APMIS

doi: 10.1111/apm.13154pmid: N/A

Swan, Kristine Zøylner; Madsen, Stine Horskær; Bonnema, Steen Joop; Nielsen, Viveque Egsgaard; Jespersen, Marie Louise

doi: 10.1111/apm.13267pmid: 35951496

The BRAFV600E (BRAF) mutation is present in 40–50% of papillary thyroid carcinomas (PTC) and has been associated with more aggressive clinicopathological characteristics of PTC. The aim of this study was to evaluate different methods for preoperative identification of the BRAF mutation in PTC using cytological and histological specimens. Prospectively collected preoperative cytological clots from patients with suspected PTC were tested with BRAF immunocytochemistry (ICC) and the Cobas Test (PCR). In addition, histological specimens were tested with BRAF immunohistochemistry (IHC) and the Cobas Test. All nodules were histologically examined. Fifty‐three patients were included in the study. Complete mutation testing was available in 32 patients. The main reason for exclusion was insufficient cell content in the cytological specimen. Twenty‐seven nodules were histologically diagnosed as PTC, and 41% (n = 11) of PTCs were BRAF ICC positive. All non‐PTC nodules were negative by BRAF ICC. In 26 nodules, all four BRAF tests were concordant, while discordant test results were found in six nodules. ICC was in accordance with the consensus BRAF status in five of these nodules, while BRAF status was undetermined in one nodule. BRAF ICC showed high concordance with the Cobas Test and a low rate of false negative stain. These results indicate that BRAF ICC may be a feasible method for preoperative detection of the BRAFV600E mutation in patients with PTC.

Istomin, Natalie; Härma, Mari‐Anne; Akhi, Ramin; Nissinen, Antti E.; Savolainen, Markku J.; Adeshara, Krishna; Lehto, Markku; Groop, Per‐Henrik; Koivukangas, Vesa; Hukkanen, Janne; Hörkkö, Sohvi

doi: 10.1111/apm.13268pmid: 35959517

Obesity is associated with low‐grade inflammation and increased systemic oxidative stress. Roux‐en‐Y gastric bypass (RYGB) surgery is known to ameliorate the obesity‐induced metabolic dysfunctions. We aimed to study the levels of natural antibodies in feces, before and 6 months after RYGB surgery in obese individuals with and without type 2 diabetes (T2D). Sixteen individuals with T2D and 14 non‐diabetic (ND) individuals were operated. Total IgA, IgG and IgM antibody levels and specific antibodies to oxidized low‐density lipoprotein (oxLDL), malondialdehyde‐acetaldehyde adducts (MAA adducts), Porphyromonas gingivalis gingipain A hemagglutinin domain (Rgp44) and phosphocholine (PCho) were measured using chemiluminescence immunoassay. Total fecal IgA was elevated, while total IgM and IgG were not affected by the surgery. Fecal natural IgM specific to oxLDL decreased significantly in both T2D and ND individuals, while fecal IgM to Rgp44 and PCho decreased significantly in T2D individuals. A decrease in IgG to MAA‐LDL, Rgp44 and PCho was detected. RYGB surgery increases the levels of total fecal IgA and decreases fecal natural IgG and IgM antibodies specific to oxLDL. Natural antibodies and IgA are important in maintaining the normal gut homeostasis and first‐line defense against microbes, and their production is markedly altered with RYGB surgery.

Huang, Yun; Zhang, Hui; Feng, Juan; Tang, Bo

doi: 10.1111/apm.13271pmid: 35988018

STK11 is a frequently mutated tumor suppressor in lung adenocarcinoma (LUAD). STK11 mutations also lead to dramatic changes in the tumor microenvironment. Studies have shown that strengthening the killing effect of NK cells is vital for effective cancer treatment. Nonetheless, the mechanism of STK11 mutation in modulating the killing effect of NK cells on LUAD cells remains unclear. The expression of STK11, Ki67, and IFN‐γ in tumor tissues was evaluated by immunohistochemistry. The contents of T cells, NK cells, and macrophages were analyzed by immunofluorescence assay. The expression of IL2, IL6, and IFN‐γ was detected by ELISA. STK11 expression in LUAD cell line was evaluated by qRT‐PCR. CCK‐8 and colony formation assay were used to measure proliferative ability of LUAD cells and the viability of NK cells. Flow cytometry was utilized to analyze cell apoptosis and NK cell content. Transwell assay was utilized to measure the chemotactic capability of NK cells. In vivo experiments validated the effect of abnormal expression of STK11 on tumor growth. LUAD patients with STK11 mutation had a high tumor proliferative ability. Forced expression of STK11 could substantially constrain the proliferation of LUAD cells and induce cell apoptosis. In addition, STK11 deletion significantly reduced the infiltration level of NK cells and inhibited the viability and chemotactic ability of NK cells as well as their killing effect on LUAD cells. In vivo animal experiment results demonstrated that STK11 deletion significantly reduced NK cell infiltration and promoted LUAD tumor growth. This study revealed the mechanism of STK11 mutation regulating NK cytotoxicity and promoting tumor development, providing scientific basis for the exploration of STK11‐related LUAD therapeutic targets and theoretical reference for developing new NK cell‐based immunotherapy.

Hertz, Frederik Boetius; Nielsen, Karen Leth; Olsen, Markus Harboe; Ebdrup, Søren Røddik; Nielsen, Christina; Kirkby, Nikolai Soren; Frimodt‐Møller, Niels; Møller, Kirsten

doi: 10.1111/apm.13263pmid: 35851968

Denmark has experienced an increase in the proportion of invasive vancomycin‐resistant Enterococcus faecium (VRE) since 2002 (e.g. <4% in 2015, 7.1% in 2017 and 12% in 2018). At Rigshospitalet, we employ active screening at departments with high prevalence or in case of outbreaks. This includes the collection of rectal swabs specifically for VRE screening. Our purpose was to describe the carrier prevalence of vancomycin‐resistant enterococci among acute patients admitted to the Neurointensive Care Unit, Department of Neuroanaesthesiology, Rigshospitalet, Copenhagen, Denmark (NICU). Between April 2018 and January 2019, we investigated 99 consecutive rectal swabs from patients admitted to NICU. The primary outcome was prevalence of VRE carriage. The median age was 64 years (range 23–87) and gender was equally distributed (Female = 47, Male = 46). 26 (28%) had previously been admitted within 179 days and 67 patients (72%) had no hospital admissions within 180 days prior to the admission to NICU. Of the 93 rectal swabs, 2 (2%, 95% CI 0.26–7.55%) were positive for vanA and none were positive for vanB. Routine screening of all patients at admission may be effective in hospital settings with high VRE prevalence, whereas the benefit of screening for VRE in hospitals with a low prevalence may be restricted to specific patient populations.

Enkirch, Theresa; Mernelius, Sara; Magnusson, Cecilia; Kühlmann‐Berenzon, Sharon; Bengnér, Malin; Åkerlund, Thomas; Rizzardi, Kristina

doi: 10.1111/apm.13270pmid: 35980252

Clostridioides difficile infections (CDIs) in Sweden are mostly hospital‐associated (HA) with limited knowledge regarding community‐associated (CA) infections. Here, we investigated the molecular epidemiology of clinical isolates of CA‐CDI and HA‐CDI in a Swedish county. Data and isolates (n = 156) of CDI patients (n = 122) from Jönköping county, October 2017–March 2018, were collected and classified as CA (without previous hospital care or onset ≤2 days after admission or >12 weeks after discharge from hospital) or HA (onset >3 days after hospital admission or within 4 weeks after discharge). Molecular characterization of isolates included PCR ribotyping (n = 156 isolates) and whole genome sequencing with single nucleotide polymorphisms (SNP) analysis (n = 53 isolates). We classified 47 patients (39%) as CA‐CDI and 75 (61%) as HA‐CDI. Between CA‐CDI and HA‐CDI patients, we observed no statistically significant differences regarding gender, age, 30‐day mortality or recurrence. Ribotype 005 (RR 3.1; 95% CI: 1.79–5.24) and 020 (RR 2.5; 95% CI: 1.31–4.63) were significantly associated with CA‐CDI. SNP analysis identified seven clusters (0–2 SNP difference) involving 17/53 isolates of both CA‐CDI and HA‐CDI. Molecular epidemiology differed between CA‐CDI and HA‐CDI and WGS analysis suggests transmission of CDI within and between hospitals and communities.

Mane, Arati; Jain, Shilpa; Jain, Ankita; Nema, Vijay; Kurle, Swarali; Saxena, Vandana; Pereira, Michael; Sirsat, Atul; Pathak, Gaurav; Bhoi, Vikalp; Bhavsar, Shailaja; Panda, Samiran

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Likońska, Aleksandra; Gawrysiak, Mateusz; Gajewski, Adrian; Klimczak, Kinga; Michlewska, Sylwia; Szewczyk, Robert; Gulbas, Izabela; Chałubiński, Maciej

doi: 10.1111/apm.13269pmid: 35959516

Vascular endothelium is a semi‐permeable barrier that regulates the flow of nutrients, ions, cytokines and immune cells between blood and tissues. Barrier properties of endothelium, its ability to regenerate and the potential for secretion of inflammatory mediators play a crucial role in maintaining local tissue homeostasis. The lung vascular endothelial cells were shown to be infected by human rhinovirus (HRV) and generate antiviral, inflammatory and cytopathic responses. The current study reveals that in the long‐time manner, the lung vascular endothelium may efficiently limit the HRV replication via the IFN‐dependent 2′‐5′‐oligoadenylate synthetase 1 activation. This leads to the restoration of integrity accompanied by the up‐regulation of adherens and tight junctions, increase of metabolic activity and proliferation rate. Secondly, HRV16‐infected cells show delayed and transient up‐regulation of the expression of vascular endothelial growth factor (VEGF), fibroblast growth factor, angiopoietin 1 and 2, and neuropilin‐1, as well as VEGF receptors. The lung vascular endothelium infected with HRV may limit the infection, recover in time, and regain barrier properties and metabolic functions, thus leading to the restoration of integrated barrier tissue.