Tumor-infiltrating lymphocytes play an important role in cell-mediated immune destruction of cancer cells and tumor growth control. We investigated the heterogeneity of immune cell infiltrates between primary non-small cell lung carcinomas (NSCLC) and corresponding metastases. Formalin-fixed, paraffin-embedded primary tumors and corresponding metastases from 34 NSCLC patients were analyzed by immunohistochemistry for CD4, CD8, CD11c, CD68, CD163 and PD-L1. The percentage of positively stained cells within the stroma and tumor cell clusters was recorded and compared between primary tumors and metastases. We found significantly fewer CD4(+) and CD8(+) T cells within tumor cell clusters as compared with the stromal compartment, both in primary tumors and corresponding metastases. CD8(+) T cell counts were significantly lower in metastatic lesions than in the corresponding primary tumors, both in the stroma and the tumor cell islets. Of note, the CD8/CD4 ratio was significantly reduced in metastatic lesions compared with the corresponding primary tumors in tumor cell islets, but not in the stroma. We noted significantly fewer CD11c(+) cells and CD68(+) as well as CD163(+) macrophages in tumor cell islets compared with the tumor stroma, but no difference between primary and metastatic lesions. Furthermore, the CD8/CD68 ratio was higher in primary tumors than in the corresponding metastases. We demonstrate a differential pattern of immune cell infiltration in matched primary and metastatic NSCLC lesions, with a significantly lower density of CD8(+) T cells in metastatic lesions compared with the primary tumors. The lower CD8/CD4 and CD8/CD68 ratios observed in metastases indicate a rather tolerogenic and tumor-promoting microenvironment at the metastatic site.

Risk factors for the development of reflux disease include increased gastric acid production, prolonged gastric emptying, restricted oesophageal clearance, reduced saliva secretion, increased intraabdominal pressure and sphincter insufficiency. Above all, acid, pepsin, bile salts and other gastroduodenal proteins cause mucosal irritation. Particularly, the combination of acid and pepsin tends to lead to mucosal damage, whereas the laryngopharyngeal mucosa is much more sensitive than the oesophageal mucosa due to a lack of defence mechanisms. 1,2 Gastro-oesophageal reflux (GER) and laryngopharyngeal reflux (LPR) are two different clinical entities, and a fundamental distinction needs to be made. GER often occurs at night and has classic reflux symptoms such as heartburn, acid regurgitation and retrosternal pain.In contrast, LPR occurs mostly during daytime and causes non-specific symptoms such as hoarseness, globus sensation, chronic throat clearing and increased mucus. 3 Nevertheless, GER and LPR can occur simultaneously and cause similar symptoms. 4 A correlation between various clinical pictures and GER has already been established. 5 These include reflux oesophagitis, oesophageal strictures, Barrett oesophagus and Barrett carcinoma. However, data for LPR are less clear.Various medical conditions seen on a daily basis such as chronic laryngopharyngitis, chronic sinusitis, bronchial asthma, pulmonary fibrosis and recurrent otitis media are associated with LPR. 6 Today, oesophago-gastro-duodenoscopy and impedance pH monitoring are the gold standard to assess GER. 5 In contrast, LPR is often diagnosed by clinical signs and symptoms and/or a trial of proton pump inhibitor (PPI) therapy. A few validated methods already exist to detect and quantify LPR, namely the reflux symptom index (RSI), the reflux finding score (RFS) and oropharyngeal pH monitoring (PHM). The latter was first described in 2009 and has been validated by various research groups. [7][8][9] Meanwhile, its reliability and reproducibility was proven to be high for extraoesophageal reflux assessment. [10][11][12]

In this study, we report the first case of reptile-associated maxillary sinusitis due to Salmonella enterica subspecies diarizonae in a snake handler and the third case of salmonella-associated sinusitis worldwide. The case highlights the potential of respiratory transmission and atypical salmonellosis presentations.

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Gentamicin is a widely used antibiotic for the treatment of gram-negative bacterial infections; however, its use often results in significant and permanent hearing loss. Hearing loss resulting from hair cell (HC) degeneration affects millions of people worldwide, and one major cause is the loss of sensory HCs in the inner ear due to aminoglycoside exposure. Strategies to overcome the apparently irreversible loss of HCs in mammals are crucial for hearing protection. Here, we report that the somatostatin analog pasireotide protects mouse cochlear HCs from gentamicin damage using a well-established in vitro gentamicin-induced HC loss model and that the otoprotective effects of pasireotide are due to Akt up-regulation via the PI3K–Akt signal pathway activation. We demonstrate active caspase signal in organ of Corti (OC) explants exposed to gentamicin and show that pasireotide treatment activates survival genes, reduces caspase signal, and increases HC survival. The neuropeptide somatostatin and its selective analogs have provided neuroprotection by activating five somatostatin receptor (SSTR1–SSTR5) subtypes. Pasireotide has a high affinity for SSTR2 and SSTR5, and the addition of SSTR2- and SSTR5-specific antagonists leads to a loss of protection. The otoprotective effects of pasireotide were also observed in a gentamicin-injured animal model. In vivo studies have shown that 13 days of subcutaneous pasireotide application prevents gentamicin-induced HC death and permanent hearing loss in mice. Auditory brainstem response analysis confirmed the protective effect of pasireotide, and we found a significant threshold shift at all measured frequencies (4, 8, 16, 24, and 32 kHz). Together, these findings indicate that pasireotide is a novel otoprotective peptide acting via the PI3K–Akt pathway and may be of therapeutic value for HC protection from ototoxic insults.

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Background: Laryngopharyngeal reflux (LPR) can display a variety of symptoms, and upper endoscopy is occasionally used for its investigation. The aim of the present study was to determine the value of transnasal esophagoscopy (TNE) in the workup of LPR. Methods: In 200 consecutive patients with suspected LPR, reflux symptom index (RSI), reflux finding score (RFS), oropharyngeal pH-monitoring (PHM) and transnasal esophagoscopy (TNE) were carried out and rated according to the Horvath Score. Results: In the investigation of LPR, TNE showed a sensitivity, specificity and accuracy of 96%, 85% and 95%, respectively. The most common pathologic TNE findings in LPR patients were an insufficient cardia, hiatal hernia, lymphoid follicles and visible reflux. Conclusions: TNE is a supportive method in the workup of LPR, which can display the underlying pathology and directly affect therapeutic decisions.

Background: Laryngopharyngeal reflux (LPR) is a prevalent disorder. The aim of the present retrospective cohort study was to evaluate oropharyngeal pH-monitoring using a novel scoring system for LPR. Methods: In a total of 180 consecutive patients with possible LPR, reflux symptom index (RSI), reflux finding score (RFS), oropharyngeal pH-monitoring and transnasal esophagoscopy were carried out for further investigation. Results: In our series, 99 (55%) patients had severe LPR, 29 (16%) cases presented with moderate and 23 (13%) with mild severity, 9 (5%) subjects revealed neutral values, and 7 (4%) individuals were alkaline, while 13 (7%) patients had no LPR. In detecting LPR, the sensitivity, specificity and accuracy of oropharyngeal pH-monitoring was 95%, 93% and 94%, respectively. Conclusion: Oropharyngeal pH-monitoring is a reliable tool in the assessment of LPR, but the pH graphs have to be precisely analyzed and interpreted in context with other validated diagnostic tests.