Thyroid disorders induced by checkpoint inhibitors

Immune checkpoint inhibitors are drugs that inhibit the "checkpoint molecules". Different types of cancer immune checkpoint inhibitors have been approved recently: CTLA-4 monoclonal antibodies (as ipilimumab); anti-PD-1 monoclonal antibodies (as pembrolizumab and nivolumab); and anti-PD-L1 monoclonal antibodies (as atezolizumab, avelumab, and durmalumab). The increased immune response induced by these agents leads to immune-related adverse events (irAEs), that can vary from mild to fatal, according to the organ system and severity. Immune-related endocrine toxicities are thyroid dysfunctions, hypophysitis, adrenal insufficiency, and type 1 diabetes mellitus, and are usually irreversible in 50%. In particular, hypophysitis is the most frequent anti-CTLA-4-antibodies-related irAE, while thyroid abnormalities (as hypothyroidism, thyrotoxicosis, painless thyroiditis, or even "thyroid storm") are more frequently associated with anti-PD-1-antibodies. The combination of anti-CTLA-4-antibodies, with anti-PD-1-antibodies, is associated with about 30% of irAEs. Clinical signs and symptoms vary according to the influenced target organ. Endocrinopathies can often be managed by the treating oncologist. However in more severe cases (i.e. in the presence of insulin-dependent diabetes, adrenal insufficiency, or disorders of gonadal hormones, or severe hyperthyroidism, or hypothyroidism, or long-lasting management of hypophysitis) an endocrinological evaluation, and a prompt therapy, are needed

Carinal resection

Carinal resection is defined as the resection of tracheo-bronchial bifurcation, with or without lung parenchyma resection. It represents one of the most challenging areas of airway resection and reconstruction, basically due to the variability in the location and extent of the lesions. Main indications for this procedure are primary tumours of the carina or the distal trachea or, more frequently, bronchogenic carcinoma with carinal involvement. Very different approaches and reconstruction techniques have been experimentally and clinically described in the last 50 years, with some corner stone procedures in the history of modern thoracic surgery. Despite many technical and oncological difficulties encountered in this field, encouraging results have been reported in recent series, in particular an excellent 5-year survival rate of 50% in pN0 patients suffering form carinal infiltration form lung cancer. Several aspects of the multimodality approach to neoplastic carinal involvement still remain debatable like radio-chemotherapeutic approach instead of the extremely rare left carinal pneumonectomy as well as the role of induction treatments before embarking in such demanding procedures, according to the \uadpathological nodal status

The King–Devick test for sideline concussion screening in collegiate football

AbstractPurposeSports-related concussion has received increasing attention as a result of neurologic sequelae seen among athletes, highlighting the need for a validated, rapid screening tool. The King–Devick (K–D) test requires vision, eye movements, language function and attention in order to perform and has been proposed as a promising tool for assessment of concussion. We investigated the K–D test as a sideline screening tool in a collegiate cohort to determine the effect of concussion.MethodsAthletes (n=127, mean age 19.6±1.2 years) from the Wheaton College football and men's and women's basketball teams underwent baseline K–D testing at pre-season physicals for the 2012–2013 season. K–D testing was administered immediately on the sidelines for football players with suspected head injury during regular games and changes compared to baseline were determined. Post-season testing was also performed to compare non-concussed athletes’ test performance.ResultsConcussed athletes (n=11) displayed sideline K–D scores that were significantly higher (worse) than baseline (36.5±5.6s vs. 31.3±4.5s, p<0.005, Wilcoxon signed-rank test). Post-season testing demonstrated improvement of scores and was consistent with known learning effects (35.1±5.2s vs. 34.4±5.0s, p<0.05, Wilcoxon signed-rank test). Test-retest reliability was analyzed between baseline and post-season administrations of the K–D test resulting in high levels of test-retest reliability (intraclass correlation coefficient (ICC)=0.95 [95% Confidence Interval 0.85–1.05]).ConclusionsThe data show worsening of K–D test scores following concussion further supporting utility of the K–D test as an objective, reliable and effective sideline visual screening tool to help identify athletes with concussion

High circulating N-terminal pro-brain natriuretic peptide and tumor necrosis factor-alpha in mixed cryoglobulinemia

AIM: To evaluate serum levels of N-terminal pro-brain natriuretic peptide (NTproBNP) and tumor necrosis factor alpha (TNF-alpha) in a large series of patients with hepatitis C associated with mixed cryoglobulinemia (MC+HCV).METHODS: Serum NTproBNP and TNF-alpha levels were assayed in 50 patients with MC+HCV, and in 50 sex- and age-matched controls.RESULTS: Cryoglobulinemic patients showed significantly higher mean NTproBNP and TNF-alpha levels than controls (P < 0.001; Mann-Whitney U test). By defining high NTproBNP level as a value higher than 125 pg/mL (the single cut-off point for outpatients under 75 years of age), 30% of MC+HCV and 6% of controls had high NTproBNP (c2, P < 0.01). With a cut-off point of 300 pg/mL (used to rule out heart failure (HF) in patients under 75 years of age), 8% of MC+HCV and 0 controls had high NTproBNP (c2, P < 0.04). With a cut-off point of 900 pg/mL (used for ruling in HF in patients aged 50-75 years; such as the patients of our study), 6% of MC+HCV and 0 controls had high NTproBNP (c2, P = 0.08).CONCLUSION: The study demonstrates high levels of circulating NTproBNP and TNF-alpha in MC+HCV patients. The increase of NTproBNP may indicate the presence of a subclinical cardiac dysfunctio

Glasgow Prognostic Score Class 2 Predicts Prolonged Intensive Care Unit Stay in Patients Undergoing Pneumonectomy

Background. The Glasgow prognostic score (GPS) is an inflammation-based score based on albuminemia and Creactive protein concentration proved to be associated with cancer-specific survival in several neoplasms. The present study explored the immediate postoperative value of the GPS for patients undergoing pneumonectomy for lung cancer. Methods. The value of the GPS preoperatively was studied in 250 patients undergoing pneumonectomy for non-small cell lung cancer (NSCLC). We analyzed overall postoperative complications, pulmonary and cardiac complications, 30-day postoperative death, reoperation for early complications, intensive care unit (ICU) length of stay and total length of hospital stay. Results. Patients with a GPS of 0 and 1 had a mean ICU length of stay of 0.8 days, whereas patients with a GPS of 2 had a mean ICU stay of 5.0 days (p = 0.004). The postoperative mortality rate in patients with a GPS of 2 was much higher than in patients with a GPS of 1 and 2, although it was not statistically significant (p = 0.083). Conclusions. A preoperative GPS of 2 effectively predicts a prolonged ICU stay in patients who undergo pneumonectomy for cancer. The score may be proposed as an easy-to-determine, economical, and fast preoperative tool to plan and optimize ICU admissions after elective pneumonectomy

Resectable IIIA-N2 non-small-cell lung cancer (NSCLC): In search for the proper treatment

Locally advanced non-small cell lung cancer accounts for one third of non-small cell lung cancer (NSCLC) at the time of initial diagnosis and presents with a wide range of clinical and pathological heterogeneity. To date, the combined multimodality approach involving both local and systemic control is the gold standard for these patients, since occult distant micrometastatic disease should always be suspected. With the rapid increase in treatment options, the need for an interdisciplinary discussion involving oncologists, surgeons, radiation oncologists and radiologists has become essential. Surgery should be recommended to patients with non-bulky, discrete, or single-level N2 involvement and be included in the multimodality treatment. Resectable stage IIIA patients have been the subject of a number of clinical trials and retrospective analysis, discussing the efficiency and survival benefits on patients treated with the available therapeutic approaches. However, most of them have some limitations due to their retrospective nature, lack of exact pretreatment staging, and the involvement of heterogeneous populations leading to the awareness that each patient should undergo a tailored therapy in light of the nature of his tumor, its extension and his performance status