Surgical treatment of lung cancer with adjacent lobe invasion in relation to fissure integrity

Background Tumor with adjacent lobe invasion (T‐ALI) is an uncommon condition. Controversy still exists regarding the optimal resection of adjacent lobe invasion, and the prognostic value in relation to fissure integrity at the tumor invasion point. The aims of this paper were to evaluate the prognosis of T‐ALI with regard to fissure integrity, and type of resection. Methods This was a retrospective multicenter study which included all consecutive patients with T‐ALI undergoing surgical treatment. Based on radiological, intraoperative and histological findings, T‐ALI patients were differentiated into two groups based on whether the fissure was complete (T‐ALI‐A group) or incomplete (T‐ALI‐D Group) at the level of tumor invasion point. Clinico‐pathological features and survival of two study groups were analyzed and compared. Results Study population included 135 patients, of these 98 (72%) were included into T‐ALI‐A group, and 37 (38%) into T‐ALI‐D Group. T‐ALI‐D patients had better overall survival than T‐ALI‐A patients (63.9 ± 7.0 vs. 48.9 ± 3.9; respectively, P = 0.01) who presented with a higher incidence of lymph node involvement (35% vs. 4%; P = 0.004), and recurrence rate (43% vs. 16%; P = 0.01). At multivariable analysis, T‐ALI‐D (P = 0.01), pN0 stage (P = 0.0002), and pT≤5 cm (P = 0.0001) were favorable survival prognostic factors. Conclusions T‐ALI‐D presented a better prognosis than T‐ALI‐A while extent of resection had no effect on survival. Thus, in patients with small T‐ALI‐D and without lymph node involvement, sublobar resection of adjacent lobe rather than lobectomy could be indicated. Key points The extent of resection of adjacent lobe had no effect on survival while T‐ALI‐D, pN0 stage, and pT≤5 cm were significant prognostic factors. In patients with small T‐ALI‐D and without lymph node involvement, sublobar resection of adjacent lobe could be indicated as an alternative to lobectomy

protective effect of a new hyaluronic acid carnosine conjugate on the modulation of the inflammatory response in mice subjected to collagen induced arthritis

Abstract Several studies demonstrated the pharmacological actions of carnosine as well as hyaluronic acid (HA) during joint inflammation. In that regard, the aim of this study was to investigate the protective effect of a new HA -Carnosine conjugate (FidHycarn) on the modulation of the inflammatory response in mice subjected to collagen-induced arthritis (CIA). CIA was induced by two intradermal injections of 100 μl of an emulsion of collagen (CII) and complete Freund's adjuvant (CFA) at the base of the tail on day 0 and 21. At 35 day post CIA induction, the animals were sacrificed. CII injection caused erythema and edema in the hind paws, histological alterations with erosion of the joint cartilage as well as behavioral changes. Oral treatment with FidHycarn starting at the onset of arthritis (day 25) ameliorated the clinical signs, improved behavioral deficits as well as decreased histological and radiographic alterations. The degree of oxidative damage evaluated by inducible nitric oxide synthase (iNOS), nitrotyrosine, poly-ADP-ribose (PAR) expressions and malondialdehyde (MDA) levels, was also significantly reduced in Carnosine+HA association and FidHycarn treated mice. Moreover, the levels of proinflammatory cytokines and chemokines and cyclo-oxygenase COX-2 enzyme were also more significantly reduced by Carnosine+HA and FidHycarn compared to carnosine alone. However, interestingly, in some cases, the effects of FidHycarn were more important than Carnosine+HA association and not statistically different to methotrexate (MTX) used as positive control. Thus, the conjugation of Carnosine with HA (FidHycarn) could represent an interesting therapeutic strategy to combat arthritis disorders

Circulating mitochondrial DNA is an early indicator of severe illness and mortality from COVID-19

BackgroundMitochondrial DNA (MT-DNA) are intrinsically inflammatory nucleic acids released by damaged solid organs. Whether circulating cell-free MT-DNA quantitation could be used to predict the risk of poor COVID-19 outcomes remains undetermined.MethodsWe measured circulating MT-DNA levels in prospectively collected, cell-free plasma samples from 97 subjects with COVID-19 at hospital presentation. Our primary outcome was mortality. Intensive care unit (ICU) admission, intubation, vasopressor, and renal replacement therapy requirements were secondary outcomes. Multivariate regression analysis determined whether MT-DNA levels were independent of other reported COVID-19 risk factors. Receiver operating characteristic and area under the curve assessments were used to compare MT-DNA levels with established and emerging inflammatory markers of COVID-19.ResultsCirculating MT-DNA levels were highly elevated in patients who eventually died or required ICU admission, intubation, vasopressor use, or renal replacement therapy. Multivariate regression revealed that high circulating MT-DNA was an independent risk factor for these outcomes after adjusting for age, sex, and comorbidities. We also found that circulating MT-DNA levels had a similar or superior area under the curve when compared against clinically established measures of inflammation and emerging markers currently of interest as investigational targets for COVID-19 therapy.ConclusionThese results show that high circulating MT-DNA levels are a potential early indicator for poor COVID-19 outcomes.FundingWashington University Institute of Clinical Translational Sciences COVID-19 Research Program and Washington University Institute of Clinical Translational Sciences (ICTS) NIH grant UL1TR002345

Anorectal melanoma: a rare aggressive type of melanoma

First described in 1857, anorectal melanoma (AM) is an extremely rare cancer comprising approximately 1% of all anorectal malignancies and cutaneous melanomas. Different from cutaneous melanoma which has a strong association with ultraviolet radiations and a preference for young Caucasians, AM is equally distributed among human races reaching a peak incidence in the eighth decade of life (50%); however, its incidence is increasing in young human immunodeficiency virus and human papillomavirus patients, suggesting a role of immunology for its development

Bilateral ultrasound-guided erector spinae plane block for pectus excavatum surgery: a retrospective propensity-score study

Objective: Pectus excavatum (PE) repair is burdened by severe postoperative pain. This retrospective study aimed to determine whether the analgesic effect of ultrasound-guided erector spinae plane block (ESPB) plus standard intravenous analgesia (SIVA) might be superior to SIVA alone in pain control after PE surgical repair via Ravitch or Nuss technique. Design: A retrospective cohort study. Setting: At a university hospital. Participants: All participants were scheduled for surgical repair of PE. Interventions: From January 2017 to December 2019, all patients who received ESPB plus SIVA or SIVA alone were investigated retrospectively. A 2:1 propensity-score matching analysis considering preoperative variables was used to compare analgesia efficacy in 2 groups. All patients received a 24-hour continuous infusion of tramadol, 0.1 mg/kg/h, and ketorolac, 0.05 mg/kg/h, via elastomeric pump, and morphine, 2 mg, intravenously as a rescue drug. The ESPB group received preoperative bilateral ESPB block. Postoperative pain, reported using a numerical rating scale at 1, 12, 24, and 48 hours after surgery; the number of required rescue doses; total postoperative morphine milligram equivalents consumption; and the incidence of postoperative nausea and vomit were analyzed. Measurement and main results: A total of 105 patients were identified for analysis. Propensity-score matching resulted in 38 patients in the SIVA group and 19 patients in the ESPB group. Postoperative pain, the number of rescue doses, and postoperative nausea and vomit incidences were lower in the ESPB group (p < 0.005). Conclusions: Erector spinae plane block may be an effective option for pain management after surgical repair of PE as part of a multimodal approach. This study showed good perioperative analgesia, opioid sparing, and reduced opioid-related adverse effects

Subxifoid versus transthoracic thoracoscopic lobectomy: Results of a retrospective analysis before and after matching analysis

Background Here, we report our initial experience with subxifoid video-assisted thoracoscopic surgery (SVATS) lobectomy for the management of primary lung cancer, and compared the outcomes of SVATS with those of conventional transthoracic VATS (CVATS) lobectomies to validate its feasibility and usefulness.Methods The clinical data of consecutive patients undergoing VATS lobectomy via SVATS or CVATS for lung cancer were retrospectively compared. The endpoints were to evaluate the statistical differences in surgical results, postoperative pain (measured with visual analog scale [VAS] scores at 8 hours, Day 1, Day 2, Day 3, at discharge, one month and three months after surgery) and paresthesia (measured at one- month, and three months after surgery). The two groups were compared before and after matching analysis.Results Our study population included 223 patients: 84 in the SVATS and 139 in the CVATS group. The two groups were not comparable for sex (P = 0.001), preoperative comorbidity as cardiopathy (P = 0.007), BMI value (P = 0.003), left-sided procedure (P = 0.04), tumor stage (P = 0.04), and tumor size (P = 0.002). These differences were overcome by propensity score matching (PSM) analysis that yielded two well-matched groups which included 61 patients in each group. Surgical outcomes including blood loss, hospital stay and complications were similar before and after matching analysis, but SVATS compared to CVATS was associated with longer operative time before (159 +/- 13 vs. 126 +/- 6.3, P < 0.0001), and after matching analysis (161 +/- 23 vs. 119 +/- 8.3; P < 0.0001) and significant reduction of postoperative pain during the different time-points (P < 0.001), and paresthesia at one (P = 0.001), and three months (P < 0.0001).Conclusions SVATS lobectomy is a feasible and safe strategy with surgical outcomes similar to CVATS lobectomy but with less postoperative pain and paresthesia.Key pointsSignificant findings of the studySubxifoid thoracoscopic lobectomy is a feasible and safe procedure, with potential benefits in terms of postoperative pain and paresthesia compared to conventional thoracoscopic lobectomyOur results showed that surgical outcomes including blood loss, hospital stay, morbidity and mortality are similar but subxifoid thoracoscopy was associated with significant reduction of postoperative pain and paresthesia.What this study addsSubxifoid thoracoscopy is a safe procedure; compared to conventional transthoracic thoracoscopy, it avoids intercostal incisions, and spares nerve trauma, resulting in a reduction of postoperative pain and paresthesia

Palmitoylethanolamide Supplementation during Sensitization Prevents Airway Allergic Symptoms in the Mouse

One important risk factor for the development of asthma is allergen sensitization. Recent increasing evidence suggests a prominent role of mast cells in asthma pathophysiology. Since Palmitoylethanolamide (PEA), an endogenous lipid mediator chemically related to – and co-released with- the endocannabinoid anandamide, behaves as a local autacoid down-regulator of mast cell activation and inflammation, we explored the possible contribution of PEA in allergic sensitization, by using ovalbumin (OVA) as sensitizing agent in the mouse. PEA levels were dramatically reduced in the bronchi of OVA-treated animals. This effect was coupled to a significant up-regulation of CB2 and GPR55 receptors, two of the proposed molecular PEA targets, in bronchi harvested from allergen-sensitized mice. PEA supplementation (10 mg/kg, 15 min before each allergen exposure) prevented OVA-induced bronchial hyperreactivity, but it did not affect IgE plasma increase. On the other hand, PEA abrogated allergen-induced cell recruitment as well as pulmonary inflammation. Evaluation of pulmonary sections evidenced a significant inhibitory action of PEA on pulmonary mast cell recruitment and degranulation, an effect coupled to a reduction of leukotriene C4 production. These findings demonstrate that allergen sensitization negatively affects PEA bronchial levels and suggest that its supplementation has the potential to prevent the development of asthma-like features

Surgical treatment of lung cancer with adjacent lobe invasion in relation to fissure integrity

Background Tumor with adjacent lobe invasion (T‐ALI) is an uncommon condition. Controversy still exists regarding the optimal resection of adjacent lobe invasion, and the prognostic value in relation to fissure integrity at the tumor invasion point. The aims of this paper were to evaluate the prognosis of T‐ALI with regard to fissure integrity, and type of resection. Methods This was a retrospective multicenter study which included all consecutive patients with T‐ALI undergoing surgical treatment. Based on radiological, intraoperative and histological findings, T‐ALI patients were differentiated into two groups based on whether the fissure was complete (T‐ALI‐A group) or incomplete (T‐ALI‐D Group) at the level of tumor invasion point. Clinico‐pathological features and survival of two study groups were analyzed and compared. Results Study population included 135 patients, of these 98 (72%) were included into T‐ALI‐A group, and 37 (38%) into T‐ALI‐D Group. T‐ALI‐D patients had better overall survival than T‐ALI‐A patients (63.9 ± 7.0 vs. 48.9 ± 3.9; respectively, P = 0.01) who presented with a higher incidence of lymph node involvement (35% vs. 4%; P = 0.004), and recurrence rate (43% vs. 16%; P = 0.01). At multivariable analysis, T‐ALI‐D (P = 0.01), pN0 stage (P = 0.0002), and pT≤5 cm (P = 0.0001) were favorable survival prognostic factors. Conclusions T‐ALI‐D presented a better prognosis than T‐ALI‐A while extent of resection had no effect on survival. Thus, in patients with small T‐ALI‐D and without lymph node involvement, sublobar resection of adjacent lobe rather than lobectomy could be indicated. Key points The extent of resection of adjacent lobe had no effect on survival while T‐ALI‐D, pN0 stage, and pT≤5 cm were significant prognostic factors. In patients with small T‐ALI‐D and without lymph node involvement, sublobar resection of adjacent lobe could be indicated as an alternative to lobectomy

Palmitoylethanolamide Supplementation during Sensitization Prevents Airway Allergic Symptoms in the Mouse

One important risk factor for the development of asthma is allergen sensitization. Recent increasing evidence suggests a prominent role of mast cells in asthma pathophysiology. Since Palmitoylethanolamide (PEA), an endogenous lipid mediator chemically related to – and co-released with- the endocannabinoid anandamide, behaves as a local autacoid down-regulator of mast cell activation and inflammation, we explored the possible contribution of PEA in allergic sensitization, by using ovalbumin (OVA) as sensitizing agent in the mouse. PEA levels were dramatically reduced in the bronchi of OVA-treated animals. This effect was coupled to a significant up-regulation of CB2 and GPR55 receptors, two of the proposed molecular PEA targets, in bronchi harvested from allergen-sensitized mice. PEA supplementation (10 mg/kg, 15 min before each allergen exposure) prevented OVA-induced bronchial hyperreactivity, but it did not affect IgE plasma increase. On the other hand, PEA abrogated allergen-induced cell recruitment as well as pulmonary inflammation. Evaluation of pulmonary sections evidenced a significant inhibitory action of PEA on pulmonary mast cell recruitment and degranulation, an effect coupled to a reduction of leukotriene C4 production. These findings demonstrate that allergen sensitization negatively affects PEA bronchial levels and suggest that its supplementation has the potential to prevent the development of asthma-like features