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Hepatozoon spp. is the causative agent of a vector-borne parasitic disease in many animal species. In felids, Hepatozoon felis, Hepatozoon canis and Hepatozoon silvestris have been molecularly isolated. Hepatozoonosis usually causes asymptomatic infections in domestic cats, but clinical cases have recently been reported in Europe. We describe the first Italian case of hepatozoonosis in a cat with an unusual presentation. An 11-year-old neutered European shorthair cat was urgently hospitalized for intestinal intussusception. Hematology, biochemistry, FIV-FeLV tests, blood smears and molecular investigation targeting the 18S rRNA gene of Hepatozoon spp. were performed on blood samples; in addition, histological and molecular investigations were performed to analyze surgical samples to identify Hepatozoon infection. Hepatozoon gamonts were detected in granulocytes in the blood smear, and Hepatozoon spp. DNA was confirmed by PCR on blood. The intussusception was caused by a sessile endoluminal nodule that was surgically removed. Histologically, many elements referring to parasitic tissue forms were identified in the intestinal cells, and then the specimens were molecularly confirmed to harbor H. silvestris . This is the first description of symptomatic hepatozoonosis in a domestic cat in Italy. Hepatozoon silvestris has been described in wild felids, which are usually resilient to the infection, whereas the domestic cat seems to be more susceptible. Indeed, H. silvestris in cats usually presents tropism for skeletal muscle and myocardium with subsequent clinical manifestations. This is the first description of a domestic cat with H. silvestris localized in the intestinal epithelium and associated with intussusception. Graphical abstract

The tiger ( Panthera tigris ), which is the largest living feline, is waging a grim battle for survival, with only less than 2300 left out in the wild. Information on the cause of death of every single tiger is important, as it will help in devising suitable conservation measures. However, most of the deaths reported in the wild are due to ‘unknown etiology’ and reports on infectious causes are almost absent. The present paper describes the death of a wild tiger, associated with infection of the submucosal hookworm of large felines, Galoncus perniciosus . Necropsy revealed that the small intestinal serosa was congested with extensive paint-brush haemorrhages for the most part. There were about 27 intestinal nodules, each measuring about 1.5 cm in diameter, containing haemorrhagic exudate and parasites identified as G. perniciosus . The serosa also showed clear ante-mortem circumferential tears in seven places; some of them were superficial, limited to the serosa, while others extended into the muscularis mucosa. The possibility of death due to septicaemia or neurogenic shock resulting from galoncosis is discussed based on the circumstances and distinct necropsy lesions. The implications of such infectious diseases on the tiger conservation strategy are also discussed.

We comprehensively estimated the prevalence of goiter and thyroid nodules (TNs) before and after the implementation of the Universal Salt Iodization (USI) program in mainland China and provided information for creating effective health policies. PubMed, Google Scholar, CNKI, Chinese Wanfang and Chongqing VIP databases were searched for relevant studies from Jan 1985 to Feb 2014. Data from eligible citations were extracted by two independent reviewers. All analyses were performed with Stata 11.0 and SPSS 17.0. Eligible articles (N = 31; 4 in English and 27 in Chinese) included 52 studies (15 about goiter rates made before 1996 and 14 afterwards, and 23 about TNs). Our meta-analysis suggests a pooled prevalence for goiter before and after 1996 and for TNs of 22.8% (95% CI: 15.3%, 30.3%), 12.6% (95% CI: 9.4%, 15.8%) and 22.7% (95% CI: 18.3%, 27.0%), respectively. Egger's test of three independent categories revealed no evidence of publication bias (p = 0.101, 0.148 and 0.113, respectively). The prevalence of goiter was reduced by almost half after 1996 in mainland China, so the USI program was considered beneficial. However, subgroup analysis suggests that both insufficient and excess iodine may be associated with goiter. The prevalence of goiter and TNs increased significantly after 2002, suggesting a risk of excessive iodine intake. Thus, salt iodization standardizations should be set according to local conditions.

Background The thyroid-gut axis refers to the intricate relationships among the gut, intestinal microbiota, and thyroid gland, and it is speculated to play an important role in the development of thyroid diseases. The aim of this study was to identify the differentiated bacteria in the intestinal microbiota associated with papillary thyroid carcinoma (PTC) and benign thyroid nodules (BTNs) to offer potential avenues for further exploration and therapeutic interventions. Methods Faecal microbiotas of 197 subjects (73 from subjects with BTNs, 62 from subjects with PTC, and 62 from sex- and age-matched controls) were characterized by sequencing the V3-V4 region of 16 S rDNA using the Illumina NovaSeq 6000 platform. Microbiomics and machine learning-assisted approaches were used to identify the PTC-/BTN-associated intestinal microbial indicators. Results Compared with the abundance of coabundant groups (CAGs) in the PTC, BTN, and control groups, the abundance of two Genus-CAGs consisting of butyrate producers, such as Blautia , Lachnoclostridium , Lachnospiraceae _unclassified, Eisenbergiella , Flavonifractor and Hungatella , was lower in the PTC group than in the control group. In particular, both ANCOM-BC2 and Wilcoxon rank-sum test results consistently demonstrated significant enrichment of the butyrate-producing genera Oscillibacter , Coprobacter , and Colidextribacter in both BTN patients and healthy controls. The majority of discriminatory amplicon sequence variants (ASVs) that could discriminate PTCs from controls, as well as from BTNs, were from Prevotella, Streptococcus, Bacteroides, and butyrate-producing groups, such as the Oscillibacter, Lachnospiraceae, and Christensenellaceae (R7) groups. ASV indicators from Prevotella and Streptococcus were most abundant in the PTC group, and those from Bacteroides and the butyrate-producing/-promoting group were least abundant in the PTC group. Additionally, the ASVs that could discriminate the BTN group from the control group, as well as PTC group included other butyrate-producing groups, the Clostridium_sensu_stricto group, and the Eubacterium _ siraeum group. Conclusions This study demonstrates that dysbiosis linked to thyroid nodules is marked by a substantial decline in intestinal butyrate-producing and butyrate-promoting taxa. Future work to confirm these results should include shotgun metagenomic sequencing paired with quantitative analyses of gene abundance and expression to fully ascertain the functional implications.

Our aim was to investigate utility of indocyanine green (ICG) and autofluorescence (AF) imaging in detection of small bowel primary and metastatic carcinoids. Using Institutional Review Board approval, ICG and AF imaging of small bowel carcinoids was performed. Imaging findings were prospectively recorded in operating room and compared with conventional imaging, surgical exploration and pathologic findings. There were 16 patients with 23 primary small bowel tumors, 27 mesenteric lymph nodes, 36 liver metastases and 2 peritoneal nodules. Carcinoid tumors exhibited brighter AF signals compared to background. AF imaging was superior to both DOTATATE PET and surgeon inspection/palpation in demonstrating small bowel primaries. Utility for metastatic lymph nodes and peritoneal metastases was limited. Superficial liver metastases exhibited brighter fluorescence compared to background on both ICG and AF imaging. This is the largest study assessing utility of near-infrared fluorescence imaging in detection of small bowel carcinoids. Our results show promise in the utilization fluorescence imaging to detect occult primary tumors and superficial liver metastases. •Autofluorescence imaging detects small bowel carcinoid tumors with a high accuracy.•Autofluorescence imaging outperforms preoperative imaging in detecting small bowel cacinoids.•Autofluorescence imaging aids in identifying occult primary tumors during surgery.•Autofluorescence imaging has a limited value in detecting lymph node metastases.•Fluorescence imaging may be used to guide resection of superficial liver metastases.

Abstract Introduction/Objective Intussusception is uncommon in adults. When it occurs it is usually secondary to a mass lesion. The purpose of this report is to highlight an unusual cause of intussusception. Methods/Case Report A 48-year-old female presented with right lower abdominal pain, nausea, vomiting, and bloating. She didn’t have a bowel movement in 3-4 days. CT of the abdomen and pelvis demonstrated long segment small bowel intussusception in the right abdomen with a lead point mass. The patient subsequently underwent surgical resection. Grossly the specimen consisted of a 30cm segment of small bowel remarkable for two mucosal nodules measuring 1.9 cm and 1.0 cm in greatest dimension. Microscopically the nodules were composed of sheets of discohesive epithelioid cells with marked nuclear pleomorphism and prominent nucleoli, underlying the normal mucosa. Immunohistochemical studies revealed that the tumor cells to be positive for SOX-10 and MART-1and negative for pan-cytokeratin and DOG1. Diagnosis of malignant melanoma was rendered. Results (if a Case Study enter NA) NA Conclusion Intussusception due to malignant / metastatic melanoma is rare but should be on the differential for patients with symptoms of small bowel obstruction and intussusception with a lead point mass.

PurposeTrimethylamine N-oxide (TMAO), a gut microbiome–derived metabolite, and its precursors (carnitine, choline, betaine) have not been fully examined in relation to thyroid cancer (TC) risk. The aim of this study was to assess the value of TMAO and its precursors in diagnosis of benign and malignant thyroid nodules.MethodsIn this study, high-performance liquid chromatography-tandem mass spectrometry was utilized to measure the levels of plasma TMAO and its precursors (choline, carnitine, and betaine) in 215 TC patients, 63 benign thyroid nodules (BTN) patients and 148 healthy controls (HC). The distribution of levels of TMAO and its precursors among the three groups were compared by the Kruskal–Wallis test. Receiver operating characteristic curve (ROC) analysis was performed to evaluate the sensitivity, specificity, and the predictive accuracy of single and combined biomarkers.ResultsIn comparison to HC, TC showed higher levels of TMAO and lower levels of its precursors (carnitine, choline, and betaine) (all P < 0.001). Plasma choline (P < 0.01) and betaine (P < 0.05) were declined in BTN than HC. The levels of carnitine (P < 0.001) and choline (P < 0.05) were significantly higher in BTN than that in TC group. Plasma TMAO showed lower levels in TC with lymph node metastasis (101.5 (73.1–144.5) ng/ml) than those without lymph node metastasis (131 (84.8–201) ng/ml, P < 0.05). Combinations of these four metabolites achieved good performance in the differential diagnosis, with the area under the ROC curve of 0.703, 0.741, 0.793 when discriminating between TC and BTN, BTN and HC, TC and HC, respectively.ConclusionPlasma TMAO, along with its precursors could serve as new biomarkers for the diagnosis of benign and malignant thyroid nodules.

Objective: Thyroid disease has been reported to associate with gut microbiota, but the effects of thyroid cancer and thyroid nodules on the oral microbiota are still largely unknown. This study aimed to identify the variation in salivary microbiota and their potential association with thyroid cancer and thyroid nodules.Methods: We used 16S rRNA high-throughput sequencing to examine the salivary microbiota of thyroid cancer patients (n = 14), thyroid nodules patients (n = 9), and healthy controls (n = 15).Results: The alpha-diversity indices Chao1 and ACE were found to be relatively higher in patients with thyroid cancer and thyroid nodules compared to healthy controls. The beta diversity in both the thyroid cancer and thyroid nodules groups was divergent from the healthy control group. The genera Alloprevotella, Anaeroglobus, Acinetobacter, unclassified Bacteroidales, and unclassified Cyanobacteriales were significantly enriched in the thyroid cancer group compared with the healthy control group. In contrast, the microbiome of the healthy controls was mainly composed of the genera Haemophilus, Lautropia, Allorhizobium Neorhizobium Pararhizobium Rhizobium, Escherichia Shigella, and unclassified Rhodobacteraceae. The thyroid nodules group was dominated by genre uncultured Candidatus Saccharibacteria bacterium, unclassified Clostridiales bacterium feline oral taxon 148, Treponema, unclassified Prevotellaceae, Mobiluncus, and Acholeplasma. In contrast, the genera unclassified Rhodobacteraceae and Aggregatibacter dominated the healthy control group. The study also found that clinical indicators were correlated with the saliva microbiome.Conclusion: The salivary microbiota variation may be connected with thyroid cancer and thyroid nodules.

Thyroid nodules are found in nearly half of the adult population. Accumulating evidence suggests that the gut microbiota plays an important role in thyroid metabolism, yet the association between gut microbiota capacity, thyroid nodules, and thyroid function has not been studied comprehensively. We performed a gut microbiome genome-wide association study in 196 patients with thyroid nodules and 283 controls by using whole-genome shotgun sequencing. We found that participants with high-grade thyroid nodules have decreased number of gut microbial species and gene families compared with those with lower grade nodules and controls. There are also significant alterations in the overall microbial composition in participants with high-grade thyroid nodules. The gut microbiome in participants with high-grade thyroid nodules is characterized by greater amino acid degradation and lower butyrate production. The relative abundances of multiple butyrate producing microbes are reduced in patients with high-grade thyroid nodules and the relative abundances of L-histidine metabolism pathways are associated with thyrotropin-releasing hormone. Our study describes the gut microbiome characteristics in thyroid nodules and a gut-thyroid link and highlight specific gut microbiota as a potential therapeutic target to regulate thyroid metabolism.

Animal models for human colorectal cancer recapitulate multistep carcinogenesis that is typically initiated by activation of the Wnt pathway. Although potential roles of both genetic and environmental modifiers have been extensively investigated in vivo, it remains elusive whether epithelial cells definitely require interaction with stromal cells or microflora for tumor development. Here we show that tumor development could be simply induced independently of intestinal microenvironment, even with WT murine primary intestinal cells alone. We developed an efficient method for lentiviral transduction of intestinal organoids in 3D culture. Despite seemingly antiproliferative effects by knockdown of adenomatous polyposis coli (APC), we managed to reproducibly induce APC -inactivated intestinal organoids. As predicted, these organoids were constitutively active in the Wnt signaling pathway and proved tumorigenic when injected into nude mice, yielding highly proliferative tubular epithelial glands accompanied by prominent stromal tissue. Consistent with cellular transformation, tumor-derived epithelial cells acquired sphere formation potential, gave rise to secondary tumors on retransplantation, and highly expressed cancer stem cell markers. Inactivation of p53 or phosphatase and tensin homolog deleted from chromosome 10, or activation of Kras, promoted tumor development only in the context of APC suppression, consistent with earlier genetic studies. These findings clearly indicated that genetic cooperation for intestinal tumorigenesis could be essentially recapitulated in intestinal organoids without generating gene-modified mice. Taken together, this in vitro model for colon cancer described herein could potentially provide unique opportunities for carcinogenesis studies by serving as a substitute or complement to the currently standard approaches.