Obesity in Prediabetic Patients: Management of Metabolic Complications and Strategies for Prevention of Overt Diabetes.

Obesity and prediabetes affect a substantial part of the general population, but are largely underdiagnosed, underestimated, and undertreated. Prediabetes differs from diabetes only in the degree of hyperglycaemia consequent to the progressive decline in residual beta-cell function. Both prediabetes and diabetes occur as a consequence of insulin resistance that starts several years before the clinical onset of overt diabetes. Macrovascular complications in patients with diabetes are mainly caused by insulin resistance. This is why in prediabetes, the overall cardiovascular risk is, by all means, similar to that in patients with diabetes. It is important, therefore, to identify prediabetes and treat patients not only to prevent or delay the onset of diabetes, but to reduce the cardiovascular risk associated with prediabetes. This review provides an overview of the pathophysiology of prediabetes in patients with obesity and the progression toward overt diabetes. We have reviewed nutritional and pharmacological approaches to the management of obesity and reduced glucose tolerance, and the treatment of the major comorbidities in these patients, including hypertension, dyslipidaemia, and Metabolic dysfunction-associated Steatotic Liver Disease (MASLD), has also been reviewed. In patients with obesity and prediabetes, the nutritional approach is similar to that adopted for patients with obesity and diabetes; treatments of dyslipidaemia and hypertension also have the same targets compared to patients with diabetes. MASLD is a critical issue in these patients; in the prediabetic state, MASLD rarely progresses into fibrosis. This highlights the importance of the early recognition of this pathological condition before patients become diabetic when the risk of fibrosis is much higher. It is necessary to raise awareness of the clinical relevance of this pathological condition in order to prompt early intervention before complications occur. The single most important therapeutic goal is weight loss, which must be early and persistent.

Italian National Registry of Alopecia Areata: an epidemiological study of 699 Italian patients.

BACKGROUND: Alopecia areata (AA) is an organ-specific autoimmune disease that affects the hair follicles of the scalp and the rest of the body causing hair loss. Due to the unpredictable course of AA and the different degrees of severity of hair loss, only a few well-designed clinical studies with a low number of patients are available. Also, there is no specific cure, but topical and systemic anti-inflammatory and immune system suppressant drugs are used for treatment. The need to create a global registry of AA, comparable and reproducible in all countries, has recently emerged. An Italian multicentric electronic registry is proposed as a model to facilitate and guide the recording of epidemiological and clinical data and to monitor the introduction of new therapies in patients with AA. METHODS: The aim of this study was to evaluate the epidemiological data of patients with AA by collecting detailed information on the course of the disease, associated diseases, concomitant and previous events, and the clinical response to traditional treatments. Estimate the impact on the quality of life of patients. RESULTS: The creation of the National Register of AA has proven to be a valid tool for recording, with a standardized approach, epidemiological data, the trend of AA, response to therapies and quality of life. CONCLUSIONS: AA is confirmed as a difficult hair disease to manage due to its unpredictable course and, in most cases, its chronic-relapsing course, capable of having a significant impact on the quality of life of patients.

Alopecia Areata Occurring after COVID-19 Vaccination: A Single-Center, Cross-Sectional Study.

Limited data concerning the development of autoimmune skin diseases after COVID-19 vaccination are currently available. Recently, a few reports described the development, worsening or recurrence of alopecia areata after the administration of COVID-19 vaccines. High variability in terms of disease onset following vaccination as well as the heterogeneous topical and/or systemic treatment approaches have been described. Methods: All patient-related data and images were obtained as part of clinical routine. Diagnosis of alopecia areata was established according to clinical and trichoscopic findings, along with the exclusion of common differential diagnoses. Results. Twenty-four patients, 20 females (83.3%) and four males (16.7%), with a mean age of 39.1 years (age range: 14-66 years), were examined for the occurrence of alopecia areata within 16 weeks after COVID-19 vaccination. Out of 24, 14 patients (58.3%) experienced a patchy alopecia areata, while an extensive disease occurred in 10/24 patients (41.7%): six patients with whole scalp involvement (alopecia areata totalis) and four patients with the whole body affected (alopecia areata universalis). Twelve patients reported a history of autoimmune disease (50%). Treatment with topical corticosteroid was performed in almost all patients with patchy alopecia areata, whilst it was associated with systemic drugs (corticosteroids, minoxidil, cyclosporin) in the case of generalized alopecia areata and alopecia areata universalis. Mean baseline values of Severity of Alopecia Tool (SALT) score decreased from 43.4 to 36.6 after 12 weeks of treatment, with evidence of hair regrowth in 16/21 patients. Conclusion. This study described the occurrence of alopecia areata after COVID-19 vaccination and its management that implicates the use of both topical and systemic therapies.

A Multi-professional Approach for Transition of Care at Discharge in Hyperglycemic Inpatients with COVID-19: A Single Center Study.

BACKGROUND: The discharge from the hospital of insulin-treated hyperglycemic patients is always challenging. This is even more so in patients requiring glucocorticoid treatment, such as those with COVID-19. PATIENTS AND METHODS: A retrospective monocentric study of 23 inpatients was conducted with newly diagnosed or already known diabetes mellitus (DM) who were naïve to insulin treatment, and who were hospitalized with COVID-19 in non-critical settings and then discharged. Patients were followed up for one month after discharge for the management of insulin treatment by a multi-professional team through phone consultations. RESULTS: Insulin prescriptions at discharge were 24.6 ± 14 U/day injected in 2 ± 1.5 daily shots. A mean of three phone consultations was required. One month later, the mean insulin reduction was 1.5 ± 1.3 shots and 6 ± 5 U/day. All patients reached their glycemic target without hypoglycemic events, drop-outs, or readmissions. CONCLUSION: This study demonstrates the feasibility, efficacy, and safety of a multi-professional approach through telemedicine for managing DM patients after discharge during COVID-19.

Diabetes and Bone Involvement in Primary Hyperparathyroidism: Literature Review and Our Personal Experience.

Background: Primary hyperparathyroidism (PHPT) and type 2 diabetes mellitus (T2DM) are common endocrine disorders impacting on skeletal health, whose concomitant occurrence is becoming more frequent. Patients and Methods: We searched the PubMed database from the National Library of Medicine about the relationship between T2DM and its treatment and bone manifestations of PHPT. Thereafter, we retrospectively evaluated a consecutive series of 472 PHPT patients. Among them 55 were also affected by T2DM. At the diagnosis of PHPT we compared bone turnover markers and bone densitometry between 55 patients with and 417 without T2DM and in the former group according to antidiabetic treatment. Results: Few data are available about T2DM and PHPT bone involvement, studies about T2DM treatments and PHPT bone manifestations are lacking. Among patients with PHPT of our series, those with T2DM were older, had a lower prevalence of osteitis fibrosa cystica, higher lumbar and femoral T-scores than the remaining patients. No difference was disclosed among the diabetic patients according to ongoing antidiabetic treatment, even though modern treatments were under-represented. Conclusions: No clinical study specifically evaluated the impact of T2DM on bone involvement in PHPT. In our experience, diabetic patients resulted more frequently "mild asymptomatic" than non-diabetic patients and showed a lower prevalence of radiological PHPT bone manifestations. The treatment of T2DM does not seem to affect the biochemical or clinical features of PHPT in our series. Further studies are needed to fully disclose the influence of T2DM and antidiabetic treatment on bone health in patients with PHPT.

Persistence of Elevated Procalcitonin in a Patient with Coronavirus Disease 2019 Uncovered a Diagnosis of Medullary Thyroid Carcinoma.

OBJECTIVE: During the ongoing coronavirus disease 2019 pandemic, procalcitonin (PCT) levels have proven useful in assisting clinicians to diagnose bacterial superinfection. However, in the absence of signs of infection or at the resolution thereof, inappropriately and persistently high PCT levels may suggest and reveal the presence of other pathologies. We report a patient with severe acute respiratory syndrome coronavirus 2 pneumonia with initially elevated PCT levels that persisted during recovery, prompting the diagnosis of medullary thyroid carcinoma (MTC). METHODS: A 43-year-old man presented with a 2-day history of fever, sneezing, sore throat, and dry cough. His PCT was 94 ng/mL (normal value, 0.00-0.10 ng/mL), and he was positive for severe acute respiratory syndrome coronavirus 2 RNA. RESULTS: Empirical antibiotic therapy was administered for 7 days, but despite a clinical improvement, serum PCT remained high (84 ng/mL). Serum calcitonin (CTN) was 2120 pg/mL (normal, ≤12 pg/mL). Cytologic examination of thyroid nodules and CTN measurement of the aspiration needle washout confirmed MTC. The patient underwent total thyroidectomy with bilateral cervical lymph node dissection. Lowered CTN (986 pg/mL) and PCT (16 ng/mL) levels were observed 48 hours after surgery. A close follow-up was planned following the results of RET gene analysis. CONCLUSION: PCT can be a useful biochemical marker of MTC suspicion in patients with inflammatory conditions and persistently elevated PCT, even after resolution. In our case, high levels of PCT in a patient with coronavirus disease 2019 pneumonia without signs of bacterial infection led to MTC diagnosis.

Reflectance Confocal Microscopy Applied to Folliculitis Decalvans: Preliminary Results of a Multicenter Study.

Although trichoscopic criteria indicative of disease severity and inflammatory activity have been recently proposed, the potential use of reflectance confocal microscopy (RCM) in the evaluation of the inflammatory stage of FD has never been published to date. Our study investigated RCM features of 14 patients with a histopathological diagnosis of FD, evaluating clinical and trichoscopic findings. RCM findings were divided into 2 main patterns: "follicular" and "interfollicular." Our results suggest a potential role for RCM as a noninvasive, fast technique for a complementary investigation in the diagnostic process, as well as in the therapeutic management decision.

Predictors of recurrence of pheochromocytoma and paraganglioma: a multicenter study in Piedmont, Italy.

The available data on the natural history of pheochromocytomas and paragangliomas after radical surgery are heterogeneous and discordant. The aim of our retrospective multicenter study was to find predictors of recurrence in patients with pheochromocytomas and sympathetic paragangliomas submitted to radical surgery in Piedmont (a region in northwest Italy). We collected data from 242 patients diagnosed between 1990 and 2016. Forty-two patients (17.4%) had disease recurrence. Multivariate analysis showed that genetic mutation (HR = 3.62; 95% CI 1.44-9.13; p = 0.006), younger age (HR = 0.97; 95% CI 0.95-0.99; p = 0.031) and larger tumor size (HR = 1.01; 95% CI 1.00-1.02; p = 0.015) were independently associated with a higher recurrence risk of pheochromocytoma and paraganglioma; in pheochromocytomas, genetic mutation (HR = 3.4; 95% CI 1.00-11.48; p = 0.049), younger age (HR = 0.97; 95% CI 0.94-0.99; p = 0.02), higher tumor size (HR = 1.01; 95% CI 1.00-1.03; p = 0.043) and PASS value (HR = 1.16; 95% CI 1.03-1.3; p = 0.011) were associated with recurrence. Moreover, tumor size was the only predictor of metastatic pheochromocytoma and paraganglioma (HR = 4.6; 95% CI 1.4-15.0; p = 0.012); tumor size (HR = 3.93; 95% CI 1.2-16.4; p = 0.026) and PASS value (HR = 1.27; 95% CI 1.06-1.53; p = 0.007) were predictors of metastatic pheochromocytoma. In conclusion, our findings suggest that the recurrence of pheochromocytoma and sympathetic paraganglioma develops more frequently in younger subjects, patients with a family history of chromaffin tissue neoplasms, mutations in susceptibility genes, larger tumors and higher values of PASS. We recommend genetic testing in all patients with PPGL and strict follow-up at least on an annual basis.

Efficacy of topical beta-blockers in the management of EGFR-inhibitor induced paronychia and pyogenic granuloma-like lesions: case series and review of the literature.

Nail toxicities, such as paronychia and pyogenic granuloma-like lesions, are well-recognized side effects of epidermal growth factor receptor inhibitor (EGFR-I) therapy that can significantly impair patient's quality of life and compliance to anticancer treatment. Numerous therapeutic options are available, with variable rates of success. Recently, topical ß-blockers have emerged as a novel, non-invasive treatment strategy. We tested the effectiveness of topical timolol 0.5% gel, twice daily, under occlusion for 30 days, on paronychia and periungual pyogenic granuloma-like lesions in 9 patients being treated with EGFR-I. We also reviewed the available literature on this topic, which is the use of topical ß-blockers in the management of EGFR-I-induced nail toxicities. We assessed 25 lesions consistent with the diagnosis of EGFR-I-induced pyogenic granuloma-like lesions and paronychia (21 diagnosed as pyogenic granuloma-like, and four as paronychia). Thirteen of the 25 lesions achieved complete resolution, 9/25 reached at least improvement, and only 3/25 did not respond to the intervention. As for the review, four papers met the scope of our research. The results confirmed at least partial benefit in the majority of treated patients. Among current strategies, high-potency topical corticosteroids are a well-known treatment option especially for paronychia, targeting the inflammatory component of such lesions; nevertheless, the management of pyogenic granuloma-like lesion is often more complex and the success rate is variable. Nail plate avulsion and phenol chemical matricectomy are not highly effective and display some degree of invasiveness. Topical ß-blockers seem to be promising alternatives, especially in fragile cancer patients who may be unsuitable candidates for an invasive procedure.

Apulo-Calabrese and Crossbreed Pigs Show Different Physiological Response and Meat Quality Traits after Short Distance Transport.

Despite the increasing interest in the welfare of animals during transport, very little is known on the response of local pig breeds to the transport procedures. This study aims to compare the effect of short journey on behaviour, blood parameters, and meat quality traits in 51 Apulo-Calabrese and 52 crossbreed [Duroc × (Landrace × Large White)] pigs. All the animals were blood sampled five days before delivery (basal condition) and at exsanguination for the analysis of creatine kinase, cortisol, glucose, lactate, albumin, albumin/globulin, total protein, urea, creatinine, aspartate aminotransferase (AST), alanine aminotransferase, alkaline phosphate, sodium, and potassium. Post mortem pH, color, drip loss, cooking loss, and Warner-Bratzler shear force were measured at different times in longissimus thoracis samples. Univariate and multivariate analyses showed that glucose, albumin/globulin, urea, and AST at exsanguination were influenced by the genetic type. Apulo-Calabrese showed the highest increase in blood values of lactate, creatinine, sodium and potassium after the short distance transport. Behavioural occurrences were similar in both genetic types during unloading and lairage. Small differences were observed for meat quality although significantly higher a* and lower L* were found in Apulo-Calabrese pigs, showing meat with a deeper red colour than crossbreeds.

Two-Dimensional Electronic Spectroscopy Unravels sub-100 fs Electron and Hole Relaxation Dynamics in Cd-Chalcogenide Nanostructures.

We use two-dimensional electronic spectroscopy (2DES) to disentangle the separate electron and hole relaxation pathways and dynamics of CdTe nanorods on a sub-100 fs time scale. By simultaneously exciting and probing the first three excitonic transitions (S1, S2, and S3) and exploiting the unique combination of high temporal and spectral resolution of 2DES, we derive a complete picture for the state-selective carrier relaxation. We find that hot holes relax from the 1Σ3/2 to the 1Σ1/2 state (S2 → S1) with 30 ± 10 fs time constant, and the hot electrons relax from the Σ' to the Σ state (S3 → S1) with 50 ± 10 fs time constant. This observation would not have been possible with conventional transient absorption spectroscopy due to the spectral congestion of the transitions and the very fast relaxation time scales.

Nonlinear Carrier Interactions in Lead Halide Perovskites and the Role of Defects.

The simple solution processability at room temperature exposes lead halide perovskite semiconductors to a non-negligible level of unintentional structural and chemical defects. Ascertained that their primary optoelectronic properties meet the requirement for high efficiency optoelectronic technologies, a lack of knowledge about the nature of defects and their role in the device operation currently is a major challenge for their market-scale application due to the issues with stability and reliability. Here, we use excitation correlation photoluminescence (ECPL) spectroscopy to investigate the recombination dynamics of the photogenerated carriers in lead bromide perovskites and quantitatively describe the carrier trapping dynamics within a generalization of the Shockley-Read-Hall formalism. The superior sensitivity of our spectroscopic tool to the many-body interactions enables us to identify the energetics of the defects. In fact, in the case of polycrystalline films, depending on the synthetic route, we demonstrate the presence of both deep and shallow carrier traps. The shallow defects, which are situated at about 20 meV below the conduction band, dope the semiconductor, leading to a substantial enhancement of the photoluminescence quantum yield despite carrier trapping. At excitation densities relevant for lasing, we observe breakdown of the rate-equation model, indicating a buildup of a highly correlated regime of the photocarrier population that suppresses the nonradiative Auger recombination. Furthermore, we demonstrate that colloidal nanocrystals represent virtually defect-free systems, suffering from nonradiative quenching only due to subpicosecond Auger-like interactions at high excitation density. By correlating the fabrication conditions to the nonradiative loss channels, this work provides guidelines for material engineering towards superior optoelectronic devices.

Clinical predictors of nonresponse to anti-TNF-α agents in psoriatic patients: A retrospective study.

Although the heterogeneity of the therapeutic response to TNF-α blockers seems to be mainly due to genetic factors, several studies showed that a range of factors may influence it. The aim of our study was to investigate the impact of patients' demographic and clinical characteristics on primary response to an anti-TNF-α therapy in psoriatic patients. We retrospectively examined the relationship between various clinical and demographic features and response to treatment with etanercept, adalimumab, and infliximab, evaluated as PASI75 and average PASI improvement at weeks 12, 16, and 14, respectively. We analyzed data obtained from 199 patients. A better response to the treatment was significantly associated with male gender (OR = 2.59), coexistence of psoriatic arthritis (OR = 1.97), and PASI ≤15 at baseline (OR = 0.91). The present study supports that some clinical factors may be potential predictors of response to anti-TNF-α agents in psoriatic patients.