Ex-vivo mucolytic and anti-inflammatory activity of BromAc in tracheal aspirates from COVID-19.

COVID-19 is a lethal disease caused by the pandemic SARS-CoV-2, which continues to be a public health threat. COVID-19 is principally a respiratory disease and is often associated with sputum retention and cytokine storm, for which there are limited therapeutic options. In this regard, we evaluated the use of BromAc®, a combination of Bromelain and Acetylcysteine (NAC). Both drugs present mucolytic effect and have been studied to treat COVID-19. Therefore, we sought to examine the mucolytic and anti-inflammatory effect of BromAc® in tracheal aspirate samples from critically ill COVID-19 patients requiring mechanical ventilation. METHOD: Tracheal aspirate samples from COVID-19 patients were collected following next of kin consent and mucolysis, rheometry and cytokine analysis using Luminex kit was performed. RESULTS: BromAc® displayed a robust mucolytic effect in a dose dependent manner on COVID-19 sputum ex vivo. BromAc® showed anti-inflammatory activity, reducing the action of cytokine storm, chemokines including MIP-1alpha, CXCL8, MIP-1b, MCP-1 and IP-10, and regulatory cytokines IL-5, IL-10, IL-13 IL-1Ra and total reduction for IL-9 compared to NAC alone and control. BromAc® acted on IL-6, demonstrating a reduction in G-CSF and VEGF-D at concentrations of 125 and 250 µg. CONCLUSION: These results indicate robust mucolytic and anti-inflammatory effect of BromAc® ex vivo in tracheal aspirates from critically ill COVID-19 patients, indicating its potential to be further assessed as pharmacological treatment for COVID-19.

Preclinical validation of occupational and environmental safety of an isolation system for noninvasive ventilation in COVID-19 and other aerosol-transmitted infections.

Background: The current SARS-CoV-2 pandemic has provoked the collapse of some health systems due to insufficient intensive care unit capacity. The use of continuous positive airway pressure (CPAP) and high-flow nasal oxygen (HFNO) therapies has been limited in consideration of the risk of occupational infection in health-care professionals. Aims: In preclinical experimental simulations, evaluate occupational and environmental safety of the newly developed isolation system for aerosol-transmitted infections (ISATI). Method: Simulations were conducted to test ISATI's capability to isolate aerosolized molecular (caffeine), and biological (SARS-CoV-2 synthetic RNA) markers. Caffeine deposition was analyzed on nitrocellulose sensor discs by proton nuclear magnetic resonance spectroscopy. Synthetic SARS-CoV-2 detection was performed by reverse transcription-polymerase chain reaction. Results: ISATI demonstrated efficacy in isolating molecular and biological markers within the enclosed environment in simulated conditions of CPAP, HFNO and mechanical ventilation therapy. Neither the molecular marker nor substantial amounts of synthetic SARS-CoV-2 RNA were detected in the surrounding environment, outside ISATI, indicating appropriate occupational safety for health-care professionals. Conclusion: Aerosolized markers were successfully contained within ISATI in all experimental simulations, offering occupational and environmental protection against the dissemination of aerosolized microparticles under CPAP or HFNO therapy conditions, which are indicated for patients with acute respiratory infections.

Metastases to retroperitoneal or lateral pelvic lymph nodes indicated unfavorable survival and high pelvic recurrence rates in a cohort of 102 patients with low rectal adenocarcinoma.

BACKGROUND AND OBJECTIVES: The Japanese protocol considers metastases to retroperitoneal or lateral pelvic lymph nodes (RLPNs) as regional lymphatic dissemination in rectal adenocarcinoma patients and recommends total mesorectal excision (TME) plus retroperitoneal and lateral pelvic lymphadenectomy (RLPL). Western protocols consider RLPN metastases to indicate advanced disease. METHODS: All outcomes were evaluated among a cohort of 102 rectal adenocarcinoma patients subjected to TME plus RLPL with a nerve-preserving technique. Chemoradiotherapy was delivered in patients with T3/T4 tumors or metastases to mesorectal nodes or RLPNs. RESULTS: Surgical mortality was 3.9%; surgical morbidity was 33.3%. Incidence of RLPN metastases was 17%. Pelvic recurrence was 14.5% in pT3/pT4 patients and 29.4% in patients with metastases to RLPNs. Survival at 50 months was 28.6% in patients with RLPN metastases versus 84.5% in patients without RLPN metastases (P < 0.0001). Survival at 50 months was 33.3% in TME stage II patients with RLPN metastases versus 97.1% in TME stage II patients without RLPN metastases (P < 0.0001), and 21.9% in TME stage III patients with RLPN metastases versus 68.9% in TME stage III patients without RLPN metastases (P = 0.0237). CONCLUSIONS: Patients who underwent RLPL had acceptable morbidity and mortality rates. Metastases to RLPNs indicated unfavorable survival and considerable pelvic recurrence rates.

Retroperitoneal and lateral pelvic lymphadenectomy mapped by lymphoscintigraphy for rectal adenocarcinoma staging.

BACKGROUND: The good prognosis of retroperitoneal and lateral pelvic lymphadenectomy has raised the question of whether total mesorectal excision is suitable for adequate staging of rectal adenocarcinoma patients. The aims of this study were to determine the accuracy of dye and probe detection of metastatic retroperitoneal and/or lateral pelvic nodes and to define the upstaging impact of retroperitoneal and lateral pelvic lymphadenectomy in rectal adenocarcinoma patients. METHODS: Ninety-seven rectal adenocarcinoma patients were submitted to total mesorectal excision and retroperitoneal and lateral pelvic lymphadenectomy. Lymphoscintigraphy using technetium-99 m-phytate and patent blue was performed to detect blue and/or radioactive retroperitoneal and/or lateral pelvic nodes which were examined histopathologically and immunohistochemically with a step-sectioning technique. RESULTS: Mesorectal mean node count was 11.5 and retroperitoneal and/or lateral pelvic node was 11.7. Retroperitoneal and lateral pelvic lymphadenectomy identified metastases in 17.5%, upstaging 8.2%. Variables related to metastatic retroperitoneal and/or lateral pelvic nodes were the following: Stage III in total mesorectal excision specimens (P < 0.04), pT3/pT4 tumors (P = 0.047), high levels of carcinoembryonic antigen (P = 0.014) and large tumors (P = 0.03). Marker migration to retroperitoneal and/or lateral pelvic nodes occurred in 37.1%, upstaging 11.1%. The markers' accuracy in the detection of metastatic retroperitoneal and/or lateral pelvic nodes was 100%. CONCLUSIONS: Retroperitoneal and lateral pelvic lymphadenectomy detected an important rate of metastatic retroperitoneal and/or lateral pelvic nodes (RLPN), resulting in upstaging. When markers migrated, they were able to detect RLPN metastases. The use of markers should be improved in the identification of RLPN metastases for selective indication of retroperitoneal and lateral pelvic lymphadenectomy.

Upstaging benefits and accuracy of sentinel lymph node mapping in colorectal adenocarcinoma nodal staging.

BACKGROUND AND OBJECTIVES: Sentinel lymph node (SLN) mapping is an additional method for improving colorectal cancer nodal staging. The purpose of the study was to define the method's accuracy in nodal staging, its upstaging benefits and to identify the predictive factors for its failure. METHODS: Lymphatic mapping was performed using technetium-99m-phytate and patent blue in 52 consecutive colorectal adenocarcinoma patients. Enhanced pathological examination was carried out on SLNs with hematoxylin-eosin step-sectioning and immunochemistry. RESULTS: The patients studied had an average tumor size of 6.5 cm; 85% had T3/T4 tumors; and rectal tumors represented 57.7% of the group. Overall SLN mapping accuracy was 79.5%, with sensitivity of 65.2% and 34.8% false negatives. Upstaging with SLN mapping was 23.1%. Colon tumors had an SLN identification rate of 90.9% and rectal tumors had 63.3% (P = 0.023). Multivariate statistical analysis identified lower rectal tumor (P = 0.009), neoadjuvant treatment (P = 0.029) and tumor size (P = 0.036) as independent risk factors for the inability to detect SLNs. CONCLUSIONS: Upstaging benefits of SLN mapping should be considered in colon and mid- and upper rectal tumors. The method should be avoided in patients with lower rectal tumors, large tumors and having had neoadjuvant therapy.

Retroperitoneal and lateral pelvic lymphadenectomy mapped by lymphoscintigraphy and blue dye for rectal adenocarcinoma staging: preliminary results.

BACKGROUND: Total mesorectal excision (TME) is the standard surgical choice for rectal adenocarcinoma. Better prognostic results, achieved with a retroperitoneal and lateral pelvic lymphadenectomy (RLPL), have questioned that TME might not be satisfactory for adequate patient staging, affecting therapeutic definitions. The aims of the ongoing study are to define the accuracy of dye and probe search in the detection of metastatic retroperitoneal and lateral pelvic nodes (RLPN) resected with RLPL, and to evaluate the metastasis frequency in these nodes and its eventual upstaging impact. METHODS: Thirty rectal adenocarcinoma patients were submitted to RLPL, with RLPN mapping using technetium (Tc 99 m) and patent blue, having nodes examined histopathologically and immunohistochemically. RESULTS: Eight hundred and two nodes were analyzed, mean of 26.7 per patient; RLPL was responsible for 41% (330) of the examined nodes, mean of 11 per patient. Metastatic RLPN have occurred in 20% of the patients; the RLPN were metastatic in only 6.7% of the patients; RLPL upstaged 13.3%. For identification of metastatic RLPN with technetium, sensitivity was 33%, specificity 79%, positive predictor value (PPV) 29%, negative predictor value (NPV) 83% and false negative (FN) rate 67%. For patent blue and technetium metastatic RLPN identification, sensitivity was 17%, specificity 92%, PPV 33%, NPV 82% and FN 83%. CONCLUSIONS: Preliminary results have pointed out technetium and blue dye low accuracy to identify metastatic RLPN; no metastatic RLPN were reported in the patients submitted to preoperative chemoradiation and important upstaging with RLPL. Considering no increase in morbi-mortality rates with RLPL, definitive conclusions will be obtained as the study carries on.

Good outcome after neoadjuvant chemotherapy and extended surgical resection for a large radiation-induced high-grade breast sarcoma.

This article is a case report of a high grade, radio-induced, breast malignant fibrous histiocytoma (undifferentiated high grade pleomorphic sarcoma), which developed in a 44-year old female, seven years after breast conservative surgery and radiotherapy for a T1N0M0 invasive left breast ductal carcinoma. The sarcoma presented as a fast growing tumour, 9.5 cm in the largest diameter, with skin, left breast, chest wall muscle and rib invasion. Neoadjuvant chemotherapy was performed with epirubicin and ifosfamide. Extended radical surgery according to oncological standards and soft tissue reconstruction were carried out. Despite bad prognostic features of high grade and large invasive sarcoma, the patient is currently, after 44 months of follow up, without local recurrence, or metastases, exceeding the 12.8-month mean recurrence period and mortality rate for these tumours larger than 8.1 cm (+/- 1.2 cm) as described in the literature.