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Background: Tracheal stenosis represents a fearsome complication that substantially impairs quality of life. The recent SARS-CoV-2 pandemic increased the number of patients requiring invasive ventilation through prolonged intubation or tracheostomy, increasing the risk of tracheal stenosis. Study design and methods: In this prospective, observational, multicenter study performed in Lombardy (Italy), we have exanimated 281 patients who underwent prolonged intubation (more than 7 days) or tracheostomy for severe COVID-19. Patients underwent CT scan and spirometry 2 months after hospital discharge and a subsequent clinical follow-up after an additional 6 months (overall 8 months of follow-up duration) to detect any tracheal lumen reduction above 1%. The last follow-up evaluation was completed on 31 August 2022. Results: In the study period, 24 patients (8.5%, CI 5.6-12.4) developed tracheal stenosis in a median time of 112 days and within a period of 200 days from intubation. Compared to patients without tracheal stenosis, tracheostomy was performed more frequently in patients that developed stenosis (75% vs 54%, p = 0.034). Tracheostomy and alcohol consumption (1 unit of alcohol per day) increased risk of developing tracheal stenosis of 2.6-fold ( p = 0.047; IC 0.99-6.8) and 5.4-fold ( p = 0.002; CI 1.9-16), respectively. Conclusions : In a large cohort of patients, the incidence of tracheal stenosis increased during pandemic, probably related to the increased use of prolonged intubation. Patients with histories of prolonged intubation should be monitored for at least 200 days from invasive ventilation in order to detect tracheal stenosis at early stage. Alcohol use and tracheostomy are risk factors for developing tracheal stenosis.

Lung transplantation is a key therapeutic option for several end-stage lung diseases. Interventional pulmonology techniques, mostly bronchoscopy, play a key role throughout the whole path of lung transplantation, from donor evaluation to diagnosis and management of post-transplant complications. We carried out a non-systematic, narrative literature review aimed at describing the main indications, contraindications, performance characteristics and safety profile of interventional pulmonology techniques in the context of lung transplantation. We highlighted the role of bronchoscopy during donor evaluation and described the debated role of surveillance bronchoscopy (with bronchoalveolar lavage and transbronchial biopsy) to detect early rejection, infections and airways complications. The conventional (transbronchial forceps biopsy) and the new techniques (i.e. cryobiopsy, biopsy molecular assessment, probe-based confocal laser endomicroscopy) can detect and grade rejection. Several endoscopic techniques (e.g. balloon dilations, stent placement, ablative techniques) are employed in the management of airways complications (ischemia and necrosis, dehiscence, stenosis and malacia). First line pleural interventions (i.e. thoracentesis, chest tube insertion, indwelling pleural catheters) may be useful in the context of early and late pleural complications occurring after lung transplantation. High quality studies are advocated to define endoscopic standard protocols and thus help improving long-term prognostic outcomes of lung transplant recipients., Competing Interests: Declaration of competing interest None of the Authors has conflict of interest to disclose., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Dysregulated systemic inflammation is the primary driver of mortality in severe coronavirus disease 2019 (COVID-19) pneumonia. Current guidelines favour a 7-10-day course of any glucocorticoid equivalent to dexamethasone 6 mg daily. A comparative randomised controlled trial (RCT) with a higher dose and a longer duration of intervention was lacking., Methods: We conducted a multicentre, open-label RCT to investigate methylprednisolone 80 mg as a continuous daily infusion for 8 days followed by slow tapering versus dexamethasone 6 mg once daily for up to 10 days in adult patients with COVID-19 pneumonia requiring oxygen or noninvasive respiratory support. The primary outcome was reduction in 28-day mortality. Secondary outcomes were mechanical ventilation-free days at 28 days, need for intensive care unit (ICU) referral, length of hospitalisation, need for tracheostomy, and changes in C-reactive protein (CRP) levels, arterial oxygen tension/inspiratory oxygen fraction ( P aO 2 / F IO 2 ) ratio and World Health Organization Clinical Progression Scale at days 3, 7 and 14., Results: 677 randomised patients were included. Findings are reported as methylprednisolone (n=337) versus dexamethasone (n=340). By day 28, there were no significant differences in mortality (35 (10.4%) versus 41 (12.1%); p=0.49) nor in median mechanical ventilation-free days (median (interquartile range (IQR)) 23 (14) versus 24 (16) days; p=0.49). ICU referral was necessary in 41 (12.2%) versus 45 (13.2%) (p=0.68) and tracheostomy in 8 (2.4%) versus 9 (2.6%) (p=0.82). Survivors in the methylprednisolone group required a longer median (IQR) hospitalisation (15 (11) versus 14 (11) days; p=0.005) and experienced an improvement in CRP levels, but not in P aO 2 / F IO 2 ratio, at days 7 and 14. There were no differences in disease progression at the prespecified time-points., Conclusion: Prolonged, higher dose methylprednisolone did not reduce mortality at 28 days compared with conventional dexamethasone in COVID-19 pneumonia., Competing Interests: Conflict of interest: F. Salton, P. Confalonieri, S. Centanni, M. Mondoni, N. Petrosillo, D. Lacedonia, A. Voza, N. Carpenè, M. Montico, N. Reccardini, G.U. Meduri, B. Ruaro and M. Confalonieri have no conflicts of interest to disclose. P. Bonfanti received personal fees from ViiV Healthcare, Gilead, Janssen, Merck and Pfizer, not related to this work. G. Lapadula received personal fees from ViiV Healthcare and Pfizer, not related to this work., (Copyright ©The authors 2023.)

Radiation therapy has become the standard of care in the treatment of canine intranasal neoplasia, but because of the poor prognosis associated with stage IV nasal tumours and the proximity of the brain to the irradiation target, few data regarding the treatment of very advanced neoplasms are available. The aim of this pilot study was to evaluate the feasibility, safety and effectiveness of a combined treatment composed of definitive high-dose hypofractionated volumetric modulated arc radiotherapy on tumours with concurrent treatment of regional lymph nodes if positive or as prophylaxis, carboplatin radio-sensitising, and adjuvant metronomic chemotherapy for stage IV canine nasal tumours with intracranial extension. A pilot observational study was conducted in 7 dogs. Magnetic resonance imaging follow-up examinations revealed complete responses in 5 dogs and partial responses in 2. The median overall survival time, evaluated via Kaplan-Meier survival analysis, was 310 days with a 95% confidence interval of 210-400 days, whereas the median progression-free survival was 240 days with a 95% confidence interval of 190-290 days. Despite the proximity of highly sensitive organs at risk, no grade III or IV toxicities were observed, and volumetric modulated arc radiotherapy seemed to be a feasible treatment option for stage IV canine nasal tumours where conformal 3D radiotherapy has proven to give higher doses with severe damage to the surrounding unaffected tissues. Further studies are needed on the role of the sphenoid bone microscopic infiltration and regional lymph node involvement. The absence of severe toxicity could also lead to a dose escalation study and chemotherapy scheme., (Copyright © 2022. Published by Elsevier Inc.)

Gliomas are the second-most-common primary brain tumors in dogs. Surgery and radiotherapy are established treatment approaches with similar median survival time, whereas conventional chemotherapy is burdened by severe adverse effects. Spinal and leptomeningeal spread of gliomas have been described following radiotherapy treatment alone. The purpose of this study was to evaluate the outcome for four dogs with primary high-grade gliomas in the forebrain without evidence, at diagnosis, of neoplastic invasion along the spinal cord, that were treated with concomitant chemotherapy (temozolomide) and hypofractionated volumetric-modulated arc radiotherapy (VMAT-RT). Temozolomide was selected for its radiosensitive properties, and radiotherapy dose protocols of 37 Gy in 7 fractions or 42 Gy in 10 fractions were used. After an initial complete or partial response, tumors recurred across the cranial-spinal pathway. Post-mortem macroscopic examinations confirmed swollen spinal cord and hyperemic meningeal sleeve, with nodular lesions on the meningeal surface. Microscopically, infiltration of the spinal cord and meninges by neoplastic cells (with features of oligodendrogliomas) were observed. This work seems to suggest that the entire central nervous system should be investigated in diagnostic examinations of canine gliomas. Dose-escalation trials and/or spinal cord prophylaxis treatment could also be evaluated to prevent tumor progression.

The aims of this pilot study were to evaluate the feasibility and efficacy of high-dose hypofractionated volumetric modulated arc radiotherapy (VMAT) applied to whole pelvic region radiotherapy (WPRT) with multilevel simultaneous integrated boost (MLSIB) combined with piroxicam and chemotherapy for the treatment of canine transitional cell carcinoma (TCC) of the lower urinary tract with muscle invasion TCC. Twelve dogs were enrolled, according to stage, in two groups: group 1, TCC confined to the urinary tract; group 2, TCC with metastasis. The planning target volume dose was tailored from 36 to 42 Gy in 6 fractions. All dogs were prescribed piroxicam and radiosensitizing carboplatin, and six received chemotherapy after radiotherapy. Serial follow-ups with computed tomography and magnetic resonance imaging were performed. Disease control and toxicity effects were evaluated according to the Response Evaluation Criteria in Solid Tumors and Veterinary Radiation Therapy Oncology Group criteria. The treatment was well tolerated, and no high-grade side effects were reported. The median overall survival times for groups 1 and 2 were 1,230 and 150 days, respectively. A considerable percentage of patients in group1 (50%) were still alive at the time of writing this paper, and a longer follow-up could enable a more accurate survival analysis. This preliminary analysis shows that VMAT applied to the WPRT with MLSIB is an effective and safe option for dogs with lower urinary TCC, although the presence of metastases worsens the prognosis.

The aim of this prospective pilot study was to evaluate the feasibility and effectiveness of curative intent high dose hypofractionated frameless volumetric modulated arc radiotherapy for treatment of canine trigeminal peripheral nerve sheath tumors. Client-owned dogs with a presumptive imaging-based diagnosis of trigeminal peripheral nerve sheath tumor were recruited for the study during the period of February 2010 to December 2013. Seven dogs were enrolled and treated with high dose hypofractionated volumetric modulated arc radiotherapy delivered by a 6 MV linear accelerator equipped with a micro-multileaf beam collimator. The plans were computed using a Monte Carlo algorithm with a prescription dose of 37 Gy delivered in five fractions on alternate days. Overall survival was estimated using a Kaplan-Meier curve analysis. Magnetic resonance imaging (MRI) follow-up examinations revealed complete response in one dog, partial response in four dogs, and stable disease in two dogs. Median overall survival was 952 days with a 95% confidence interval of 543-1361 days. Volumetric modulated arc radiotherapy was demonstrated to be feasible and effective for trigeminal peripheral nerve sheath tumor treatment in this sample of dogs. The technique required few sedations and spared organs at risk. Even though larger studies are required, these preliminary results supported the use of high dose hypofractionated volumetric modulated arc radiotherapy as an alternative to other treatment modalities., (© 2018 American College of Veterinary Radiology.)

A prospective study to assess high-dose hypofractionated volume modulated arc radiotherapy feasibility and efficacy in canine meningiomas was conducted. Thirty-nine patients with encephalic and spinal meningiomas assumed from MRI findings were recruited and received high-dose hypofractionated volumetric modulated arc radiotherapy by a linear accelerator equipped with an external beam modulator micro-multileaf collimator and an XVI cone beam computed tomography system. The prescribed mean dose was 33 Gy in five fractions. The treatment feasibility was tested through planned and delivered dose agreement checks. Regular clinical examinations were performed during and after irradiation time, with regard to mentation, deambulation, cranial nerve dysfunction, and seizures. Serial MRI exams were done 60 days after irradiation and after 4, 6, 12, 18, and 24 mo. Volumetric disease reduction criteria implemented with clinical neurological systematic evaluation were adopted to assess the course and to categorize patients' responses. Complete and partial responses were observed on the whole in 65.5% of alive patients 24 mo after irradiation. Two-yr overall and disease-specific survival rates were 74.3% and 97.4%, respectively, and the putative radiotoxic effects were found to be few and slight.

Background: We estimated the association between combined hormonal contraceptive (CHC) use and breast cancer (BC) incidence in a well-selected population of women at familial risk of BC at the Modena Family Cancer Clinic., Materials and Methods: We performed a retrospective cohort study by reviewing the data from 2527 women (4.5% BRCA mutation carriers, 72.2% high risk, and 23.3% intermediate risk using the Modena criteria and the Tyrer-Cuzick model)., Results: We did not find any specific feature of breast cancer (infiltration, hormone receptor and HER2 status, onset before age 35 years, multiple diagnoses) in the CHC users (P > .05). Only 2.0% of women used a preparation with ≥ 50 μg of ethinylestradiol (EE). The use of CHCs was not associated with an increased risk of breast cancer (cumulative hazard: never used, 0.17; CHC users, 0.20; P = .998), regardless of the duration of use (cumulative hazard: never used, 0.17, used < 5 years, 0.20; used 5-10 years, 0.14; used > 10 years, 0.25; P = .414). This was confirmed for the different risk groups when interacted in a Cox proportional hazard regression model. The EE dose did not influence the risk of BC (cumulative hazard, 2.37; 95% confidence interval, 0.53-10.1; never used, 0.18; EE < 20 μg used, 0.04; EE ≥ 20 μg used, 0.16; P = .259). The types of progestins used might influence the risk, with some, such as gestodene (P = .028) and cyproterone acetate (P = .031), associated with an even greater reduced risk., Conclusions: CHC use does not increase the risk of BC in a population of women with a family history, encouraging CHC use in this group of women., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Volumetric Modulated Arc Therapy (VMAT) is a modern technique, widely used in human radiotherapy, which allows a high dose to be delivered to tumor volumes and low doses to the surrounding organs at risk (OAR). Veterinary clinics takes advantage of this feature due to the small target volumes and distances between the target and the OAR. Sparing the OAR permits dose escalation, and hypofractionation regimens reduce the number of treatment sessions with a simpler manageability in the veterinary field. Multimodal volumes definition is mandatory for the small volumes involved and a positioning device precisely reproducible with a setup confirmation is needed before each session for avoiding missing the target. Additionally, the elaborate treatment plan must pursue hard constraints and objectives, and its feasibility must be evaluated with a per patient quality control. The aim of this work is to report results with regard to brain meningiomas and gliomas, trigeminal nerve tumors, brachial plexus tumors, adrenal tumors with vascular invasion and rabbit thymomas, in comparison with literature to determine if VMAT is a safe and viable alternative to surgery or chemotherapy alone, or as an adjuvant therapy in pets., Competing Interests: The authors declare no conflict of interest

Atlanto-axial (AA) instability due to ligament insufficiency is a common cause of cervical spinal cord compression in toy breeds. However, in some dogs a difference in size between the atlas and the axis leads to joint incongruence that exacerbates AA subluxation and makes surgical treatment challenging. Twelve dogs with AA instability with incongruence were enrolled in a single institution prospective observational study. Computed tomography (CT) and magnetic resonance imaging (MRI) of the AA joint were compared to a retrospectively reviewed control group. A novel surgical approach consisting of a dorsal internal fixation technique was performed in six dogs. For affected dogs, the mean normalised difference between the dorso-ventral atlas canal and the dorso-ventral axis canal was 29.67% (median of 35.07%, standard deviation 25.64%), while in normal dogs a mean difference of 4.67% (median of 3.95%, standard deviation 5.21%) was observed. On MRI, 12/12 affected dogs had spinal cord compression, which was classified as reducible (3/12), partially reducible (6/12) and non-reducible (3/12). In surgically operated dogs, follow-up CT showed a partial or complete reduction of the previous spinal cord compression with a consistent amelioration or resolution of the presenting complaints. The proposed surgical technique was safe and effective in dogs with partially or completely reducible spinal cord compression.

Reproductive history and exogenous hormonal exposures are acknowledged risk factors for breast cancer in the general population. In women at increased breast cancer risk for genetic predisposition or positive family history, data regarding these risk factors are limited or conflicting, and recommendations for these categories are unclear. We evaluated the characteristics of reproductive life in 2522 women at increased genetic or familial breast cancer risk attending our Family Cancer Center. Breast cancers in BRCA mutation carriers were more likely to be hormone receptor negative, diagnosed at 35 years or before and multiple during the lifetime than tumors in women at increased familial risk, while the distribution of invasive cancers and HER2 positive tumors was similar in the different risk groups. At least one full-term pregnancy (HR 0.27; 95% CI 0.12-0.58; p = 0.001), breastfeeding either less (HR 0.24; 95% CI 0.09-0.66; p = 0.005) or more (HR 0.25; 95% IC 0.08-0.82; p = 0.022) than one year and late age at menopause (HR 0.10; 95% CI 0.01-0.82; p = 0.033) showed to be protective factors in BRCA mutation carriers, while in women at increased familial risk early age at first full-term pregnancy (HR 0.62; 95% IC 0.38-0.99; p = 0.048) and late menarche (HR 0.61; 95% CI 0.42-0.85; p = 0.004) showed to be the main protective factors. Finally, for the entire population, combined hormonal contraceptives demonstrated to do not increase breast cancer risk. The results of our study suggest that women at high familial risk and mutation carries develop tumors with different clinical-pathological characteristics and, consequently, are influenced by different protective and risk factors.

Objective: Treatment of canine peripheral nerve sheath tumours (PNSTs) is challenging and prognosis after surgical resection is considered poor. The aim of this study was to evaluate the feasibility and effectiveness of stereotactic radiotherapy (RT) of these tumours., Methods: 10 dogs with clinical symptoms and MRI findings consistent with PNSTs of the brachial plexus, branches and nerve roots were treated with linear accelerator-based volumetric-modulated arc radiotherapy (VMAT) with a dose of 35 Gy/5 fractions. Clinical and MRI follow-up examinations were planned and radiotoxicity and survival times were investigated., Results: Tumours involved the plexus and proximal nerves in three dogs, the plexus, proximal nerves and nerve roots in five dogs and the nerve roots and proximal nerves in two dogs. Partial response and partial or complete reductions of neurological deficits were observed in all the treated dogs. Local recurrence was observed in 9/10 of treated dogs. No symptom directly referable to radiotoxicity was observed. Mean overall survival of 371 ± 30 days [95% confidence interval (CI) of (315-427)] and mean progression-free survival of 240 ± 30 days (95% CI of 188-291) from this work are comparable with surgical literature data regarding the plexus and proximal nerve localization, but are superior in comparison with nerve root localization., Conclusion: VMAT can be a safe and viable alternative to surgery in cases of canine brachial plexus PNSTs involving the proximal nerves and nerve roots. Advances in knowledge: To our knowledge, this is the first prospective observational clinical study regarding VMAT stereotactic RT treatment for canine brachial plexus PNSTs and suggests that VMAT may achieve at least similar clinical outcome than surgery in a safer way.

The aim of this work was to present a novel minimally invasive surgical stabilization technique for canine atlanto-occipital dislocation and to report the associated magnetic resonance imaging (MRI) findings. All 5 dogs in this case series underwent 1.5 T MRI of the head and neck and 3 underwent both MRI and computed tomography (CT). Atlanto-occipital dislocations were diagnosed based on the increased joint space between the occipital condyles and the atlas on MRI. Surgery was performed immediately with a never previously described fixation technique based on an external ligature. The stabilization was performed via 4 holes drilled in the zygomatic processes and in the atlas wings on each side. A nylon monofilament of 1 mm diameter was inserted in the 4 holes, and an O-shaped ligature was carried out externally to the skin through the ipsilateral zygomatic arch. Ligatures were removed within 2 months. At the postsurgical follow-up examination, 14 days after surgery, all dogs were found to be ambulatory. Atlanto-occipital stability was assessed by clinical examination with an average of 24 months of follow-up. The positive outcomes in this case series suggest that atlanto-occipital dislocation may be surgically treated with this novel technique, irrespective of the severity of the clinical presentation and associated lesions observed on MRI.

Thymoma is a relatively common tumor in rabbits. Treatment with surgery, radiation therapy, and chemotherapy alone or in combination has been reported with varying outcomes. Stereotactic volumetric modulated arc radiotherapy delivered in a hypofractionated manner allows high doses of radiation to be delivered to the target volume while allowing sparing of adjacent critical structures. This therapy is ideally suited for thymomas in rabbits given their size, the difficulty of multiple anesthesia episodes and the complexity of the radiotherapy plans required due to the tumor's proximity to the heart, lungs, and mediastinal structures. Fifteen rabbits with thymoma were prospectively recruited for this observational, single institution, single arm clinical study. All rabbits were imaged with both computed tomography (CT) and magnetic resonance imaging (MRI). A total dose of 40 Gy in six fractions was delivered using a single arc over an 11-day period with repeat CT simulation done every other fraction for adaptive planning. Follow-up evaluation was done through repeat CT and MRI imaging and revealed complete responses using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Two rabbits had died at 618 and 718 days, 10 were alive and three were lost to follow-up. Observed acute and late effects were graded according to the Veterinary Radiation Therapy Oncology Group (VRTOG) criteria and were found to be minimal., (© 2016 American College of Veterinary Radiology.)