Occurrence of the Omicron variant of SARS-CoV-2 in northern Viet Nam in early 2022.

The Omicron variant caused a surge of infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Viet Nam in early 2022, signalling community transmission. We report on active whole-genome sequencing surveillance of positive SARS-CoV-2 samples collected at that time in northern Viet Nam from international arrivals and community clusters. We used an amplicon protocol developed with 14 polymerase chain reaction products and the Illumina iSeq 100 platform. Overall, 213 nasopharyngeal or throat swabs were analysed, of which 172 samples were identified with the Omicron variant. Of these, 80 samples were collected from community cases in February 2022, among which 59 samples were sublineage BA.2 and one sample was the recombinant XE variant. Our results indicated that Omicron had replaced Delta as the dominant variant in a very short period of time and that continuously conducting active whole-genome sequencing surveillance is necessary in monitoring the evolution and genomic diversity of SARS-CoV-2 in Viet Nam.

Accuracy and precision of zero-heat-flux temperature measurements with the 3M™ Bair Hugger™ Temperature Monitoring System: a systematic review and meta-analysis.

Zero-heat-flux thermometers provide clinicians with the ability to continuously and non-invasively monitor body temperature. These devices are increasingly being used to substitute for more invasive core temperature measurements during surgery and in critical care. The aim of this review was to determine the accuracy and precision of zero-heat-flux temperature measurements from the 3M™ Bair Hugger™ Temperature Monitoring System. Medline and EMBASE were searched for studies that reported on a measurement of core or peripheral temperature that coincided with a measurement from the zero-heat-flux device. Study selection and quality assessment was performed independently using the Revised Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2). The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach was used to summarize the strength of the evidence. Pooled estimates of the mean bias and limits of agreement with outer 95% confidence intervals (population limits of agreement) were calculated. Sixteen studies were included. The primary meta-analysis of zero-heat-flux versus core temperature consisted of 22 comparisons from 16 individual studies. Data from 952 participants with 314,137 paired measurements were included. The pooled estimate for the mean bias was 0.03 °C. Population limits of agreement, which take into consideration the between-study heterogeneity and sampling error, were wide, spanning from - 0.93 to 0.98 °C. The GRADE evidence quality rating was downgraded to moderate due to concerns about study limitations. Population limits of agreement for the sensitivity analysis restricted to studies rated as having low risk of bias across all the domains of the QUADAS-2 were similar to the primary analysis. The range of uncertainty in the accuracy of a thermometer should be taken into account when using this device to inform clinical decision-making. Clinicians should therefore consider the potential that a temperature measurement from a 3M™ Bair Hugger™ Temperature Monitoring System could be as much as 1 °C higher or lower than core temperature. Use of this device may not be appropriate in situations where a difference in temperature of less than 1 °C is important to detect.

Virus detections among patients with severe acute respiratory illness, Northern Vietnam.

Severe acute respiratory illness (SARI) is a major cause of death and morbidity in low- and middle-income countries, however, the etiologic agents are often undetermined due to the lack of molecular diagnostics in hospitals and clinics. To examine evidence for select viral infections among patients with SARI in northern Vietnam, we studied 348 nasopharyngeal samples from military and civilian patients admitted to 4 hospitals in the greater Hanoi area from 2017-2019. Initial screening for human respiratory viral pathogens was performed in Hanoi, Vietnam at the National Institute of Hygiene and Epidemiology (NIHE) or the Military Institute of Preventative Medicine (MIPM), and an aliquot was shipped to Duke-NUS Medical School in Singapore for validation. Patient demographics were recorded and used to epidemiologically describe the infections. Among military and civilian cases of SARI, 184 (52.9%) tested positive for one or more respiratory viruses. Influenza A virus was the most prevalent virus detected (64.7%), followed by influenza B virus (29.3%), enterovirus (3.8%), adenovirus (1.1%), and coronavirus (1.1%). Risk factor analyses demonstrated an increased risk of influenza A virus detection among military hospital patients (adjusted OR, 2.0; 95% CI, 1.2-3.2), and an increased risk of influenza B virus detection among patients enrolled in year 2017 (adjusted OR, 7.9; 95% CI, 2.7-22.9). As influenza A and B viruses were commonly associated with SARI and are treatable, SARI patients entering these hospitals would benefit if the hospitals were able to adapt onsite molecular diagnostics.

Duodenal Xanthoma: From Specks to Obstruction.

Xanthomas within the gastrointestinal tract occur secondary to a mucosal insult. When enough cells accumulate, their appearance can range from small nodules studding the intestinal mucosa to bandlike infiltrations to pseudotumor-like masses within the intestine with fibrosis and inflammation resembling malignancy. When large enough, they can produce symptoms of obstruction such as vomiting, abdominal pain, distention, and dysmotility. This case demonstrates the epidemiology, clinical presentation, diagnosis, and treatment of duodenal xanthomas.

Injection site pseudosarcoma in piriformis syndrome.

AIMS: Pseudosarcomatous reactive myofibroblastic proliferations have been described following surgery or trauma at a variety of anatomical sites. These types of reactions have not been previously described at injection sites. Here we evaluated prevalence, morphologic patterns and clinical resolution of such lesions. METHODS AND RESULTS: We analyzed 266 surgical resection specimens obtained during the definitive treatment of piriformis syndrome. Three cases showed exuberant reactive fibroblastic/myofibroblastic intramuscular proliferations, mimicking a sarcoma. In all three cases the surgeries were found to be preceded by local injections of cortisone and bupivacaine. Clinical follow-up revealed no uncontrolled growth. CONCLUSIONS: As the clinical history of injections is often not provided, it is important to be aware of this pitfall when reviewing skeletal muscle resections for entrapment syndromes.

Monoclonal antibodies targeting IL-1 beta reduce biomarkers of atherosclerosis in vitro and inhibit atherosclerotic plaque formation in Apolipoprotein E-deficient mice.

OBJECTIVE: Atherosclerosis is a condition that is increasingly contributing to worldwide mortality through complications such as stroke and myocardial infarction. IL-1ß plays multiple direct, local roles in the formation and stability of the atheroma by eliciting the production of additional cytokines and proteolytic enzymes from macrophages, endothelial cells (EC) and smooth muscle cells (SMC). We therefore tested whether an anti-IL-1ß antibody, XOMA 052, might inhibit the secretion of pro-atherogenic cytokines from macrophages in vitro and affect a positive outcome in the Apolipoprotein E-deficient mouse (ApoE(-/-)) model of atherosclerosis in vivo. METHODS AND RESULTS: In an in vitro co-culture model, XOMA 052 inhibited macrophage-induced secretion of key atherogenic cytokines from EC and SMC, including IL-6, IL-8, MCP-1 and TNFα. The release of degradative enzymes, such as the matrix metalloproteinases MMP-3 and MMP-9, was also decreased by XOMA 052. In addition, XOMA 052 inhibited the secretion of IL-7 from EC and IL-4 from SMC, cytokines not previously reported to be driven by IL-1ß in this context. In vivo, XMA052 MG1K, a chimeric murine version of XOMA 052, inhibited the formation of atherosclerotic lesions in the ApoE(-/-) model at all three doses tested. This effect was comparable to that reported for complete genetic ablation of IL-1ß or IL-1R1 on an ApoE(-/-) background and was associated with decreases in plasma non-HDL/HDL cholesterol ratio and plaque lipid content and macrophage infiltration. CONCLUSIONS: These results demonstrate for the first time that an antibody targeting IL-1ß can inhibit the progression of atherosclerosis in vivo, highlighting the importance of this key cytokine in cardiovascular disease.

Lack of HER2 overexpression and amplification in small intestinal adenocarcinoma.

HER2 overexpression and amplification have been studied as a therapeutic and prognostic target in a number of human cancers, including esophageal, gastric, and colorectal adenocarcinomas. However, HER2 status has not been well investigated in primary small intestinal adenocarcinoma, probably because of its rarity. In this study, we conducted immunohistochemical analysis and fluorescence in situ hybridization (FISH) for HER2 on 49 primary nonampullar small intestinal adenocarcinomas. The results showed a complete lack of HER2 protein expression in 47 cases (96%) by immunohistochemical analysis. Only 2 cases (4%) showed a 1+ staining pattern. No tumors exhibited 2+ or 3+ HER2 immunoreactivity. By FISH, none of the tumors, including those with 1+ HER2 immunoreactivity, exhibited HER2 gene amplification. These observations demonstrate that HER2 protein overexpression and gene amplification are infrequent events, if they occur at all, in small intestinal adenocarcinoma. Thus, routine immunohistochemical and/or FISH testing for HER2 for potential targeted anti-HER2 therapy may not be beneficial for patients with primary small intestinal adenocarcinoma.

The utility of PAX-2 and renal cell carcinoma marker immunohistochemistry in distinguishing papillary renal cell carcinoma from nonrenal cell neoplasms with papillary features.

PAX-2, a homeogene expressed during kidney development, has been studied as a marker of renal origin in both primary and metastatic clear cell renal cell carcinoma (RCC), but not in papillary neoplasms or in comparison with RCC marker (RCCma). We studied immunohistochemical expression of PAX-2 and RCCma in 24 papillary RCC (PRCC) and 66 nonrenal cell papillary neoplasms (NRCPN) from a variety of organs. Of the PRCC, 16/24 (67%) were positive for PAX-2; 23/24 (96%) were positive for RCCma. Of the NRCPN, 9/66 (14%) is positive for PAX-2 [4/10 (40%) ovarian papillary serous carcinomas, 5/9 (56%) uterine papillary serous carcinomas]; RCCma was positive in 28/66 (42%), including 9/9 (100%) papillary thyroid carcinomas, 8/10 (80%) ovarian papillary serous carcinomas, 4/9 (44%) uterine papillary serous carcinomas, 1/10 (10%) papillary urothelial carcinomas, 1/2 (50%) intraductal papillary mucinous carcinomas of the pancreas, 3/3 (100%) choroid plexus papillomas, 1/1 (100%) pituitary adenoma with papillary features, and 1/2 (50%) lung adenocarcinomas with papillary features. The sensitivity of PAX-2+/RCCma+ immunophenotype for PRCC was 58% with a specificity of 54%. There is significant overlap between the expressions of these markers in PRCC and NRCPN; however, the positivity of RCCma and/or PAX-2 is 100% sensitive for PRCC and may prove useful in the initial work up of metastases of unknown primary. PAX-2 and RCCma immunohistochemistry should be interpreted with caution in papillary neoplasms, with particular attention to the possibility of ovarian and uterine papillary serous carcinomas, which can express both PAX-2 and RCCma.

The utility of PAX-2 in distinguishing metastatic clear cell renal cell carcinoma from its morphologic mimics: an immunohistochemical study with comparison to renal cell carcinoma marker.

PAX-2 is a homeogene expressed during kidney development. Although immunohistochemical expression of PAX-2 has been described in a variety of primary renal cell carcinoma (RCC) subtypes and in metastatic RCC, its specificity as a marker of renal lineage in a metastatic setting has not been fully evaluated. In addition, its utility has not been directly compared with the most widely used antibody in this setting, renal cell carcinoma marker (RCCma). We studied PAX-2 expression in metastatic clear cell renal cell carcinoma (CC-RCC) and in a variety of nonrenal neoplasms with clear cytoplasm that may potentially mimic CC-RCC. Archival material from 27 CC-RCCs metastatic to various organs and 50 close morphologic mimics of CC-RCC were retrieved. Immunohistochemistry with PAX-2 and RCCmapi antibodies was performed on each case. Nuclear staining (PAX-2) or membranous staining (RCCma) was scored semiquantitatively. Twenty-three of 27 (85%) metastatic CC-RCCs showed nuclear immunoreactivity for PAX-2, whereas RCCma reactivity was found in 19 of 27 (70%). The immunoprofiles of the metastatic CC-RCC were PAX-2+/RCCma+: 19 of 27 (70%), PAX-2+/RCCma-: 5 of 27 (19%), PAX-2-/RCCma+: 2 of 27 (7%), and PAX-2-/RCCma-: 1 of 27 (4%). Five of the 50 mimics of CC-RCC (10%) had at least focal nuclear reactivity with PAX-2, including 1 of 3 parathyroid carcinomas (33%), 3 of 7 clear cell carcinomas of the ovary (43%), and the 1 clear cell papillary cystadenoma of the epididymis. Membranous RCCma reactivity was identified in 26 of the 50 mimics (52%). We conclude that PAX-2 is a useful marker for distinguishing metastatic CC-RCC from its potential morphologic mimics, but caution must be used in certain differential diagnostic settings where nonrenal tumors such as parathyroid carcinoma, ovarian clear cell carcinoma, and clear cell papillary cystadenoma of the epididymis were shown to express both PAX-2 and RCCma.

Androgens regulate the sexually dimorphic production of co-contained galanin and cholecystokinin in lumbar laminae VII and X neurons.

A population of rat lumbar laminae VII and X putative spinothalamic (STT) neurons that co-contain cholecystokinin-8 (CCK) and galanin (GAL) are sexually dimorphic. Males have a significantly greater number of these neurons, as well as having greater optical densities for both neuropeptides than females. Optical densities for GAL and CCK immunoreactivities in these lumbar neurons in rats that have the testicular feminization mutation (Tfm) are not significantly different from females; however, the number of these lumbar neurons in Tfm rats is significantly smaller than in females. These data suggest that androgens, as well as functional androgen receptors (that Tfm rats lack), are necessary for the establishment of these sexual dimorphisms. Functionally, these CCK- and GAL-containing neurons in the deep lumbar laminae may contribute to the establishment of known sex differences in the affective component of somatic and visceral nociception, as well as the sexually dimorphic nature of some pelvic diseases, e.g., irritable bowel syndrome or cystitis.

The translational regulation of lipoprotein lipase by epinephrine involves an RNA binding complex including the catalytic subunit of protein kinase A.

The balance of lipid flux in adipocytes is controlled by the opposing actions of lipolysis and lipogenesis, which are controlled primarily by hormone-sensitive lipase and lipoprotein lipase (LPL), respectively. Catecholamines stimulate adipocyte lipolysis through reversible phosphorylation of hormone-sensitive lipase, and simultaneously inhibit LPL activity. However, LPL regulation is complex and previous studies have described translational regulation of LPL in response to catecholamines because of an RNA-binding protein that interacts with the 3'-untranslated region of LPL mRNA. In this study, we identified several protein components of an LPL RNA binding complex. Using an LPL RNA affinity column, we identified two of the RNA-binding proteins as the catalytic (C) subunit of cAMP-dependent protein kinase (PKA), and A kinase anchoring protein (AKAP) 121/149, one of the PKA anchoring proteins, which has known RNA binding activity. To determine whether the C subunit was involved in LPL translation inhibition, the C subunit was depleted from the cytoplasmic extract of epinephrine-stimulated adipocytes by immunoprecipitation. This resulted in the loss of LPL translation inhibition activity of the extract, along with decreased RNA binding activity in a gel shift assay. To demonstrate the importance of the AKAPs, inhibition of PKA-AKAP binding with a peptide competitor (HT31) prevented epinephrine-mediated inhibition of LPL translation. C subunit kinase activity was necessary for LPL RNA binding and translation inhibition, suggesting that the phosphorylation of AKAP121/149 or other proteins was an important part of RNA binding complex formation. The hormonal activation of PKA results in the reversible phosphorylation of hormone-sensitive lipase, which is the primary mediator of adipocyte lipolysis. These studies demonstrate a dual role for PKA to simultaneously inhibit LPL-mediated lipogenesis through inhibition of LPL translation.