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Background: Although older people in nursing homes have a larger susceptibility to infectious diseases, the extent to which infectious diseases contribute to their mortality is unknown. Therefore, we quantified the associations between seasonal infectious diseases and all-cause mortality in Dutch nursing homes., Methods: We analyzed time series (January 2009 to December 2021) of the weekly sentinel surveillance of infectious diseases in Dutch nursing homes. A generalized linear model with binomial distribution and identity link was used to associate the proportion of all-cause mortality with the incidence of infections: COVID-19 (2020-2021), gastroenteritis (GE), influenza-like illness (ILI), and lower respiratory tract infections (LRTIs) at 0- to 4-week time-lags (mortality incidence at 0 to 4 weeks after infections incidence)., Results: Over 13 years, 81 nursing homes participated, with 20 to 35 homes each year (mean: 26). A total of 11,555 all-cause deaths occurred over 1,864,667 resident weeks, averaging a mortality incidence of 6.2 per 1000 resident weeks. All 4 tested infectious diseases exhibited a significant association with all-cause mortality in nursing homes (P ≤ .01). Collectively, these infectious diseases were associated with 18.6% (95% CI, 17.8%-19.3%) of all deaths. The association between mortality and ILI was significant in 7 of 12 ILI seasons. Yearly mortality associated with the specific infectious diseases was as follows: LRTI (10.2%; 95% CI, 9.6%-10.8%), ILI (8.2%; 95% CI, 7.5%-8.9%) (over the 7 of 12 significant seasons), COVID-19 (6.5%; 95% CI, 5.4%-7.7%) (over 2019-2021 as there was no previous SARS-CoV-2 circulation), and GE (2.3%; 95% CI, 2.0%-2.5%)., Conclusion and Implications: In nursing homes, the occurrence of seasonal respiratory and gastrointestinal infections is associated with nearly one-fifth of all-cause deaths. Although infection prevention and surveillance may already be performed in some nursing homes, it is vital to implement, and enhance targeted strategies like (hand) hygiene protocols, environmental cleaning practices, reducing droplet and aerosol transmission, and vaccination to effectively address specific infections., Competing Interests: Disclosure H.v.W. declares financial and nonfinancial research support from DaVolterrra and bioMérieux; financial research support from LimmaTech; and consultancy fees from MSD and Sanofi-Pasteur. All payments to the University Medical Centre Utrecht. The other authors declare no conflict of interest., (Copyright © 2024 Post-Acute and Long-Term Care Medical Association. Published by Elsevier Inc. All rights reserved.)

Herein, we have disclosed a rare example of an intramolecular doubly vinylogous Michael addition (DVMA). The reaction design exploits the innate reactivity of ortho -heteroatom substituted para -quinone methide ( p -QM) derivatives. The sequential reaction of p -QMs and activated allyl halides proceeds through heteroatom-allylation, DVMA and oxidation to furnish a diverse range of 2-alkenyl benzofuran and 2-alkenyl indole derivatives in high yields.

Aims: Insertable cardiac monitors (ICMs) are indicated for long-term monitoring of unexplained syncope or palpitations, and for detection of bradycardia, ventricular tachycardia, and/or atrial fibrillation (AF). The aim of our study was to evaluate the safety and clinical value associated with a new generation ICM (Confirm Rx™, Abbott, Illinois, USA), featuring a new remote monitoring system based on smartphone patient applications., Methods and Results: The SMART Registry is an international prospective observational study. The main endpoints were ICM safety (incidence of serious adverse device and procedure-related events (SADEs) at 1 month), ICM clinical value (incidence of device-detected true arrhythmias and of clinical diagnoses and interventions), and patient-reported experience measurements (PREMs). A total of 1400 subjects were enrolled. ICM indications included syncope (49.1%), AF (18.8%), unexplained palpitations (13.6%), risk of ventricular arrhythmia (6.6%), and cryptogenic stroke (6.0%). Freedom from SADEs at 1 month was 99.4% (95% Confidence Interval: 98.8-99.7%). In the 6-month monitoring period, the ICM detected true cardiac arrhythmias in 45.7% of patients and led to clinical interventions in a relevant proportion of patients; in particular, a pacemaker implant was performed after bradycardia detection in 8.9% of subjects who received an ICM for syncope and oral anticoagulation therapy was indicated after AF detection in 15.7% of subjects with cryptogenic stroke. PREMs showed that 78.2% of subjects were satisfied with the remote monitoring patient app., Conclusion: The evaluated ICM is associated with an excellent safety profile and high diagnostic yield. Patients reported positive experiences associated with the use of their smartphone for the device remote monitoring., Competing Interests: Conflict of interest: W.L., A.G., and C.S.H. are employees of Abbott. All remaining authors have declared no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Purpose: Minimally invasive radical hysterectomy has been associated with increased recurrence of disease and worse survival compared with open radical hysterectomy for early-stage cervical cancer. We evaluated patterns of recurrence and histopathologic risk factors in patients who underwent robotic radical hysterectomy (RRH)., Methods: Patients who underwent RRH (4/2007-12/2018) were evaluated for specific locations of recurrent disease, disease-free survival, overall survival (OS), and histopathologic risk factors for recurrence. Inclusion criteria were follow-up ≥ 1 year, histology with adenocarcinoma, adenosquamous, or squamous carcinoma and clinical stage IA2 to IB ≤ 4-cm tumor size cervical cancers (FIGO-2018)., Results: A total of 140 patients underwent RRH and 112 met criteria. Median tumor size was 2.1 cm [interquartile range (IQR): 1.1-3.3]. Median follow-up was 61 months (IQR: 36-102). Fifty (45%) patients underwent adjuvant radiation ± cisplatin with either Sedlis' or Peters' risk factors. There were 11 (9.8%) recurrences with median disease-free survival of 12 (IQR 8.5) months. All patients with recurrence had measured tumor size ≥ 2 cm (median tumor size 3-cm (IQR: 2.6-4.0). Tumor size > 2 cm was associated with Sedlis' intermediate-risk factors (p < 0.05) and Peters' high-risk factors (p < 0.05). Forty patients underwent preoperative conization, and two (5%) with deep positive margins in lesions > 2 cm recurred. Five (4.5%) of patients had carcinomatosis representing 45% of all recurrences. Carcinomatosis was associated with reduced OS compared with other recurrence patterns (22 months vs. 7.8 years, p < 0.05)., Conclusions: Carcinomatosis was observed in early-stage cervical cancers treated with RRH and was associated with reduced OS. All recurrences were associated with lesions ≥ 2 cm, and no recurrences were identified with negative conization margins., (© 2021. Society of Surgical Oncology.)

Intravenous leiomyomatosis (IVL) is an uncommon variant of leiomyoma characterized by intravascular proliferation of a histologically benign smooth muscle tumor extending beyond the uterus into the distant great vessels. Leiomyomatosis may reach the inferior vena cava, right atrium, and pulmonary arteries. Owing to its rare occurrence, intracardiac leiomyomatosis has been reported as isolated case reports and small case series. Early diagnosis and prompt surgical intervention are vital to prevent cardiac symptoms, pulmonary embolism, and sudden death. Complete tumor resection is essential for a favorable outcome, usually assisted with multimodal surgical imaging and multidisciplinary surgical planning. Herein, we report the case of a 50-year-old female that presented with a three-month history of abdominal pain and lower extremity edema with evidence of IVL extending to the inferior vena cava and right atrium. The patient was managed with a single-stage surgery involving cardiopulmonary bypass and excision of the right atrial and inferior vena cava tumors, as well as modified radical total abdominal hysterectomy and bilateral salpingo-oophorectomy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Objective: Our objective was to assess safety and adverse events associated with intraperitoneal Olvi-Vec virotherapy in patients with platinum-resistant or refractory ovarian cancer (PRROC). Secondary objectives included objective response rate (ORR) per RECIST 1.1 and progression-free survival (PFS)., Methods: Olvi-Vec is a modified vaccinia virus that causes oncolysis and immune activation. An open-label phase 1b trial using a 3 + 3 dose escalation was conducted. Intraperitoneal Olvi-Vec was given as monotherapy in two consecutive daily doses. Translational analyses included anti-virus antibody levels, viral shedding, circulating tumor cells (CTCs) and T cells., Results: Twelve patients (median age: 69 years, range: 45-77) with median 5 prior therapies (range: 2-10) and 2 prior platinum lines (range: 1-5) were enrolled. There were three dose level cohorts: 3 × 10 9 (n = 6), 1 × 10 10 (n = 5), and 2.5 × 10 10 (n = 1) plaque forming units (PFU)/day on two consecutive days. Treatment-related adverse events (TRAEs) included G1/G2 nausea (n = 6), fever (n = 6), abdominal distention (n = 5), and abdominal pain (n = 4). There were no Grade 4 TRAEs, no dose relationship to TRAEs, and no deaths attributed to Olvi-Vec. The ORR was 9% (1/11). Stable disease (SD) was 64% (7/11), and SD ≥15 weeks was 46% (5/11). Median PFS was 15.7 weeks (95%CI: 5.7-34.5), including extended PFS in four patients (23.2, 34.5, 59.4+ and 70.8 weeks). Three patients had extended overall survival (deceased 33.6 months, and alive with disease at 54 and 59 months). CTCs diminished in 6/8 (75%) baseline-positive patients. Immune activation was demonstrated from virus-enhanced tumor infiltration of CD8+ T-cells and activation of tumor-specific T-cells in peripheral blood., Conclusions: Oncolytic viral therapy with intraperitoneal Olvi-Vec showed promising safety, clinical activities, and immune activation in patients with PRROC, warranting further clinical investigation., Competing Interests: Declaration of Competing Interest Dr. Robert W. Holloway serves as Chair, Clinical Advisory Board on Gynecologic Cancers to Genelux. None of the other authors have any potential financial or commercial conflict of interest associated with this research manuscript., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Consensus molecular subtyping (CMS) of colorectal cancer has potential to reshape the colorectal cancer landscape. We developed and validated an assay that is applicable on formalin-fixed, paraffin-embedded (FFPE) samples of colorectal cancer and implemented the assay in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory., Experimental Design: We performed an in silico experiment to build an optimal CMS classifier using a training set of 1,329 samples from 12 studies and validation set of 1,329 samples from 14 studies. We constructed an assay on the basis of NanoString CodeSets for the top 472 genes, and performed analyses on paired flash-frozen (FF)/FFPE samples from 175 colorectal cancers to adapt the classifier to FFPE samples using a subset of genes found to be concordant between FF and FFPE, tested the classifier's reproducibility and repeatability, and validated in a CLIA-certified laboratory. We assessed prognostic significance of CMS in 345 patients pooled across three clinical trials., Results: The best classifier was weighted support vector machine with high accuracy across platforms and gene lists (>0.95), and the 472-gene model outperforming existing classifiers. We constructed subsets of 99 and 200 genes with high FF/FFPE concordance, and adapted FFPE-based classifier that had strong classification accuracy (>80%) relative to "gold standard" CMS. The classifier was reproducible to sample type and RNA quality, and demonstrated poor prognosis for CMS1-3 and good prognosis for CMS2 in metastatic colorectal cancer ( P < 0.001)., Conclusions: We developed and validated a colorectal cancer CMS assay that is ready for use in clinical trials, to assess prognosis in standard-of-care settings and explore as predictor of therapy response., (©2020 American Association for Cancer Research.)

Purpose: To establish the bilateral pelvic concordance rate of the sentinel lymph node (SLN) and determine the likelihood of lymph node metastasis in cases of mapping failure., Methods: A database analysis was performed on 414 patients with clinical stage I endometrial cancer who underwent SLN mapping followed by robotic hysterectomy and completion pelvic (n=414, 100%) and aortic (n=186, 44.9%) lymphadenectomy from March 2011 to August 2016. Stage, histology, SLN sites, and surgico-pathologic findings were analyzed. The bilateral concordance rate of SLN location, successful unilateral and bilateral mapping rates, false negative rate, and non-SLN metastasis associated with mapping failure were calculated., Results: Histologies included 354 (85.5%) endometrioid, 39 (9.4%) serous, 16 (3.9%) carcinosarcoma, 4 (1.0%) clear cell, and 1 (0.2%) undifferentiated. Final stages included 262 (63.3%) IA, 36 (8.7%) IB, 15 (3.6%) II, 6 (1.4%) IIIA, 68 (16.4%) IIIC1, and 27 (6.5%) IIIC2. Bilateral SLN mapping was successful in 355 (85.7%) patients, and 266 (74.9%) demonstrated mapping to the symmetrical lymphatic group contralaterally. The mapping failure rate was 13.5% (56/414) unilaterally and 0.7% (3/414) bilaterally. SLN locations were external iliac (69.1%), obturator (25.1%), internal iliac (2.2%), common iliac (1.9%), pre-sacral (0.9%), aortic (0.4%), parametrial (0.3%), and para-rectal (0.1%). Lymph node metastases were identified in 95 (22.9%) pelvic and 27 (6.5%) aortic nodes. 10 (16.9%) cases with mapping failure had lymph node metastasis on completion lymphadenectomy, similar to the proportion of SLNs with metastases (p=0.35). However, macro-metastases were more common in mapping failure completion lymphadenectomies than in the positive SLNs (80% vs 22.3%, p<0.001)., Conclusion: The contralateral SLN location concordance rate was 75%. Most SLNs were along the medial external iliac or obturator locations. The rate of positive lymph nodes associated with SLN mapping failure was 16.9%, similar to the overall node-positive rate. The detection of pelvic node metastasis with SLN mapping failure was largely populated with macro-metastases and confirms the necessity of completion lymphadenectomy with mapping failure., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

A unique intramolecular vinylogous Michael addition leading to the synthesis of heterocycles has been disclosed. Base-promoted one-pot sequential O-allylation of o-hydroxy-cinnamates or -cinnamonitrile or -chalcones with γ-bromocrotonates followed by an intramolecular conjugate addition of vinylogous Michael donors resulted in the formation of highly substituted benzofuran derivatives in good to excellent yields. The intramolecular event followed by two [1,3]-H shifts leading to aromatization appears to be the key to the success of this unprecedented transformation.

Aim: In the present investigation, oral dissolving/dispersible/disintegrating tablets (ODTs) of clopidogrel were designed with a view to enhance the bioavailability and patient compliance by two different methods, namely, direct compression and effervescent methods using directly compressible excipient and treated agar (TAG)., Materials & Methods: In the direct compression method, TAG was used as a disintegrant and another method used a mixture of sodium bicarbonate and tartaric acid along with TAG as disintegrants., Results: Among the directly compressed tablets, treated agar formulation 3 and among the effervescent tablets, treated agar and effervescent formulation 4 was found to be promising., Conclusion: Treated agar formulation 3 prepared by direct compression method emerged as an overall best formulation based on the in vitro drug release characteristics.

A novel organocatalytic approach, harnessing the unique reactivities of N-heterocyclic carbenes (NHCs), has been revealed for the construction of indoles. The NHC-catalysed atom economical synthesis of a wide range of 2-substituted indole-3-acetic acid derivatives is displayed. Strategic application of the developed method was demonstrated for a short synthesis of a cyclin-dependent kinase (CDK) inhibitor: paullone.

The extracellular matrix is a complex integrated system responsible for the physiologic properties of connective tissue. Collagen is the major extracellular component that is altered in pathologic conditions, mainly periodontitis. The destruction involves proteolytic enzymes, primarily matrix metalloproteinases (MMPs), which play a key role in mediating and regulating the connective tissue destruction in periodontitis. The study group included 40 patients with clinically diagnosed chronic periodontitis. The control group included 20 patients with clinically normal gingiva covering impacted third molars undergoing extraction or in areas where crown-lengthening procedures were performed. MMP-13 expression was demonstrated using immunohistochemistry in all the gingival biopsies, and the data were analyzed statistically. MMP-13 expression was observed more in chronic periodontitis when compared with normal gingiva. MMP-13 expression was expressed by fibroblasts, lymphocytes, macrophages, plasma cells, and basal cells of the sulcular epithelium. Comparative evaluation of all the clinical and histologic parameters with MMP-13 expression showed high statistical significance with Spearman correlation coefficient. Elevated levels of MMP-13 may play a role in the pathogenesis of chronic periodontitis. There is a direct correlation of increased expression of MMP-13 with various clinical and histologic parameters in disease severity.

Desmoplastic fibroma is a rare benign and locally aggressive myo fibroblastic tumour, frequently seen in the second or third decades of life. The mandible and the maxilla are infrequently involved, and the mandible is the most commonly affected of the facial bones. Nevertheless, reports of desmoplastic fibroma affecting the mandible are scarce in the literature. This article reports a rare case of desmoplastic fibroma affecting the angle of the mandible in a 10-year-old Indian male. In addition, a review of literature relating to desmoplastic fibroma affecting the angle of the mandible is presented.

Fibroblasts are a major stromal cell type present in human connective tissue maintaining the structural integrity in health. Depending on the situation, location and various conditions, fibroblasts exhibit considerable variation in morphology, size and shape that suggest the existence of discrete cellular subsets. The purpose of this short communication is to provide information regarding the heterogenecity of fibroblasts and its variability in physiological and pathological conditions.

Protein-ligand interactions were studied for bovine insulin-amino sugar systems under electrospray ionisation mass spectrometry conditions. The isomeric amino sugars showed differences in the relative abundance of 1:1 protein-ligand complex formation. The electrospray ionisation and tandem mass spectrometry results of the complex clearly demonstrated that the differences in the interaction of isomeric sugars with insulin are mainly due to the differences in their gas-phase basicity. The same phenomenon is replicated in the formation of complexes between insulin and other ligands, such as amino acids, as well as in the binding of the amino sugars with amyloid β 1-40 peptide.

Oral lichen planus is a cell-mediated immune condition and is infrequently encountered in children, with a prevalence of about 0.03 percent in childhood. Reports of oral lichen planus affecting children are scarce in the literature. The purpose of this article is to present a rare case of oral lichen planus affecting a seven-year-old child without concomitant cutaneous lesions. Intraoral lesions and associated mild discomfort treated with topical corticosteroid therapy and a plaque control regime resulted in a favorable result.