SNP of Aromatase Predict Long-term Survival and Aromatase Inhibitor Toxicity in Patients with Early Breast Cancer: A Biomarker Analysis of the GIM4 and GIM5 Trials.

PURPOSE: In estrogen receptor-positive (ER+) breast cancer, single-nucleotide polymorphisms (SNP) in the aromatase gene might affect aromatase inhibitors (AI) metabolism and efficacy. Here, we assessed the impact of SNP on prognosis and toxicity of patients receiving adjuvant letrozole. EXPERIMENTAL DESIGN: We enrolled 886 postmenopausal patients in the study. They were treated with letrozole for 2 to 5 years after taking tamoxifen for 2 to 6 years, continuing until they completed 5 to 10 years of therapy. Germline DNA was genotyped for SNP rs4646, rs10046, rs749292, and rs727479. Log-rank test and Cox model were used for disease-free survival (DFS) and overall survival (OS). Cumulative incidence (CI) of breast cancer metastasis was assessed through competing risk analysis, with contralateral breast cancer, second malignancies and non-breast cancer death as competing events. CI of skeletal and cardiovascular events were assessed using DFS events as competing events. Subdistribution HR (sHR) with 95% confidence intervals were calculated through Fine-Gray method. RESULTS: No SNP was associated with DFS. Variants rs10046 [sHR 2.03, (1.04-2.94)], rs749292 [sHR 2.11, (1.12-3.94)], and rs727479 [sHR 2.62, (1.17-5.83)] were associated with breast cancer metastasis. Three groups were identified on the basis of the number of these variants (0, 1, >1). Variant-based groups were associated with breast cancer metastasis (10-year CI 2.5%, 7.6%, 10.7%, P = 0.035) and OS (10-year estimates 96.5%, 93.0%, 89.6%, P = 0.030). Co-occurrence of rs10046 and rs749292 was negatively associated with 10-year CI of skeletal events (3.2% vs. 10%, P = 0.033). A similar association emerged between rs727479 and cardiovascular events (0.3% vs. 2.1%, P = 0.026). CONCLUSIONS: SNP of aromatase gene predict risk of metastasis and AI-related toxicity in ER+ early breast cancer, opening an opportunity for better treatment individualization.

cDCD organ donation pathway of Romagna Local Health Authority: strategic planning, organizational management, and results.

The introduction of pathways to enrol deceased donors after cardio-circulatory confirmation of death (donation after circulatory death, DCD) is expanding in many countries to face the shortage of organs for transplantation. The implementation of normothermic regional reperfusion (NRP) with warm oxygenated blood is a strategy to manage in-situ the organs of DCD donors. This approach, an alternative to in-situ cold preservation, and followed by prompt retrieval and cold static storage and/or ex-vivo machine perfusion (EVMP), could be limited to abdominal organs (A-NRP) or extended to the thorax (thoraco-abdominal, TA-NRP. NRP is also referred to as extracorporeal interval support for organ retrieval (EISOR). The use of EISOR is increasing in Europe, even if variably regulated. A-NRP has been demonstrated to be effective in decreasing the risk associated with transplantation of abdominal organs from DCD donors, and was recommended by the European Society for Organ Transplantation (ESOT) in a recent consensus document. We aim to explain how we select the candidates for DCD, to describe our regionalized model for implementing EISOR provision, and to introduce the health care professionals involved in this complex process, with their strictly defined roles, responsibilities, and boundaries. Finally, we report the results of our program, recruiting cDCD donors over a large network of hospitals, all pertaining to a Local Health Authority (Azienda Unità Sanitaria Locale, AUSL) in Romagna, Italy.

Massive aspiration syndrome: a possible indication for "emergent" veno-venous extracorporeal membrane oxygenation?: a case report.

BACKGROUND: Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is usually performed in cases of severe respiratory failure in which conventional and advanced mechanical ventilation strategies are ineffective in achieving true lung-protective ventilation, thus triggering ventilatory-induced lung injury. If circulatory failure coexists, veno-arterial ECMO (VA-ECMO) may be preferred over VV-ECMO because of its potential for circulatory support. In VA-ECMO, the respiratory contribution is less effective and the complication rate is higher than in the VV configuration. CASE PRESENTATION: The authors present a case in which VV-ECMO was performed in an emergency setting to treat a 68-year-old White male patient who experienced acute respiratory failure after massive aspiration. Despite intubation and intensive care unit admission, multiple organ failure occurred suddenly, thus prompting referral to a level-1 trauma center with an ECMO facility. The patient's condition slowly improved with VV-ECMO support along with standard treatment for hemodynamic impairment. VV-ECMO was discontinued on day 8. The patient was extubated on day 14 and discharged home fully recovered 34 days after the event. CONCLUSIONS: Attention was focused on the decision to initiate VV-ECMO support even in the presence of severe hemodynamic derangement, although VA-ECMO could have provided better hemodynamic support but less effective respiratory support.

Clinical Course and Risk Factors for In-Hospital Mortality of 205 Patients with SARS-CoV-2 Pneumonia in Como, Lombardy Region, Italy.

The aim of this study is to explore risk factors for in-hospital mortality and describe the effectiveness of different treatment strategies of 205 laboratory-confirmed cases infected with SARS-CoV-2 during the Lombardy outbreak. All patients received the best supportive care and specific interventions that included the main drugs being tested for repurposing to treat COVID-19, such as hydroxychloroquine, anticoagulation and antiviral drugs, steroids, and interleukin-6 pathway inhibitors. Clinical, laboratory, and treatment characteristics were analyzed with univariate and multivariate logistic regression methods to explore their impact on in-hospital mortality. Univariate analyses showed prognostic significance for age greater than 70 years, the presence of two or more relevant comorbidities, a P/F ratio less than 200 at presentation, elevated LDH (lactate dehydrogenase) and CRP (C-reactive protein) values, intermediate- or therapeutic-dose anticoagulation, hydroxychloroquine, early antiviral therapy with lopinavir/ritonavir, short courses of steroids, and tocilizumab therapy. Multivariable regression confirmed increasing odds of in-hospital death associated with age older than 70 years (OR 3.26) and a reduction in mortality for patients treated with anticoagulant (-0.37), antiviral lopinavir/ritonavir (-1.22), or steroid (-0.59) therapy. In contrast, hydroxychloroquine and tocilizumab have not been confirmed to have a significant effect in the treatment of SARS-CoV-2 pneumonia. Results from this real-life single-center experience are in agreement and confirm actual literature data on SARS-CoV-2 pneumonia in terms of both clinical risk factors for in-hospital mortality and the effectiveness of the different therapies proposed for the management of COVID19 disease.

PONDx: real-life utilization and decision impact of the 21-gene assay on clinical practice in Italy.

Clinicopathological prognostic features have limited value to identify with precision newly diagnosed patients with hormone receptor (HR)-positive, HER2-negative breast cancer (BC), who would benefit from chemotherapy (CT) in addition to adjuvant hormonal therapy (HT). The 21-gene Oncotype DX Breast Recurrence Score® (RS) assay has been demonstrated to predict CT benefit, hence supporting personalized decisions on adjuvant CT. The multicenter, prospective, observational study PONDx investigated the real-life use of RS® results in Italy and its impact on treatment decisions. Physicians' treatment recommendations (HT ± CT) were documented before and after availability of RS results, and changes in recommendations were determined. In the HR+ HER2- early BC population studied (N = 1738), physicians recommended CT + HT in 49% of patients pre-RS. RS-guided treatment decisions resulted in 36% reduction of CT recommendations. PONDx confirms that RS results provide clinically relevant information for CT recommendation in early-stage BC, resulting in a reduction of more than a third of CT use.

Trauma and donation after circulatory death: a case series from a major trauma center.

Even with encouraging recipient outcomes, transplantation using donation after circulatory death (DCD) is still limited. A major barrier to this type of transplantation is the consequences of warm ischemia on graft survival; however, preservation techniques may reduce the consequences of cardiac arrest and provide better organ conservation. Furthermore, DCD in trauma patients could further expand organ donation. We present five cases in which organs were retrieved and transplanted successfully using normothermic regional perfusion (NRP) in trauma patients. Prompt critical care support and surgical treatment allowed us to overcome the acute phase. Unfortunately, owing to the severity of their injuries, all of the donors died. However, the advanced and continuous organ-specific supportive treatment allowed the maintenance of general clinical stability and organ preservation. Consequently, it was possible to retrieve and transplant the donors' organs. Death was ascertained in accordance with cardio-circulatory criteria, which was followed by NRP. We consider that DCD in trauma patients may represent an important source of organs.

Lung mechanics in type L CoVID-19 pneumonia: a pseudo-normal ARDS.

BACKGROUND: This study was conceived to provide systematic data about lung mechanics during early phases of CoVID-19 pneumonia, as long as to explore its variations during prone positioning. METHODS: We enrolled four patients hospitalized in the Intensive Care Unit of "M. Bufalini" hospital, Cesena (Italy); after the positioning of an esophageal balloon, we measured mechanical power, respiratory system and transpulmonary parameters and arterial blood gases every 6 hours, just before decubitus change and 1 hour after prono-supination. RESULTS: Both respiratory system and transpulmonary compliance and driving pressure confirmed the pseudo-normal respiratory mechanics of early CoVID-19 pneumonia (respectively, CRS 40.8 ml/cmH2O and DPRS 9.7 cmH2O; CL 53.1 ml/cmH2O and DPL 7.9 cmH2O). Interestingly, prone positioning involved a worsening in respiratory mechanical properties throughout time (CRS,SUP 56.3 ml/cmH2O and CRS,PR 41.5 ml/cmH2O - P 0.37; CL,SUP 80.8 ml/cmH2O and CL,PR 53.2 ml/cmH2O - P 0.23). CONCLUSIONS: Despite the severe ARDS pattern, respiratory system and lung mechanical properties during CoVID-19 pneumonia are pseudo-normal and tend to worsen during pronation. TRIAL REGISTRATION: Restrospectively registered.

Clinical, electromyographical, histopathological characteristics of COVID-19 related rhabdomyolysis.

Rhabdomyolysis is an uncommon complication of the coronavirus disease 2019 (COVID-19) infection. Previous reports have described its management and treatment in medical units, but have not discussed confirmatory tests or differential diagnosis. We report a case of a 58 year-old male patient, who was admitted for COVID-19 pneumonia and subsequently developed severe weakness, inability to move limbs, acute renal failure, significantly elevated myoglobin and creatinine kinase, and was diagnosed with rhabdomyolysis. Continuous renal replacement therapy, the treatment modality of choice over hyperhydration due to ongoing mechanical ventilation, was effective in resolving symptoms. No direct viral invasion of muscles was noted on biopsy. Here, we describe his symptoms, electromyography, and muscular biopsy results, and further discuss the possible differential diagnoses. Neuromuscular symptoms related to COVID-19 require careful clinical analysis. In addition, detailed reports of patients' course of illness and diagnoses will assist in improving care for affected patients.

Less is more: lung-sparing direct repair of a traumatic rupture of the bronchus intermedius.

Major trauma is one of the most common causes of death in the western world in the young population (15-25 years). Thoracic trauma represents 25% of traumatic deaths, and the incidence of tracheobronchial injuries in literature is lower than 5%. Nevertheless, airway injuries are life-threatening conditions. Here we present a case of a 25-year-old patient who underwent a severe motorcycle crash. The injury severity score (ISS) was 35 at admission to the hospital. A right middle bronchus laceration <2 cm involving the whole thickness of the wall of the bronchus intermedius was identified. An urgent right posterolateral thoracotomy was performed, and the lesion was directly repaired. A conservative intervention was the key to grant our patient a healthy life.

Eribulin in Male Patients With Breast Cancer: The First Report of Clinical Outcomes.

BACKGROUND: Evidence on the management and treatment of male breast cancer is scant. We report the analysis of a multicenter Italian series of patients with male breast cancer treated with eribulin. To our knowledge, this is the first report on the use or eribulin in this setting. PATIENTS AND METHODS: Patients were retrospectively identified in 19 reference centers. All patients received eribulin treatment, according to the standard practice of each center. Data on the identified patients were collected using a standardized form and were then centrally reviewed by two experienced oncologists. RESULTS: A total of 23 patients (median age, 64 years; range, 42-80) were considered. The median age at the time of diagnosis of breast cancer was 57 years (range, 42-74). HER2 status was negative in 14 patients (61%), and 2 patients (9%) had triple-negative disease. The most common metastatic sites were the lung (n = 14; 61%) and bone (n = 13; 56%). Eribulin was administered for a median of 6 cycles (range, 3-15). All patients reported at least stable disease; two complete responses (9%) were documented. Eribulin was well-tolerated, with only four patients (17%) reporting grade 3 adverse events and two (9%) with treatment interruptions because of toxicity. Eight subjects (35%) did not report any adverse event during treatment. For patients with a reported fatal event, the median overall survival from the diagnosis of metastatic disease was 65 months (range, 22-228). CONCLUSION: Although hampered by all the limitations of any retrospective case series, the results of the present study suggest, for the first time, the use of eribulin as therapy for male breast cancer. IMPLICATIONS FOR PRACTICE: Evidence on the management and treatment of male breast cancer is eagerly awaited. Although hampered by all the limitations of any retrospective case series, the results of the present study suggest, for the first time, the use of eribulin as therapy for male breast cancer.

LED vs halogen light-curing of adhesive-precoated brackets.

OBJECTIVE: To test the hypothesis that bonding with a blue light-emitting diode (LED) curing unit produces no more failures in adhesive-precoated (APC) orthodontic brackets than bonding carried out by a conventional halogen lamp. MATERIALS AND METHODS: Sixty-five patients were selected for this randomized clinical trial, in which a total of 1152 stainless steel APC brackets were employed. In order to carry out a valid comparison of the bracket failure rate following use of each type of curing unit, each patient's mouth was divided into four quadrants. In 34 of the randomly selected patients, designated group A, the APC brackets of the right maxillary and left mandibular quadrants were bonded using a halogen light, while the remaining quadrants were treated with an LED curing unit. In the other 31 patients, designated group B, halogen light was used to cure the left maxillary and right mandibular quadrants, whereas the APC brackets in the remaining quadrants were bonded using an LED dental curing light. The bonding date, the type of light used for curing, and the date of any bracket failures over a mean period of 8.9 months were recorded for each bracket and, subsequently, the chi-square test, the Yates-corrected chi-square test, the Fisher exact test, Kaplan-Meier survival estimates, and the log-rank test were employed in statistical analyses of the results. RESULTS: No statistically significant difference in bond failure rate was found between APC brackets bonded with the halogen light-curing unit and those cured with LED light. However, significantly fewer bonding failures were noted in the maxillary arch (1.67%) than in the mandibular arch (4.35%) after each light-curing technique. CONCLUSIONS: The hypothesis cannot be rejected since use of an LED curing unit produces similar APC bracket failure rates to use of conventional halogen light, with the advantage of a far shorter curing time (10 seconds).

Epirubicin-vinorelbine intravenous combination followed by oral vinorelbine as first-line treatment in metastatic breast cancer.

Epirubicin and vinorelbine are considered active drugs in metastatic breast cancer. The optimal duration of a chemotherapy regimen for metastatic breast cancer patients is still unknown. Nevertheless, epirubicin has a dose-limiting cardiotoxicity. Vinorelbine is also available as oral formulation. In a multicenter phase II study, we analyzed the feasibility and the efficacy of a maximum of six cycles of i.v. epirubicin plus vinorelbine, followed by oral vinorelbine. We enrolled 30 patients with metastatic breast cancer. Each patient received epirubicin (75 mg/m2 on day 1) and vinorelbine (25 mg/m2 on days 1-8), every 3 weeks, for three cycles or six cycles in case of objective response or stable disease. When a clinical benefit was obtained, patients received oral vinorelbine (60 mg/m2 on days 1-8 every 3 weeks for three cycles). The regimen demonstrated to be active and well tolerated in metastatic breast cancer, and 6-8 months represented the optimal treatment duration. Maintenance therapy with oral vinorelbine was feasible, effective, safe and well accepted by the patients.