A note on preconditioning weighted linear least squares, with consequences for weakly-constrained variational data assimilation

The effect of preconditioning linear weighted least-squares using an approximation of the model matrix is analyzed, showing the interplay of the eigenstructures of both the model and weighting matrices. A small example is given illustrating the resulting potential inefficiency of such preconditioners. Consequences of these results in the context of the weakly-constrained 4D-Var data assimilation problem are finally discussed.Comment: 10 pages, 2 figure

CD4(+)IL-13(+) cells in peripheral blood well correlates with the severity of atopic dermatitis in children

In atopic dermatitis (AD) a Th1/Th2 imbalance has been reported, and interleukin (IL)-13 seems to play a pivotal role in the inflammatory network. We tried to assess the correlation between the immunological marker CD4(+)IL-13(+) and the clinical phase of extrinsic AD in children

Evidence of greater severity of diabetic foot ulcers during COVID-19 pandemic: A real-life single-centre cohort study

Aims: In the Sars-Cov-2 pandemic era, patients with diabetes mellitus (DM) manifested more severe forms of Sars-Cov-2 with greater mortality than non-diabetic patients. Several studies documented more aggressive forms of diabetic foot ulcers (DFU) during the pandemic period even though the results were not unanimously confirmed. The aim of this study was to evaluate the clinical-demographic differences between a cohort of Sicilian diabetic patients hospitalised for DFU in the pre-pandemic 3 years and a cohort of patients hospitalised in the pandemic 2 years.Materials and Methods: One hundred and eleven patients from the pre-pandemic period 2017-2019 (Group A) and 86 patients from the pandemic period 2020-2021 (Group B) with DFU, admitted to the division of Endocrinology and Metabolism of the University Hospital of Palermo, were retrospectively evaluated. The clinical assessment of the type, staging and grading of the lesion, and the infective complication from DFU was performed.Results: No differences in HbA1c values were observed between the two groups. Group B showed a significantly higher prevalence of male subjects (p = 0.010), neuro-ischaemic ulcers (p < 0.001), deep ulcers with involvement of bones (p < 0.001), white blood count levels (p < 0.001), and reactive C protein (p = 0.001) compared to group A.Conclusions: Our data show that in the COVID-19 pandemic, a greater severity of ulcers requiring a significantly greater number of revascularisations and more expensive therapy, but without an increase in the amputation rate, was observed. These data provide novel information on the impact of the pandemic on diabetic foot ulcer risk and progression

Ultrasound Parameters Can Accurately Predict the Risk of Malignancy in Patients with "Indeterminate TIR3b" Cytology Nodules: A Prospective Study

The increase in the incidence of thyroid nodules with cytological findings of TIR3b requires the identification of predictive factors of malignancy. We prospectively evaluated 2160 patients from January 2018 to June 2022 and enrolled 103 patients with indeterminate cytology TIR3b nodules who underwent total (73 patients) and hemi-thyroidectomy (30 patients). Among them, 61 had a histological diagnosis of malignancy (30 classic papillary thyroid carcinoma, 19 had follicular papillary thyroid carcinoma variant, 3 had Hurtle cell carcinoma and 9 had follicular thyroid carcinoma), while 42 had a benign histology. Clinical, ultrasonographic and cytological characteristics were recorded. In addition, BRAF mutation was analysed. Patients with a histological diagnosis of malignancy had a higher frequency of nodule diameter <= 11 mm (p = 0.002), hypoechogenicity (p < 0.001), irregular borders (p < 0.001), peri- and intralesional vascular flows (p = 0.004) and microcalcifications (p = 0.001) compared to patients with benign histology. In contrast, patients with benign histology had more frequent nodules with a halo sign (p = 0.012) compared to patients with histological diagnosis of malignancy. No significant differences were found in BRAF mutation between the two groups. Our study suggests that the combination of ultrasonographic and cytological data could be more accurate and reliable than cytology alone in identifying those patients with TIR3b cytology and a histology of malignancy to be referred for thyroidectomy, thus reducing the number of patients undergoing thyroidectomy for benign thyroid disease

In Vitro Identification and Characterization of CD133pos Cancer Stem-Like Cells in Anaplastic Thyroid Carcinoma Cell Lines

Background: Recent publications suggest that neoplastic initiation and growth are dependent on a small subset of cells, termed cancer stem cells (CSCs). Anaplastic Thyroid Carcinoma (ATC) is a very aggressive solid tumor with poor prognosis, characterized by high dedifferentiation. The existence of CSCs might account for the heterogeneity of ATC lesions. CD133 has been identified as a stem cell marker for normal and cancerous tissues, although its biological function remains unknown. Methodology/Principal Findings: ATC cell lines ARO, KAT-4, KAT-18 and FRO were analyzed for CD133 expression. Flow cytometry showed CD133pos cells only in ARO and KAT-4 (6469% and 57612%, respectively). These data were confirmed by qRT-PCR and immunocytochemistry. ARO and KAT-4 were also positive for fetal marker oncofetal fibronectin and negative for thyrocyte-specific differentiating markers thyroglobulin, thyroperoxidase and sodium/iodide symporter. Sorted ARO/ CD133pos cells exhibited higher proliferation, self-renewal, colony-forming ability in comparison with ARO/CD133neg. Furthermore, ARO/CD133pos showed levels of thyroid transcription factor TTF-1 similar to the fetal thyroid cell line TAD-2, while the expression in ARO/CD133neg was negligible. The expression of the stem cell marker OCT-4 detected by RT-PCR and flow cytometry was markedly higher in ARO/CD133pos in comparison to ARO/CD133neg cells. The stem cell markers c- KIT and THY-1 were negative. Sensitivity to chemotherapy agents was investigated, showing remarkable resistance to chemotherapy-induced apoptosis in ARO/CD133pos when compared with ARO/CD133neg cells. Conclusions/Significance: We describe CD133pos cells in ATC cell lines. ARO/CD133pos cells exhibit stem cell-like features - such as high proliferation, self-renewal ability, expression of OCT-4 - and are characterized by higher resistance to chemotherapy. The simultaneous positivity for thyroid specific factor TTF-1 and onfFN suggest they might represent putative thyroid cancer stem-like cells. Our in vitro findings might provide new insights for novel therapeutic approaches

Pregnancy, gestational diabetes, thyroid function: our experience

This is a retrospective study of 112 patients with GDM. The purpose is to evaluate the relationship between GDM and impaired thyroid function. All the patients were evaluated: TSH, FT4 and glycosylated hemoglobin (HbA1c). The normal range for TSH is between 0,45 and 2,5 μU/ml; for FT4 is instead between 0,9 and 1,8 ng/dl; for HbA1c is less than 6%. Patients with elevated TSH and low levels of free thyroxine were diagnosed as "hypothyroid"; those with elevated TSH and FT4 in the standard as "subclinical hypothyroid"; pregnant women who had high TSH and low FT4 were diagnosed as "hyperthyroid"; women with low TSH and normal FT4 as "subclinical hyperthyroid". Patients who had normal levels of both thyrotropin and free thyroxine were considered "euthyroid". Based on the values of TSH and FT4 we obtained the following results: 77 patients (68.75%) euthyroid; 18 (16.1%) subclinical hypothyroidism; 12 (10.7%) hypothyroid; 5 patients (4.4%) subclinical hyperthyroidism. Our study confirms the association between thyroid disease and gestational diabetes. In addition, the hypothyroid patients insulin-treated, compared with euthyroid, increased the insulin requirement. The results show that women with GDM have a risk greater for both clinical and subclinical hypothyroidism; for this reason it is advisable to carry out a program of screening for thyroid function

Editorial: Recent Advances in Thyroid Surgery

Thyroid surgery has been, since its earliest application, one of the most notable fields in medicine, illustrated by the fact that the Nobel Prize in Medicine was won, for the first time, for thyroid surgery by Emil Theodor Kocher (1841–1917) in 1909, for his contributions to thyroid physiology, pathology, and surgery [...

Multimodal Surgical and Medical Treatment for Extensive Rhinocerebral Mucormycosis in an Elderly Diabetic Patient: A Case Report and Literature Review

Diabetes is a well-known risk factor for invasive mucormycosis with rhinocerebral involvement. Acute necrosis of the maxilla is seldom seen and extensive facial bone involvement is rare in patients with rhino-orbital-cerebral mucormycosis. An aggressive surgical approach combined with antifungal therapy is usually necessary. In this report, we describe the successful, personalized medical and surgical management of extensive periorbital mucormycosis in an elderly diabetic, HIV-negative woman. Mono- or combination therapy with liposomal amphotericin B (L-AmB) and posaconazole (PSO) and withheld debridement is discussed. The role of aesthetic plastic surgery to preserve the patient’s physical appearance is also reported. Any diabetic patient with sinonasal disease, regardless of their degree of metabolic control, is a candidate for prompt evaluation to rule out mucormycosis. Therapeutic and surgical strategies and adjunctive treatments are essential for successful disease management. These interventions may include combination therapy. Finally, a judicious multimodal treatment approach can improve appearance and optimize outcome in elderly patients

Effects of Intraoperative Nerve Monitoring Techniques on Voice and Swallowing Disorders after Uncomplicated Thyroidectomy: Preliminary Report of a Bi-Institutional Prospective Study

Background: Voice and swallowing problems are frequently associated with thyroidectomy. Intermittent nerve monitoring (i-IONM) seems to provide a positive effect in reducing its prevalence. The aim of this study was to test the hypothesis that continuous intraoperative nerve monitoring (c-IONM) may reduce the prevalence of these disorders even further than i-IONM. Methods: This 3-arm prospective bi-institutional study compared 179 consecutive patients that underwent thyroidectomy: 56 without IONM, 55 with i-IONM and 67 with c-IONM. Neck dissections and laryngeal nerve palsies were excluded. Two questionnaires (VHI-10 for voice disorders and EAT-10 for swallowing disorders; both validated for Italian language use) were administered before and 1 month after surgery. Statistical significance was analyzed by the chi-squared test. Results: After thyroidectomy, no statistically significant differences were found in the three groups concerning EAT-10. although these symptoms seemed to be influenced by gastro-esophageal reflux. VHI-10 worsened in the “no-IONM” group compared with both i-IONM (p p < 0.04). Conclusion: Both i- and c-IONM improve voice quality independently of laryngeal nerve integrity. Reduced dissection and particularly restrained manipulation could explain these results, being particularly favorable for c-IONM