1-Hour OGTT Plasma Glucose as a Marker of Progressive Deterioration of Insulin Secretion and Action in Pregnant Women

Considering old GDM diagnostic criteria, alterations in insulin secretion and action are present in women with GDM as well as in women with one abnormal value (OAV) during OGTT. Our aim is to assess if changes in insulin action and secretion during pregnancy are related to 1-hour plasma glucose concentration during OGTT. We evaluated 3 h/100 g OGTT in 4,053 pregnant women, dividing our population on the basis of 20 mg/dL increment of plasma glucose concentration at 1 h OGTT generating 5 groups (<120 mg/dL, n = 661; 120–139 mg/dL, n = 710; 140–159 mg/dL, n = 912; 160–179 mg/dL, n = 885; and ≥180 mg/dL, n = 996). We calculated incremental area under glucose (AUCgluc) and insulin curves (AUCins), indexes of insulin secretion (HOMA-B), and insulin sensitivity (HOMA-R), AUCins/AUCgluc. AUCgluc and AUCins progressively increased according to 1-hour plasma glucose concentrations (both P < 0.0001 for trend). HOMA-B progressively declined (P < 0.001), and HOMA-R progressively increased across the five groups. AUCins/AUCgluc decreased in a linear manner across the 5 groups (P < 0.001). Analysing the groups with 1-hour value <180 mg/dL, defects in insulin secretion (HOMA-B: −29.7%) and sensitivity (HOMA-R: +15%) indexes were still apparent (all P < 0.001). Progressive increase in 1-hour OGTT is associated with deterioration of glucose tolerance and alterations in indexes of insulin action and secretion

Lumbar Endoscopic Microdiscectomy: Where Are We Now? An Updated Literature Review Focused on Clinical Outcome, Complications, and Rate of Recurrence

Endoscopic disc surgery (EDS) for lumbar spine disc herniation is a well-known but developing field, which is increasingly spreading in the last few years. Rate of recurrence/residual, complications, and outcomes, in comparison with standard microdiscectomy (MD), is still debated and need further data. We performed an extensive review based on the last 6 years of surgical series, systematic reviews, and meta-analyses reported in international, English-written literature. Articles regarding patients treated through endoscopic transforaminal or interlaminar approaches for microdiscectomy (MD) were included in the present review. Papers focused on endoscopic surgery for other spinal diseases were not included. From July 2009 to July 2015, we identified 51 surgical series, 5 systematic reviews, and one meta-analysis reported. In lumbar EDS, rate of complications, length of hospital staying, return to daily activities, and overall patients’ satisfaction seem comparable to standard MD. Rate of recurrence/residual seems higher in EDS, although data are nonhomogeneous among different series. Surgical indication and experience of the performing surgeon are crucial factors affecting the outcome. There is growing but still weak evidence that lumbar EDS is a valid and safe alternative to standard open microdiscectomy. Statistically reliable data obtained from randomized controlled trials (better if multicentric) are desirable to further confirm these results.</jats:p

The role of ankle plantar flexion in the monitoring of diabetic patients at risk of foot ulcer

Limited ankle joint mobility (AJM) is a major risk factor for ulcers and a useful parameter for monitoring the health of patients with diabetes. The aim of this study was to test the feasibility and usefulness of evaluating AJM for monitoring ulcerative risk. AJM in plantar (PF) and dorsiflexion (DF) was evaluated in 99 patients with diabetes, type1/type2: 50/49, (58/41;M/F), and 59 healthy controls (32:27/M:F). Patients and controls were divided into 6 groups by age and neuropathy: 32 young patients (group YD), mean age 12.4±2.0 yr, 29 young controls (group YC), mean age 11.4 ± 3.3 yr, 38 elderly patients without neuropathy (group ED), mean age 58.5 ±10.3 yr, 15 neuropathic patients without history of foot ulcer (group ND), mean age 62.1 ± 7.9 yr, 14 neuropathic patients with history of foot ulcer (group NUD), mean age 64 ± 8.4 yrs, and 30 elderly healthy controls (group EC), mean age 60.3 ± 6.4 yr. AJM was evaluated by an inclinometer with the patient lying supine, the subtalar joint in neutral position and with the ankle in the position freely taken at the beginning. The knee, corresponding to the evaluated ankle, was extended and put over a rigid 5-cm high support. Diabetes duration was respectively: group YD 5.5 ± 3.5 yr, ED 16.5 ± 10.6 yr; ND 18.2 ± 13.1 yr and NUD 13.7 ± 9.6 yr. The NUD group showed a more significant AJM reduction in DF and PF than all other groups (p < 0.005). The reduction was 40.1% compared to the EC group and 46.9% compared to the YC group (78.1 ± 18.4 vs 147.2 ± 19.1, 130.4 ± 15.1). Only the DF was significantly reduced in the NUD group compared to the ED group (p < 0.001). The YD had more reduced AJM in both movements compared to the young controls (YC) (p < 0.001) with PF more reduced than DF (30.9% vs 15.5%). Among patients and controls the elderly groups had significant reduction of only DF (EC vs YC p < 0.001; ED vs YD p < 0.05). As in previous studies, these results confirm that an AJM reduction of about 40% (28-32) in patients with diabetic neuropathy can be considered as a threshold for ulcer risk. The method used permits direct evaluation of AJM in plantar flexion that seems to show an early reduction in diabetic subjects, thereby providing useful information for patient monitoring

Diabetes, ankle joint mobility, aging, and foot ulcer

In diabetic patients the evaluation of how ankle joint mobility (AJM) can be useful in the identification of connective tissue alteration and risk of foot ulcer (FU). Plantar and dorsal flexion of foot were evaluated using an inclinometer in 87 patients (54 type 2 and 33 type 1), and 35 healthy sex- and age-matched control subjects. Patients with diabetes were followed up for diagnosis of FU over the next 8 years and subsequently, patients were subdivided into: those without a history of FU (18 type 1 and 33 type 2), those who had a history of FU detected before baseline evaluation (14 type 2) and those who had history of first ulceration detected by the 8th year of the evaluation period (7 type 2). Aging and diabetes caused a significant reduction in mobility of each of the movements investigated (p &lt; 0.001), whereas after adjusting for the confounding effect of age, diabetes specifically reduced plantar flexion (p &lt; 0.0001). AJM was significantly lower in those with history of previous FU compared to all the other groups (p &lt; 0.001). The first ulceration was detected in the same foot presenting lower AJM in 17 of the 22 subjects with diabetes with history of ulcer (77.27%). Diabetes and aging reduce AJM although diabetes seems to reduce plantar flexion to a more specific extent. Reduced AJM is mostly associated with a previous history of FU. The evaluation of AJM is a valid and reliable ulcer risk scale that indicates which foot is at higher ulcer risk

Musculoskeletal manifestations of diabetes mellitus: the role of exercise therapy in the treatment of limited joint mobility, muscle weakness and reduced gait speed

It is well known that limited joint mobility of the ankle and foot, impaired muscular performance and reduced gait speed are risk factors for ulceration in diabetic foot. The aim of this study was to evaluate the effect of an experimental protocol of exercise therapy on joint mobility, muscular strength and gait speed in a group of longterm diabetic subjects. The protocol consisted of a 12-week supervised training program; both joint mobility and muscular strength at the ankle were measured before and after exercise therapy by an inclinometer and isometric dynamometers respectively, in 26 diabetic subjects and compared to 17 healthy controls. Ankle joint mobility in plantar flexion was reduced about 36% and dorsal flexion by about 23% in diabetic subjects compared to controls (p&lt;0.001), but significantly increased after exercise therapy (p&lt;0.001 for both). Ankle muscular strength in plantar flexion was reduced by about 51% and in dorsal flexion by 30% in diabetic patients compared to controls, but these also significantly increased after exercise therapy (p&lt;0.001). Consequently, patients’ walking speed increased after exercise therapy by 0.28 m/s (p&lt;0.001). A 12-week supervised program of exercise therapy significantly improves joint mobility, muscular performance and walking speed in diabetic patients--thus limiting one of the pathogenic factors of diabetic foot and potentially preventing disabilit

Antibody dependent cellular cytotoxicity-inducing anti-EGFR antibodies as effective therapeutic option for cutaneous melanoma resistant to BRAF inhibitors

Introduction: About 50% of cutaneous melanoma (CM) patients present activating BRAF mutations that can be effectively targeted by BRAF inhibitors (BRAFi). However, 20% of CM patients exhibit intrinsic drug resistance to BRAFi, while most of the others develop adaptive resistance over time. The mechanisms involved in BRAFi resistance are disparate and globally seem to rewire the cellular signaling profile by up-regulating different receptor tyrosine kinases (RTKs), such as the epidermal growth factor receptor (EGFR). RTKs inhibitors have not clearly demonstrated anti-tumor activity in BRAFi resistant models. To overcome this issue, we wondered whether the shared up-regulated RTK phenotype associated with BRAFi resistance could be exploited by using immune weapons as the antibody-dependent cell cytotoxicity (ADCC)-mediated effect of anti-RTKs antibodies, and kill tumor cells independently from the mechanistic roots. Methods and results: By using an in vitro model of BRAFi resistance, we detected increased membrane expression of EGFR, both at mRNA and protein level in 4 out of 9 BRAFi-resistant (VR) CM cultures as compared to their parental sensitive cells. Increased EGFR phosphorylation and AKT activation were observed in the VR CM cultures. EGFR signaling appeared dispensable for maintaining resistance, since small molecule-, antibody- and CRISPR-targeting of EGFR did not restore sensitivity of VR cells to BRAFi. Importantly, immune-targeting of EGFR by the anti-EGFR antibody cetuximab efficiently and specifically killed EGFR-expressing VR CM cells, both in vitro and in humanized mouse models in vivo, triggering ADCC by healthy donors' and patients' peripheral blood cells. Conclusion: Our data demonstrate the efficacy of immune targeting of RTKs expressed by CM relapsing on BRAFi, providing the proof-of-concept supporting the assessment of anti-RTK antibodies in combination therapies in this setting. This strategy might be expected to concomitantly trigger the crosstalk of adaptive immune response leading to a complementing T cell immune rejection of tumors

Developing the ArchAIDE Application: A digital workflow for identifying, organising and sharing archaeological pottery using automated image recognition

Pottery is of fundamental importance for understanding archaeological contexts, facilitating the understanding of production, trade flows, and social interactions. Pottery characterisation and the classification of ceramics is still a manual process, reliant on analogue catalogues created by specialists, held in archives and libraries. The ArchAIDE project worked to streamline, optimise and economise the mundane aspects of these processes, using the latest automatic image recognition technology, while retaining key decision points necessary to create trusted results. Specifically, ArchAIDE worked to support classification and interpretation work (during both fieldwork and post-excavation analysis) with an innovative app for tablets and smartphones. This article summarises the work of this three-year project, funded by the European Union's Horizon 2020 Research and Innovation Programme under grant agreement N.693548, with a consortium of partners representing both the academic and industry-led ICT (Information and Communications Technology) domains, and the academic and development-led archaeology domains. The collaborative work of the archaeological and technical partners created a pipeline where potsherds are photographed, their characteristics compared against a trained neural network, and the results returned with suggested matches from a comparative collection with typical pottery types and characteristics. Once the correct type is identified, all relevant information for that type is linked to the new sherd and stored within a database that can be shared online. ArchAIDE integrated a variety of novel and best-practice approaches, both in the creation of the app, and the communication of the project to a range of stakeholders

Long-term preservation of kidney function with SGLT-2 inhibitors versus comparator drugs in people with type 2 diabetes and chronic kidney disease

AimsChronic kidney disease (CKD) is a prevalent and serious complication of type 2 diabetes (T2D). This study aims to evaluate kidney outcomes in a real-world cohort of patients with T2D and CKD who received SGLT2 inhibitors (SGLT2i) or other glucose-lowering medications (GLM).Materials and MethodsThis retrospective, multicentre study analysed data from patients aged 18-80 years with T2D and CKD, who initiated an SGLT2i or other GLM between 2015 and 2020. The primary outcome was the change in estimated glomerular filtration rate (eGFR) over time. Secondary outcomes included albuminuria changes and adverse kidney events. Propensity score matching was used to balance baseline characteristics between the two groups.ResultsAfter matching (n = 2020/group), patients (100% T2D with CKD) had a mean age of 63 years, BMI 32 kg/m2, HbA1c 8.2%. New-users of SGLT2i exhibited a slower decline in eGFR compared with new users of comparators (mean difference 1.43 mL/min/1.73 m2; p = 0.048). Albuminuria improved significantly more in the SGLT2i group, with a greater likelihood of category improvement (hazard ratio [HR] 1.17; p = 0.007). SGLT2i initiation was associated with a lower incidence of kidney outcomes, including a &gt;= 40% eGFR reduction (HR 0.63; p = 0.004). When the comparison was restricted to SGLT2i versus GLP-1RA (n = 1266/group), the eGFR slope was significantly better with SGLT2i (mean difference 0.62 mL/min/1.73 m2/year; p = 0.046).ConclusionsIn this large, real-world cohort, initiation of SGLT2i was associated with a significantly slower decline in kidney function and improved albuminuria compared with other diabetes drugs, including GLP-1RA. These findings support SGLT2i as the most effective T2D treatment to slow CKD progression