges the Spanish health system since March 2020. Some available therapies (antimalarials, antivirals, biological agents) were grounded on clinical case observations or basic science data. The aim of this study is to describe the characteristics and impact of different therapies on clinical outcomes in a cohort of severe COVID-19 patients. METHODS: In this retrospective, single-center, observational study, we collected sequential data on adult patients admitted to Hospital Universitario Quironsalud Madrid. Eligible patients should have a microbiological (positive test on RT-PCR assay from a nasal swab) or an epidemiological diagnosis of severe COVID-19. Demographic, baseline comorbidities, laboratory data, clinical outcomes, and treatments were compared between survivors and non-survivors. We carried out univariate and multivariate logistic regression models to assess potential risk factors for in-hospital mortality. FINDINGS: From March 10th to April 15th, 2020, 607 patients were included. Median age was 69 years [interquartile range, {IQR} 22; 65% male). The most common comorbidities were hypertension (276 [46·94%]), diabetes (95 [16·16%]), chronic cardiac (133 [22·62%]) and respiratory (114 [19·39%]) diseases. 141 patients (23·2%) died. In the multivariate model the risk of death increased with older age (odds ratio, for every year of age, 1·15, [95% CI 1·11 - 1·2]), tocilizumab therapy (2·4, [1·13 - 5·11]), C-reactive protein at admission (1·07, per 10 mg/L, [1·04 - 1·10]), d-dimer > 2·5 µg/mL (1·99, [1·03 - 3·86]), diabetes mellitus (2·61, [1·19 - 5·73]), and the PaO2/FiO2 at admission (0·99, per every 1 mmHg, [0·98 - 0·99]). Among the prescribed therapies (tocilizumab, glucocorticoids, lopinavir/ritonavir, hydroxychloroquine, cyclosporine), only cyclosporine was associated with a significant decrease in mortality (0·24, [0·12 - 0·46]; p<0·001). INTERPRETATION: In a real-clinical setting, inhibition of the calcineurin inflammatory pathway, NF-κΒ, could reduce the hyperinflammatory phase in COVID-19. Our findings might entail relevant implications for the therapy of this disease and could boost the design of new clinical trials among subjects affected by severe COVID-19. FUNDING: Hospital Universitario Quironsalud Madrid. Own fundings for COVID-19 research.

Neoadjuvant therapy and transanal endoscopic surgery in T2-T3 superficial, N0, M0 rectal tumors. Local recurrence, complete clinical and pathological response. / Neoadyuvancia y cirugía endoscópica transanal en neoplasias de recto T2-T3 superficial, N0, M0. Recidiva local, respuesta clínica y patológica completa.

INTRODUCTION: The association of preoperative chemoradiotherapy and transanal endoscopic surgery in T2 and superficial T3 rectal cancers presents promising results in selected patients. The main objective is to evaluate the long-term loco-regional and systemic recurrence and, as secondary objectives, to provide results of postoperative morbidity and the correlation between complete clinical and pathological response. METHODS: This is a retrospective observational study including a consecutive series of patients with T2-T3 superficial rectal cancer, N0, M0 who refused radical surgery (2008-2016). The treatment consisted of preoperative chemotherapy (5-fluorouracil or capecitabine) combined with radiotherapy (50, 4Gy) and transanal endoscopic surgery after 8weeks. Preoperative, surgical, pathological and long-term oncologic results were analyzed. RESULTS: Twenty-four patients were included in the study. Two of them required rescue radical surgery for unfavorable pathological results. A local recurrence (4.5%) was observed and 2patients presented systemic recurrence (9%), with a median follow-up of 45 months. A complete clinical tumor response was achieved in 12 patients (50%), and complete pathological tumor response in 9 patients (37.5%). Postoperative complications were observed in 5 patients (20.8%), and they were mild except one. There was no postoperative mortality. CONCLUSIONS: In this stage of rectal cancer, our results seem to support this strategy, mainly when a complete pathological response is achieved. The complete clinical tumor response does not coincide with the pathological tumor response. Randomized prospective studies should be performed to standardize this treatment.

Neoadyuvancia y cirugía endoscópica transanal en neoplasias de recto T2-T3 superficial, N0, M0. Recidiva local, respuesta clínica y patológica completa / Neoadjuvant therapy and transanal endoscopic surgery in T2-T3 superficial, N0, M0 rectal tumors. Local recurrence, complete clinical and pathological response

INTRODUCCIÓN: La asociación de quimiorradioterapia preoperatoria y cirugía endoscópica transanal en el cáncer rectal T2-T3 superficial presenta resultados prometedores en pacientes seleccionados. El objetivo principal es evaluar la recurrencia locorregional y sistémica a largo plazo y los objetivos secundarios son aportar resultados de morbilidad postoperatoria y la correlación entre la respuesta patológica completa y clínica completa. MÉTODOS: Estudio observacional retrospectivo de una serie consecutiva de pacientes diagnosticados de cáncer de recto T2-T3 superficial, N0, M0 que se trataron con quimiorradioterapia neoadyuvante y escisión transanal del tumor (2008-2016). Se recogieron los datos de forma prospectiva. El tratamiento consistió en quimioterapia preoperatoria (5-fluorouracilo o capecitabina) combinada con radioterapia (50,4Gy) y cirugía endoscópica transanal tras 8semanas. Se analizaron las variables preoperatorias, quirúrgicas, patológicas y los resultados oncológicos a largo plazo. RESULTADOS: De los 24 pacientes incluidos, 2requirieron rescate a cirugía radical por resultados patológicos desfavorables. Con un seguimiento mediano de 45 meses, se observó recurrencia local en un paciente (4,5%) y 2pacientes presentaron recurrencias sistémicas (9%). La respuesta clínica tumoral completa se logró en 12 pacientes (50%) y la respuesta patológica tumoral completa en 9 pacientes (37,5%). Las complicaciones postoperatorias se apreciaron en 5 pacientes (20,8%), todas leves excepto una. No hubo mortalidad postoperatoria. CONCLUSIONES: En este estadio del cáncer rectal, nuestros resultados parecen apoyar esta estrategia, principalmente cuando se logra una respuesta patológica tumoral completa. La respuesta clínica tumoral completa no coincide con la respuesta patológica tumoral. Se deben llevar a cabo estudios prospectivos aleatorizados para estandarizar este tratamiento

INTRODUCTION: The association of preoperative chemoradiotherapy and transanal endoscopic surgery in T2 and superficial T3 rectal cancers presents promising results in selected patients. The main objective is to evaluate the long-term loco-regional and systemic recurrence and, as secondary objectives, to provide results of postoperative morbidity and the correlation between complete clinical and pathological response. METHODS: This is a retrospective observational study including a consecutive series of patients with T2-T3 superficial rectal cancer, N0, M0 who refused radical surgery (2008-2016). The treatment consisted of preoperative chemotherapy (5-fluorouracil or capecitabine) combined with radiotherapy (50, 4Gy) and transanal endoscopic surgery after 8weeks. Preoperative, surgical, pathological and long-term oncologic results were analyzed. RESULTS: Twenty-four patients were included in the study. Two of them required rescue radical surgery for unfavorable pathological results. A local recurrence (4.5%) was observed and 2patients presented systemic recurrence (9%), with a median follow-up of 45 months. A complete clinical tumor response was achieved in 12 patients (50%), and complete pathological tumor response in 9 patients (37.5%). Postoperative complications were observed in 5 patients (20.8%), and they were mild except one. There was no postoperative mortality. CONCLUSIONS: In this stage of rectal cancer, our results seem to support this strategy, mainly when a complete pathological response is achieved. The complete clinical tumor response does not coincide with the pathological tumor response. Randomized prospective studies should be performed to standardize this treatment

CT diagnosis of chronic pulmonary thromboembolism.

Chronic pulmonary thromboembolism is mainly a consequence of incomplete resolution of pulmonary thromboembolism. Increased vascular resistance due to obstruction of the vascular bed leads to pulmonary hypertension. Chronic thromboembolic pulmonary hypertension is clearly more common than previously was thought, and misdiagnosis is common because patients often present with nonspecific symptoms related to pulmonary hypertension. Computed tomography (CT) is a useful alternative to conventional angiography not only for diagnosing chronic pulmonary thromboembolism but also for determining which cases are treatable with surgery and confirming technical success postoperatively. The vascular CT signs include direct pulmonary artery signs (complete obstruction, partial obstruction, eccentric thrombus, calcified thrombus, bands, webs, poststenotic dilatation), signs related to pulmonary hypertension (enlargement of main pulmonary arteries, atherosclerotic calcification, tortuous vessels, right ventricular enlargement, hypertrophy), and signs of systemic collateral supply (enlargement of bronchial and nonbronchial systemic arteries). The parenchymal signs include scars, a mosaic perfusion pattern, focal ground-glass opacities, and bronchial anomalies. The presence of one or more of these radiologic signs arouses suspicion and allows diagnosis of this entity. Early recognition of chronic pulmonary thromboembolism may help improve the outcome, since the condition is potentially curable with pulmonary thromboendarterectomy.

Voiding urosonography: the study of the urethra is no longer a limitation of the technique.

BACKGROUND: Voiding urosonography (VUS) has proved to be a reliable method for the study of vesicoureteric reflux (VUR). Early reports considered it inadequate for imaging the male urethra. OBJECTIVE: To determine the usefulness of contrast-enhanced VUS for the study of the urethra. MATERIAL AND METHODS: A total of 208 children aged 2 days to 10 years underwent VUS to confirm or exclude VUR for different reasons (n = 150) or for follow-up (n = 58). Patients with unconfirmed suspicion of VUR (99 boys and 51 girls) also underwent VUS for the study of the urethra. Examinations were performed using a harmonic imaging mode specific for contrast (Levovist) enhancement. We used a 6-4-MHz convex probe and a transperineal and/or a transpelvic approach. RESULTS: The neck of the bladder and the entire urethra were visualized in all patients (n = 150). The male urethra was considered normal in 95 boys (95.95%). We diagnosed posterior urethral valves in two patients, diverticulum of the prostatic utricle in one, and diverticulum of the anterior urethra in one. All abnormal cases were confirmed using conventional voiding cystourethrography. CONCLUSION: VUS can replace voiding cystourethrography as the method of choice for the initial study of suspected VUR in children.

Chemotherapy-induced nausea and vomiting in acute leukemia and stem cell transplant patients: results of a multicenter, observational study.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the incidence and severity of chemotherapy-induced nausea and vomiting (CINV) in oncohematology in routine clinical practice, its impact on quality of life, and caregivers' perception of the extent of the problem. DESIGN AND METHODS: This was a multicenter, prospective, observational follow-up study including: (i) acute myeloid leukemia patients treated with moderately to highly emetogenic chemotherapy and (ii) hematopoietic stem cell transplant recipients, without reduced intensity conditioning. No exclusion criteria were applied. All patients received at least one 5-HT3 antagonist for emesis prophylaxis. Patients recorded emetic episodes and rated nausea daily. Quality of life was assessed through a validated functional living Index-Emesis questionnaire. A survey of caregivers' predictions of CINV was made and the predictions then compared with the observed CINV. RESULTS: One hundred consecutive transplant and 77 acute myeloid leukemia patients were studied. Transplant conditioning was the most important risk factor for CINV: complete response occurred in only 20% of transplant patients (vs. 47% for leukemia patients). Among patients with emesis, the mean percentage of days with emesis and the mean (+/-SD) total number of emetic episodes were 61% and 9.4+/-8.9 (transplant recipients), and 53.6% and 6.2+/-7.3 (leukemia patients), respectively. CINV control was lower in the delayed than in the acute phase. Antiemetic rescue therapy was ineffective. CINV had a deleterious effect on quality of life, especially among transplant recipients. Caregivers underestimated the incidence of delayed nausea and emesis in the transplant setting. INTERPRETATION AND CONCLUSIONS: Despite 5-HT3 antagonist prophylaxis, CINV remains a significant problem in oncohematology, especially in the delayed phase and in transplant recipients.