Relationship between patient and physician-rated xerostomia and dose distribution to the oral cavity and salivary glands for head and neck cancer patients after radiotherapy.

Introduction: Xerostomia is a frequent complication after curative intended radiotherapy (RT) for head and neck squamous cell carcinoma (HNSCC). Assessment of xerostomia is commonly done by the physician. The aim of this study is to investigate the relation between patient and physician-rated xerostomia and to predict the degree of xerostomia from patients with self-reported xerostomia based on delivered doses to the oral cavity, parotid, and submandibular glands. Material and methods: During a 2-year period, consecutive HNSCC patients attending the follow-up clinic were included. All included patients had self-reported xerostomia, and completed the disease-specific EORTC QLQ-H&N35 questionnaire. The physician assessed the degree of xerostomia with the DAHANCA toxicity scale and was blinded for the EORTC score. Oral cavity, parotid, and submandibular glands (OAR) were delineated on the planning CT according to international guidelines. DVH were extracted from treatment plans. Logistic regression tested the relation between mean doses, patient characteristics, and xerostomia scores. Differences between DVH values and scoring of xerostomia were analyzed with a Kruskal-Wallis test. The relation between xerostomia and dose distributions was further investigated using principal component analysis (PCA). Results: In total, 109 patients were included in the study. A weak correlation was seen between patient and physician-rated toxicity (p = .001), however, in general patients reported more toxicity than physicians. For EORTC score ≥2, the multi-variable analysis was significant for doses to the oral cavity, tobacco status and use of xerogenic medication. Neither the DVH analysis nor the PCA found any clear distinction between xerostomia scores for EORTC or DAHANCA and investigated OARs. Conclusion: Patients tended to report higher scores of xerostomia than the physician. PCA indicated a complex relation between doses to the OAR and xerostomia scores, showing e.g., that reducing doses in one organ was on the expense of increased dose to another organ.

Loss-of-function mutations in filaggrin gene and malignant melanoma: a case-control study.

BACKGROUND: Loss-of-function mutations in filaggrin gene (FLG) have been suggested to increase the susceptibility of skin malignancies due to reduced levels of epidermal filaggrin and its degradation products, urocanic acid, which may be protective against ultraviolet irradiation. OBJECTIVE: We aimed to investigate the association between FLG mutation status and the occurrence of malignant melanoma (MM) in Danish adults. METHODS: The prevalence of FLG mutations in a sample of MM biopsies was compared with a FLG-genotyped cohort from two general population studies. Pearson's chi-squared and Fisher's exact tests were used to compare the two groups. RESULTS: A total of 867 MM biopsies and 9965 general population controls were genotyped, respectively. In the MM sample, two (0.23%) individuals were homozygous and 80 (9.4%) were heterozygous mutation carriers. In the general population controls, the prevalence of FLG mutations was 18 (0.18%) and 835 (8.4%) for homozygous and heterozygous mutations, respectively. Fisher's exact test and Pearson's chi-squared test yielded non-significant P-values when the groups were compared. CONCLUSION: FLG mutation was not associated with MM in the studied populations. This finding indicates that epidermal deficiency of filaggrin and its degradation products does not influence the risk of MM significantly.

Filaggrin loss-of-function mutations, atopic dermatitis and risk of actinic keratosis: results from two cross-sectional studies.

BACKGROUND: Common loss-of-function mutations in filaggrin gene (FLG) represent a strong genetic risk factor for atopic dermatitis (AD). Homozygous mutation carriers typically display ichthyosis vulgaris (IV) and many have concomitant AD. Previously, homozygous, but not heterozygous, filaggrin gene mutations have been associated with squamous cell carcinomas. OBJECTIVE: The first objective was to examine the association between FLG mutations and actinic keratosis (AK). The second objective was to investigate the occurrence of AK in patients with IV and AD, respectively. METHODS: FLG mutation status in patients with AK was compared with controls from the general population. Furthermore, based on nationwide data from Danish registers, we compared the risk of AK in patients with IV, AD and psoriasis, respectively. RESULTS: The prevalence of homozygous FLG mutations was significantly higher in the AK group (n = 4, 0.8%) in comparison with the control group (n = 18, 0.2%), whereas the prevalence of heterozygous FLG mutations was lower. In hospital registry data, patients with AD exhibited an increased risk of AK than did psoriasis controls (adjusted OR 1.46; [95% CI 1.12-1.90]), whereas no difference in risk was observed between patients with IV and AD. CONCLUSIONS: This study indicates an increased susceptibility to AK in individuals with homozygous, but not heterozygous, FLG mutations and in patients with AD compared to psoriasis. Whether a reduction or absence of epidermal filaggrin could contribute to the susceptibility to AK in patients with IV and AD is unknown and additional research is needed to further explore this relationship.

Amanitin toxicosis in two cats with acute hepatic and renal failure.

Amanitin is a toxic cyclopeptide present in several species of poisonous mushrooms. Amanitin toxicosis was diagnosed in 2 cats from separate premises. Both cats initially had lethargy and vomiting, and they rapidly developed depression and neurological signs over 24-48 hours. Marked elevation of alanine aminotransferase was the primary finding, with subsequent serum chemistry values compatible with hepatic and renal failure. Histopathological findings consisted of submassive to massive acute hepatic necrosis, renal proximal tubular epithelial necrosis, and foci of necrosis and inflammation in the gastrointestinal tract. Amanitin exposure was confirmed postmortem by detection of α-amanitin in the kidney by liquid chromatography-mass spectrometry. A similar clinical course and pathological changes are reported in human and canine amanitin intoxication; however, gastrointestinal lesions are not typically described.

Visceral leishmaniasis diagnosed in a patient with MALT lymphoma.

We report a case of visceral leishmaniasis in a 66-year-old female with a history of MALT lymphoma in the gastrointestinal tract. The patient presented with major hemorrhage per rectum and perforation of the small intestine. Due to unexplained decreasing platelets, lymphoma bone marrow involvement was suspected and bone marrow examination was performed. Surprisingly, Leishman-Donovan bodies were detected. The low platelet count, caused by the combination of MALT lymphoma and visceral leishmaniasis, appears to have aggravated the symptoms of the intestinal lymphoma. Leishmaniasis should be suspected even among asymptomatic patients with immune compromising illnesses and a travel history to areas where leishmaniasis is endemic.

Esophageal stenting for treatment of refractory benign esophageal strictures in dogs.

BACKGROUND: Benign esophageal strictures can recur despite multiple dilatation procedures and palliative management can be challenging. OBJECTIVE: To describe the technique and determine the outcome of esophageal stenting for treatment of refractory benign esophageal strictures (RBES) in dogs. ANIMALS: Nine dogs with RBES. METHODS: Retrospective review of records for dogs with RBES. Indwelling intraluminal esophageal stents were placed transorally with endoscopy, fluoroscopic guidance, or both. Follow-up information was obtained via medical record or telephone interview. RESULTS: Nine dogs had 10 stents placed including biodegradable stents (BDS) (6/10), self-expanding metallic stents (SEMS) (3/10), and a self-expanding plastic stent (SEPS) (1/10). All dogs had short-term improved dysphagia. Complications included ptyalism, apparent nausea, gagging, vomiting, or regurgitation (8/9), confirmed recurrence of stricture (6/9), stent migration (3/9), stent shortening (1/9), megaesophagus (1/9), incisional infection (1/9), and tracheal-esophageal fistula (1/9). Eight of 9 dogs required intervention because of the complications of which 4 of 8 dogs were eventually euthanized because of stent-related issues. One dog was lost to follow-up examination. CONCLUSIONS AND CLINICAL IMPORTANCE: Findings suggest that esophageal stent placement was safe and technically effective, but unpredictably tolerated in dogs with RBES. If a stent is placed, dogs should be monitored carefully for stent migration, dissolution of absorbable stents, and recurrence of strictures.

Ultralow emittance, multi-MeV proton beams from a laser virtual-cathode plasma accelerator.

The laminarity of high-current multi-MeV proton beams produced by irradiating thin metallic foils with ultraintense lasers has been measured. For proton energies >10 MeV, the transverse and longitudinal emittance are, respectively, <0.004 mm mrad and <10(-4) eV s, i.e., at least 100-fold and may be as much as 10(4)-fold better than conventional accelerator beams. The fast acceleration being electrostatic from an initially cold surface, only collisions with the accelerating fast electrons appear to limit the beam laminarity. The ion beam source size is measured to be <15 microm (FWHM) for proton energies >10 MeV.