Effect of Tocilizumab vs Standard Care on Clinical Worsening in Patients Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial.

Importance: The coronavirus disease 2019 (COVID-19) pandemic is threatening billions of people worldwide. Tocilizumab has shown promising results in retrospective studies in patients with COVID-19 pneumonia with a good safety profile. Objective: To evaluate the effect of early tocilizumab administration vs standard therapy in preventing clinical worsening in patients hospitalized with COVID-19 pneumonia. Design, Setting, and Participants: Prospective, open-label, randomized clinical trial that randomized patients hospitalized between March 31 and June 11, 2020, with COVID-19 pneumonia to receive tocilizumab or standard of care in 24 hospitals in Italy. Cases of COVID-19 were confirmed by polymerase chain reaction method with nasopharyngeal swab. Eligibility criteria included COVID-19 pneumonia documented by radiologic imaging, partial pressure of arterial oxygen to fraction of inspired oxygen (Pao2/Fio2) ratio between 200 and 300 mm Hg, and an inflammatory phenotype defined by fever and elevated C-reactive protein. Interventions: Patients in the experimental arm received intravenous tocilizumab within 8 hours from randomization (8 mg/kg up to a maximum of 800 mg), followed by a second dose after 12 hours. Patients in the control arm received supportive care following the protocols of each clinical center until clinical worsening and then could receive tocilizumab as a rescue therapy. Main Outcome and Measures: The primary composite outcome was defined as entry into the intensive care unit with invasive mechanical ventilation, death from all causes, or clinical aggravation documented by the finding of a Pao2/Fio2 ratio less than 150 mm Hg, whichever came first. Results: A total of 126 patients were randomized (60 to the tocilizumab group; 66 to the control group). The median (interquartile range) age was 60.0 (53.0-72.0) years, and the majority of patients were male (77 of 126, 61.1%). Three patients withdrew from the study, leaving 123 patients available for the intention-to-treat analyses. Seventeen patients of 60 (28.3%) in the tocilizumab arm and 17 of 63 (27.0%) in the standard care group showed clinical worsening within 14 days since randomization (rate ratio, 1.05; 95% CI, 0.59-1.86). Two patients in the experimental group and 1 in the control group died before 30 days from randomization, and 6 and 5 patients were intubated in the 2 groups, respectively. The trial was prematurely interrupted after an interim analysis for futility. Conclusions and Relevance: In this randomized clinical trial of hospitalized adult patients with COVID-19 pneumonia and Pao2/Fio2 ratio between 200 and 300 mm Hg who received tocilizumab, no benefit on disease progression was observed compared with standard care. Further blinded, placebo-controlled randomized clinical trials are needed to confirm the results and to evaluate possible applications of tocilizumab in different stages of the disease. Trial Registration: ClinicalTrials.gov Identifier: NCT04346355; EudraCT Identifier: 2020-001386-37.

Pulmonary Sarcoidosis Presenting with Miliary Opacities.

BACKGROUND: Lung lesions often appear in patients with sarcoidosis; however, miliary opacities are rare. We present the case of a 55-year-old Indian man who presented with dyspnea and low-grade fever. DISCUSSION: Miliary Tuberculosis (TB) was initially suspected, despite the direct microscopic examination from bronchoalveolar lavage was negative for acid-fast bacilli because imaging showed miliary opacities, and transbronchial lung biopsy revealed the presence of typical caseating granulomas. Antitubercular treatment with the classic four-drug regimen was initiated. However, the patient did not improve and cultures were negative for Mycobacterium growth. The diagnosis of sarcoidosis was made only after a negative culture and clinical and histopathological re-evaluation of the case. CONCLUSION: Although miliary sarcoidosis is rare, physicians should consider sarcoidosis in the differential diagnosis with conditions like tuberculosis, malignancy, and pneumoconiosis when patients present with miliary opacities who do not respond to the traditional treatment.

Magnetic resonance-guided focused ultrasound for the treatment of painful bone metastases: role of apparent diffusion coefficient (ADC) and dynamic contrast enhanced (DCE) MRI in the assessment of clinical outcome.

PURPOSE: To assess the correlation between functional MRI, including ADC values obtained from DWI and DCE, and clinical outcome in patients with bone metastases treated with MRgFUS. METHODS AND MATERIALS: Twenty-three patients with symptomatic bone metastases underwent MRgFUS treatment (ExAblate 2100 system InSightec) for pain palliation. All patients underwent clinical and imaging follow-up examinations at 1, 3 and 6 months after treatment. Visual Analog Scale (VAS) score was used to evaluate treatment efficacy in terms of pain palliation while ADC maps obtained by DWI sequences, and DCE data were used for quantitative assessment of treatment response at imaging. Spearman Correlation Coefficient Test was calculated to assess the correlation between VAS, ADC and DCE data. RESULTS: All treatments were performed successfully without adverse events. On the basis of VAS score, 16 (69.6 %) patients were classified as complete clinical responders, 6 (26.1 %) as partial responders and only one (4.3 %) was classified as a non-responder. The mean VAS score decreased from 7.09 ± 1.8 at baseline to 2.65 ± 1.36 at 1 month, 1.04 ± 1.91 at 3 months and 1.09 ± 1.99 at 6 months (p < 0.001). Baseline mean ADC value of treated lesions was 1.05 ± 0.15 mm2/s, increasing along follow-up period (1.57 ± 0.27 mm2/s 1st month; 1.49 ± 0.3 mm2/s 3rd month; 1.45 ± 0.32 mm2/s 6th month, p < 0.001). Non perfused volume (NPV) was 46.4 at 1 month, 45.2 at 3 months and 43.8 at 6 months. Spearman Coefficient demonstrated a statistically significant negative correlation between VAS and ADC values (ρ = -0.684; p = 0.03), but no significant correlation between VAS and NPV (ρ = 0.02216, p = 0.9305). Among other DCE data, Ktrans significantly changed in complete responders (3 months Ktrans = 2.14/min; -ΔKt = 52.65 % p < 0.01) and was not significantly different in partial responders (3 months Ktrans 0.042/min; ΔKt = 11.39 % p > 0.01). CONCLUSION: In patients with painful bone metastases treated with MRgFUS, ADC and Ktrans variation observed in the ablated lesions correlate with VAS values and may play a role as objective imaging marker of treatment response.

Preliminary clinical experience with a dedicated interventional robotic system for CT-guided biopsies of lung lesions: a comparison with the conventional manual technique.

OBJECTIVE: Evaluate the performance of a robotic system for CT-guided lung biopsy in comparison to the conventional manual technique. MATERIALS AND METHODS: One hundred patients referred for CT-guided lung biopsy were randomly assigned to group A (robot-assisted procedure) or group B (conventional procedure). Size, distance from entry point and position in lung of target lesions were evaluated to assess homogeneity differences between the two groups. Procedure duration, dose length product (DLP), precision of needle positioning, diagnostic performance of the biopsy and rate of complications were evaluated to assess the clinical performance of the robotic system as compared to the conventional technique. RESULTS: All biopsies were successfully performed. The size (p = 0.41), distance from entry point (p = 0.86) and position in lung (p = 0.32) of target lesions were similar in both groups (p = 0.05). Procedure duration and radiation dose were significantly reduced in group A as compared to group B (p = 0.001). Precision of needle positioning, diagnostic performance of the biopsy and rate of complications were similar in both groups (p = 0.05). CONCLUSION: Robot-assisted CT-guided lung biopsy can be performed safely and with high diagnostic accuracy, reducing procedure duration and radiation dose in comparison to the conventional manual technique. KEY POINTS: • CT-guided biopsy is the main procedure to obtain diagnosis in lung tumours. • The robotic device facilitates percutaneous needle placement under CT guidance. • Robot-assisted CT-guided lung biopsy reduces procedure duration and radiation dose.

MR imaging-guided focused ultrasound for treatment of bone metastasis.

Magnetic resonance (MR) imaging-guided focused ultrasound is an alternative noninvasive method for reducing the pain in skeletal metastases. MR imaging-guided focused ultrasound ablation offers several key advantages over other noninvasive treatment modalities. This technology enables the performance of three-dimensional treatment planning with MR imaging and continuous temperature mapping of treated tissue by using MR thermometry, thereby enabling real-time monitoring of thermal damage in the target zone. The concentration of acoustic energy on the intact surface of cortical bone produces a rapid temperature increase that mediates critical thermal damage to the adjacent periosteum, the most innervated component of mature bone tissue. Such thermal ablation has been shown to be an extremely effective approach for pain management. Energy delivered during MR imaging-guided focused ultrasound ablation and accumulated inside the pathologic soft tissue of the metastases can create a variable amount of tissue necrosis. This technique has also a potential role in achieving local tumor control, allowing remineralization of trabecular bone or reduction in lesion size. The current report presents a detailed step-by-step guide for performing MR imaging-guided focused ultrasound ablation of bone metastases, including use of MR thermometry for monitoring treatment, protocol selection for simple palliation of pain or for local tumor control, and a description of imaging features of periosteal neurolysis or metastasis ablation. Two case studies are also presented: in the first, the technique provided palliation of pain in bone metastases, and in the second, the technique achieved tumor control as further proof of primary efficacy. MR imaging-guided focused ultrasound ablation is a promising method for successful palliation of bone metastasis pain and tumor control, because of the bony structure remodeling induced by thermo-related coagulative necrosis.

MR-guided high-intensity focused ultrasound: current status of an emerging technology.

The concept of ideal tumor surgery is to remove the neoplastic tissue without damaging adjacent normal structures. High-intensity focused ultrasound (HIFU) was developed in the 1940s as a viable thermal tissue ablation approach. In clinical practice, HIFU has been applied to treat a variety of solid benign and malignant lesions, including pancreas, liver, prostate, and breast carcinomas, soft tissue sarcomas, and uterine fibroids. More recently, magnetic resonance guidance has been applied for treatment monitoring during focused ultrasound procedures (magnetic resonance-guided focused ultrasound, MRgFUS). Intraoperative magnetic resonance imaging provides the best possible tumor extension and dynamic control of energy deposition using real-time magnetic resonance imaging thermometry. We introduce the fundamental principles and clinical indications of the MRgFUS technique; we also report different treatment options and personal outcomes.

Persistence of the sciatic artery: a case report of a combined (complete and incomplete) type causing leg ischemia.

Persistent sciatic artery is a very uncommon embryologic vascular variant, with a prevalence of 0.05% based on angiographic studies. Two different types of this anomaly can occur, complete or incomplete, on the basis of the relationship between sciatic artery and femoral artery. Although many of these patients are asymptomatic, it may represent a threat to the viability of the lower extremity because of atherosclerotic degeneration resulting in aneurysmal dilatation, occlusive thrombosis, or embolic phenomena with distal complication. We present a case of a 64-year-old man with combined, complete and incomplete, type of persistent sciatic artery causing ischemic ulcer of the first toe.

Oxaliplatin in combination with 5-fluorouracil (5-FU) and leucovorin (LV) in patients with metastatic gastric cancer (MGC).

OBJECTIVE: Treatment options for advanced or metastatic gastric cancer (A/MGC) are limited and inclusion of novel substances is necessary. Few studies have confirmed the activity and tolerability of the combination of oxaliplatin (OXA) and 5-fluorouracil (5-FU) modulated with leucovorin (LV) administrated to patients with A/MGC. The goal of current study was to evaluate the efficacy and toxicity of Folfox-4 regimen in patients with A/MGC. PATIENTS AND METHODS: Fifty-six patients were treated with Folfox-4 regimen. Treatment was continued until disease progression, unacceptable toxicity or until a patient chose to discontinue treatment. Responses to treatment and toxicity were recorded according to the WHO criteria and NCI toxicity criteria. RESULTS: All patients were assessable for toxicity and response. Patients (71.4% male, 28.6% female) had a median age of 65 years (range, 28-78). All patients had histologically confirmed metastatic (89.3%) or advanced (10.7%) gastric cancer. Response was evaluated every 6 weeks; 1 complete (1.8%) and 23 (41.1%) partial remission were observed (overall response rate 42.9%). Twenty patients (35.7%) showed stable disease and 12 (21.4%) had a progressive disease. Median overall survival, time to progression and follow up were 10 months, 6 months, and 11.5 months, respectively. WHO grade 3 or 4 hematologic toxicities included leucopenia, neutropenia, thrombocytopenia, and anemia. No patient experienced neutropenic fever. Other grade 3/4 toxicities included nausea, vomiting, diarrhea, stomatitis, and anorexia. Three patients (5.3%) experienced grade 3 peripheral neuropathy. No treatment-related deaths were recorded. CONCLUSIONS: Folfox-4 regimen is active and well tolerated in patients with advanced/metastatic gastric cancer.

Multiresistant-MRSA tricuspid valve infective endocarditis with ancient osteomyelitis locus.

BACKGROUND: Methicillin-resistant S. aureus (MRSA) with low susceptibility to glycopeptides is uncommon. CASE PRESENTATION: The case of a 50-year-old non-drug addict patient presenting with tricuspid valve infective endocarditis (IE) by MRSA resistant to vancomycin and linezolid is presented. There was response only to quinupristin/dalfopristin. He had a motorcycling accident four years before undergoing right above-the-knee amputation and orthopaedic fixation of the left limb. There were multiple episodes of left MRSA-osteomyelitis controlled after surgery and vancomycin therapy. MRSA isolated from the blood at the time of IE presented with the same profile than the isolated four years earlier. Sequential treatment with teicoplanin-cotrimoxazole and Linezolid associated to vancomycin--rifampicin--cotrimoxazole had no improvement. Infection was controlled after 28 days of therapy with quinupristin/dalfopristin. CONCLUSION: The literature presents only a few cases of MRSA IE not susceptible to glycopeptides in not drug addicted patients. This case shows the comparison of a highly-resistant MRSA after previous S. aureus osteomyelitis treated with glycopeptides. This is the first description of successful treatment of resistant-MRSA IE of the tricuspid valve complicated by multiple pulmonary septic infarction with quinupristin/dalfopristin.