Activity of cabozantinib in radioresistant brain metastases from renal cell carcinoma: two case reports

Renal cell carcinoma represents 3–5% of adult malignant tumors. Metastases are found in 30–40% of patients and brain metastases occurred in more than 10% of them. Despite significant progress in medical treatm...

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ILC2s — resident lymphocytes pre-adapted to a specific tissue or migratory effectors that adapt to where they move?

Ronald N Germain | Yuefeng Huang

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Toxicological and Biochemical Analyses of an Autopsy Case Involving Oral Overdose of Multiple Antidiabetic and Antihypertensive Drugs

Oral antidiabetics can cause fatal hypoglycemia; although they can be chemically identified and quantified, biochemical investigations are important for assessing the biological consequences of an overdose. Such cases of overdose involving oral antidiabetics may involve other drugs for treating lifestyle-related diseases, particularly antihypertensives. Here, we report a toxicological and biochemical investigation of drugs and biochemical profiles in a fatal overdose involving multiple oral antidiabetics and antihypertensives. A 55-year-old woman died about 2 days after the ingestion of around 110 tablets of antidiabetics and antihypertensives that had been prescribed for her husband. A forensic autopsy and histological analysis demonstrated no evident pathology as the cause of death. A toxicological analysis suggested hypoglycemia and an overdose of antihypertensives as well as the retention of antidiabetics and diuretics in the pericardial fluid. A relatively low pericardial amlodipine concentration was observed, which may have been the result of its long half-life (slower distribution and reduction rate) and/or possible affinity with the myocardium. In addition, a biochemical analysis indicated hypoglycemia, without increased serum insulin and C-peptide, but with increased glucagon levels, as the possible influence of glibenclamide overdose. These observations suggest the usefulness of a combination of toxicological and biochemical analyses in postmortem investigations involving a fatal overdose of such drugs.

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Nationwide analysis of unplanned 30‐day readmissions after transsphenoidal pituitary surgery

Background

Transsphenoidal pituitary surgery has evolved into a safe procedure with shorter hospitalizations, yet unplanned readmissions remain a quality measure for which there is a paucity of data. We sought to examine rates, timing, etiologic factors, and costs surrounding readmission after transsphenoidal pituitary surgery.

Methods

The Nationwide Readmissions Database (NRD) was queried for patients who underwent transsphenoidal pituitary between January 2013 and November 2013. Patient, procedure, admission, and hospital‐level characteristics were compared for patients with and without unplanned 30‐day readmission. Multivariate logistic regression was used to identify readmission predictors. A total of 8546 patients were included in this retrospective study.

Results

A total of 8546 patients with a median age of 54 years and female predominance were identified, with 742 patients experiencing at least 1 unplanned readmission within 30 days of index admission. Hypertension, hypothyroidism, diabetes, and obesity were common comorbidities among readmitted patients. Readmission was most frequently because of nervous system complications, followed by neurohypophyseal or electrolyte disorders, cerebrospinal fluid leak, hemorrhage, and meningitis. Median length and cost of stay of index admission was greater in the readmission group (p < 0.001). Fluid and electrolyte disorders as well as neurologic disease (most commonly epilepsy or convulsions) present on initial admission were predictive of length of initial stay and readmission (p < 0.001). Median readmission cost was $7723 and was expected to occur within 7 days.

Conclusion

Approximately 8.7% of patients undergoing transsphenoidal pituitary surgery experience an unplanned readmission within 30 days of discharge. Risk factors identified should be considered to reduce preventable readmissions and identify medically complex patients.

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Effect of elderly status on postoperative complications in patients with sinonasal cancer

Background

Elderly patients with multiple comorbidities may be at higher risk of postoperative complications. With an increasingly aging population, more data assessing for predisposing factors are needed in this at‐risk group. In this study, we analyzed the effect of elderly status on relative comorbidities and complications of sinonasal cancer (SNC) patients receiving surgery.

Methods

A retrospective database analysis was performed using cases from the Nationwide Inpatient Sample (NIS) from 2003 to 2012. Patients with a diagnosis of malignant neoplasm of the nasal cavity or paranasal sinuses, who received surgery for sinonasal malignancy, including neck dissections, were selected. Demographics of interest included age, sex, race, type of admission, mean length of stay, and median hospital charges. Elderly and nonelderly patients were compared for differences in rates of acute medical complications, acute surgical complications, and relevant procedures during hospitalization.

Results

Of the 920 cases identified in the NIS, 382 (41.5%) were elderly (≥65 years). Cases of SNC were more frequently seen in males than females (p < 0.001). Elderly patients had significantly higher comorbidity rates compared with nonelderly patients, which included congestive heart failure, hypertension, diabetes, chronic pulmonary disease, and chronic renal failure (p < 0.001 for all). Elderly patients more frequently had postoperative cardiac complications (6.0% vs 0.5%, p < 0.001), but this finding was not statistically significant on multivariate analysis when controlling for race, sex, and comorbidities.

Conclusion

Elderly status is not an independent factor for postoperative complications in patients undergoing surgery for sinonasal malignancy.

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The effects of cryotherapy on vocal fold healing in a rabbit model

Objectives/Hypothesis

Cryotherapy has been shown to be a scarless treatment modality for dermal lesions; however, there are limited data addressing the effect of cryotherapy on vocal fold tissue. The aim of this study was to clarify the effectiveness of cryotherapy for prevention of postsurgical vocal fold scarring.

Study Design

Prospective animal study in rabbits.

Methods

The lamina propria of 20 rabbit vocal folds was bilaterally stripped, followed by randomized unilateral cryotherapy. Five larynges were harvested for real‐time polymerase chain reaction (RT‐PCR) analysis at 1 day, 3 days, and 7 days postinjury. The remaining five were harvested for histologic analysis at 3 months. Images of the healing phase were recorded by laryngoscopy. Analyses of RT‐PCR for cyclooxygenase (COX)‐2, interleukin (IL)‐6, collagen I, collagen III, matrix metallopeptidase 1 (MMP1), transforming growth factor β (TGFβ1), α smooth muscle actin (α‐SMA), and hyaluronan synthase 1 (HAS1) were completed. Histological samples were completed for collagen and hyaluronic acid analysis.

Results

RT‐PCR results revealed that higher expressions of HAS1 and MMP1 and lower expressions of COX‐2, IL‐6, collagen I, collagen III, TGFβ1, and α‐SMA were observed, and histological examination showed significantly increased hyaluronic acid, decreased deposition, and more organized configuration of collagen in injury with the cryotherapy cohort compared with the injury cohort.

Conclusions

Cryotherapy can inhibit the inflammatory reaction and simulate a fetal healing environment in extracellular matrix synthesis to regenerate vocal fold tissue with less fibrosis. Histological results showed that cryotherapy achieves a mature healing result with less scar, which tends to return to normal. In summary, the findings of this study suggest that administration of cryotherapy at the time of injury has the potential to minimize vocal fold scarring.

Level of Evidence

NA Laryngoscope, 2018

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Acute inflammatory response to contrast agent aspiration and its mechanisms in the rat lung

Objectives/Hypothesis

Contrast agent (CA) aspiration is an established complication of upper gastrointestinal and videofluoroscopic swallow studies. The underlying molecular biological mechanisms of acute response to CA aspiration in the respiratory organs remain unclear. The aims of this study were to elucidate the histological and biological influences of three kinds of CAs on the lung and to clarify the differences in acute responses.

Study Design

Animal model.

Methods

Eight‐week‐old male Sprague Dawley rats were divided into five groups (n = 6 in each group). Three groups underwent tracheal instillation of one of three different CAs: barium (Ba) sulfate, nonionic contrast agents (NICAs), and ionic contrast agents (ICAs). A control group was instilled with saline and a sham group was instilled with air. All animals were euthanized on day 2 after treatment and histological and gene analysis was performed.

Results

No animal died after CA or control/sham aspiration. Ba caused severe histopathologic changes and more prominent inflammatory cell infiltration in the lungs compared with the two other iodinated contrast agents. Increases in expressions of inflammatory cytokines (tumor necrosis factor [Tnf], interleukin‐1β [Il1b], and interferon‐γ [Ifng]) were observed in Ba aspiration rats, and upregulation of Il1b was seen in ICA aspiration rats. NICA did not cause obvious histologic changes or expressions of inflammatory cytokines and fibrosis‐related genes in the lungs.

Conclusions

Ba caused significantly more acute lung inflammation in a rodent model than did ioinic and nonionic iodinated CAs. Nonionic contrast did not cause any discernible inflammatory response in the lungs, suggesting that it may be the safest contrast for videofluoroscopic swallow studies.

Level of Evidence

NA

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