Endoscopic sinus surgery in individuals with facial pain due to chronic maxillary sinusitis ? a functional controlled study

Objective: To measure the intra-sinus pressure and the maxillary sinus functional efficiency (MSFE) in individuals with chronic facial pain after conservative or conventional endoscopic maxillary surgery, as well as in controls. Method: Sinus manometry was performed 5 times during inhalation. Results: The resemblance of pressure values comparing those treated with minimally invasive surgery and controls was remarkable, while traditional surgery significantly decreased intrasinusal pressures. The MSFE was 100% in the three tested times for controls, close to that in those submitted to minimally invasive surgery (98.3%, 98.8%, and 98.0%) and significantly impaired after conventional surgery (48.8%, 52.1%, 48.5 %, p<0.01). All patients submitted to minimally invasive surgery remained pain-free after three months of surgery, relative to 46.7% of the submitted to conventional surgery (p<0.05). Conclusion: Minimally invasive sinus surgery is associated with functionality of the chambers that resemble what is found in normal individuals

Disease Rescue and Increased Lifespan in a Model of Cardiomyopathy and Muscular Dystrophy by Combined AAV Treatments

The BIO14.6 hamster is an excellent animal model for inherited cardiomyopathy, because of its lethal and well-documented course, due to a spontaneous deletion of delta-sarcoglycan gene promoter and first exon. The muscle disease is progressive and average lifespan is 11 months, because heart slowly dilates towards heart failure.Based on the ability of adeno-associated viral (AAV) vectors to transduce heart together with skeletal muscle following systemic administration, we delivered human delta-sarcoglycan cDNA into male BIO14.6 hamsters by testing different ages of injection, routes of administration and AAV serotypes. Body-wide restoration of delta-SG expression was associated with functional reconstitution of the sarcoglycan complex and with significant lowering of centralized nuclei and fibrosis in skeletal muscle. Motor ability and cardiac functions were completely rescued. However, BIO14.6 hamsters having less than 70% of fibers recovering sarcoglycan developed cardiomyopathy, even if the total rescued protein was normal. When we used serotype 2/8 in combination with serotype 2/1, lifespan was extended up to 22 months with sustained heart function improvement.Our data support multiple systemic administrations of AAV as a general therapeutic strategy for clinical trials in cardiomyopathies and muscle disorders

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P &lt; .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Taller de concordancia en la evaluación de imágenes capilaroscópicas

Introducción: la capilaroscopia es un método no invasivo que permite observar la microvasculatura en el área periungueal. Los resultados informados pueden ser altamente variables entre distintos observadores. A lo largo del tiempo surgieron métodos cuantitativos y semicuantitativos para mejorar la reproducibilidad. Objetivos: conocer el nivel de acuerdo intra e interobservador al informar los diferentes patrones capilaroscópicos en individuos con diferente nivel de entrenamiento. Materiales y métodos: estudio de corte transversal. Participaron médicos reumatólogos especialistas y en formación que habían realizado previamente un curso virtual de capacitación en capilaroscopia. Recibieron 40 imágenes capilaroscópicas proyectadas en una presentación de PowerPoint y debían responder a través de un cuestionario digital. Se evaluó la concordancia de respuestas intra e interobservador. Resultados: se encontró un alto nivel de concordancia global con un kappa 0,66 IC 95% (0,63-0,70) p<0,0000. También en otros grupos como reumatólogos en formación: kappa 0,65 IC 95% (0,60-0,71) p=0,0000, y médicos reumatólogos: kappa 0,67 IC 95% (0,62-0,72) p=0,0000. Conclusiones: el nivel de concordancia encontrado fue globalmente alto, independientemente del nivel de entrenamiento de los profesionales, y de ser o no reumatólogo. La concordancia fue superior cuando se comparó a quienes tenían más de 4 años de experiencia en la realización de videocapilaroscopia

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Magnetic resonance imaging in the pre-operative evaluation of obstructive epiphora: true-FISP and VIBE vs gadolinium

Purpose: To assess unenhanced magnetic resonance imaging (MRI) in the preoperative evaluation of obstructive epiphora in patients undergoing dacryocystorhinostomy (DCR) and in particular, to evaluate the efficacy of this technique in the detection of the exact level of obstruction occurring in the naso-lachrymal duct (NLD). The correct identification and characterization of the NLD and its obstructions lead to a more effective surgery, preventing recurrent dacryocystitis after the surgical treatment. Methods: From January 2009 to December 2014, 127 obstructive epiphoras were diagnosed and treated in 127 patients (35 M, 92 F; mean age 60.7 ± 7.48 years, range 42–75 years) with endoscopic DCR, in a IRB-approved protocol. To precisely define the morphology of the NLD and the site of obstruction, some of these patients (67/127) underwent unenhanced 1.5-T MR with TrueFISP and VIBE sequences, while the remaining (60/127) underwent Gadolinium-enhanced 1.5-T MR. Afterwards, surgery checked the real site of obstruction in both groups of patients (enhanced and unenhanced MR), with surgical outcomes matched with previous MR reports. Results: In all cases, unenhanced MRI was able to detect the exact site of obstruction along the NLD, allowing a correct planning of surgical endoscopic procedures. On the contrary, enhanced MRI wrongly diagnosed six patients with proximal stenosis (6/60, 10.0%) as intermediate NLD obstruction. Unenhanced MRI was found to be more accurate than enhanced MRI with a statistical significant difference (p value = 0.0256) and obviously cheaper and easier to perform. All imaging reports were verified with surgery. The correct identification of the level of obstruction allowed successful surgery in around 73% (93/127) of patients, who had no recurrence during 6-month follow-up. Conclusion: In patients with epiphora, unenhanced MR showed to be highly reliable and even more effective than enhanced MR in the preoperative characterization of NLD stenosis, with no need of performing complex, time-wasting and expensive procedures for the administration of topical contrast media

Identification of a novel subpopulation of Caspase-4 positive non-small cell lung Cancer patients.

Background: Therapy/prognosis of Non-Small Cell Lung Cancer (NSCLC) patients are strongly related to gene alteration/s or protein expression. However, more than 50% of NSCLC patients are negative to key drugable biomarkers. Methods: We used human samples of NSCLC and mouse models of lung adenocarcinoma. Results: We showed that caspase-4 was highly present in the tumor mass compared to non-cancerous human tissues. Interestingly, the orthologue murine caspase-11 promoted lung carcinogenesis in mice. Carcinogen-exposed caspase-11 knockout mice had lower tumor lesions than wild type mice, due to the relevance of caspase-11 in the structural lung cell as demonstrated by bone marrow transplantation and adoptive transfer experiments. Similarly to what observed in mice, caspase-4 was correlated to the stage of lung cancer in humans in that it induced cell proliferation in a K-Ras, c-MyC and IL-1α dependent manner. Caspase-4 positive adenocarcinoma (79.3%) and squamous carcinoma (88.2%) patients had lower median survival than patients who had lower levels of caspase-4. Moreover, PD-L1 expression and gene mutation (i.e. EGFR) were not correlated to caspase-4 expression. Instead, NSCLC patients who had K-Ras or c-MyC gene alteration were positively correlated to higher levels of caspase-4 and lower survival rate. Conclusions: We identified a subgroup of NSCLC patients as caspase-4 positive among which double and triple positive caspase-4, K-Ras and/or c-MyC patients which prognosis was poor. Because K-Ras and c-MyC are still undrugable, the identification of caspase-4 as a novel oncoprotein could introduce novelty in the clinical yet unmet needs for NSCLC patients