Effect of a multidisciplinary team approach in patients with diabetic foot ulcers on major adverse limb events (MALEs): systematic review and meta-analysis for the development of the Italian guidelines for the treatment of diabetic foot syndrome.

The treatment of patients with diabetic foot ulcers (DFUs) is extremely complex, requiring a comprehensive approach that involves a variety of different healthcare professionals. Several studies have shown that a multidisciplinary team (MDT) approach is useful to achieve good clinical outcomes, reducing major and minor amputation and increasing the chance of healing. Despite this, the multidisciplinary approach is not always a recognized treatment strategy. The aim of this meta-analysis was to assess the effects of an MDT approach on major adverse limb events, healing, time-to-heal, all-cause mortality, and other clinical outcomes in patients with active DFUs. The present meta-analysis was performed for the purpose of developing Italian guidelines for the treatment of diabetic foot with the support of the Italian Society of Diabetology (Società Italiana di Diabetologia, SID) and the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD). The study was performed using the Grading of Recommendations Assessment, Development, and Evaluation approach. All randomized clinical trials and observational studies, with a duration of at least 26 weeks, which compared the MDT approach with any other organizational strategy in the management of patients with DFUs were considered. Animal studies were excluded. A search of Medline and Embase databases was performed up until the May 1st, 2023. Patients managed by an MDT were reported to have better outcomes in terms of healing, minor and major amputation, and survival in comparison with those managed using other approaches. No data were found on quality of life, returning-to-walking, and emergency admission. Authors concluded that the MDT may be effective in improving outcomes in patients with DFUs.

Bypass surgery versus endovascular revascularization for occlusive infrainguinal peripheral artery disease: a meta-analysis of randomized controlled trials for the development of the Italian Guidelines for the treatment of diabetic foot syndrome.

To report a review and meta-analysis of all randomized controlled trials (RCTs) comparing bypass surgery (BS) and endovascular treatment (ET) in infrainguinal peripheral arterial disease (PAD) for several endpoints, such as major and minor amputation, major adverse limb events (MALEs), ulcer healing, time to healing, and all-cause mortality to support the development of the Italian Guidelines for the Treatment of Diabetic Foot Syndrome (DFS). A MEDLINE and EMBASE search was performed to identify RCTs, published since 1991 up to June 21, 2023, enrolling patients with lower limb ischemia due to atherosclerotic disease (Rutherford I-VI). Any surgical BS or ET was allowed, irrespective of the approach, route, or graft employed, from iliac to below-the-knee district. Primary endpoint was major amputation rate. Secondary endpoints were amputation-free survival major adverse limb events (MALEs), minor amputation rate, all-cause mortality, ulcer healing rate, time to healing, pain, transcutaneous oxygen pressure (TcPO2) or ankle-brachial index (ABI), quality of life, need for a new procedure, periprocedural serious adverse events (SAE; within 30 days from the procedure), hospital lenght of stay, and operative time. Twelve RCTs were included, one enrolled two separate cohorts of patients, and therefore, the studies included in the analyses were 13. Participants treated with ET had a similar rate of major amputations to participants treated with BS (MH-OR 0.85 [0.60, 1.20], p = 0.36); only one trial reported separately data on patients with diabetes (N = 1), showing no significant difference between ET and BS (MH-OR: 0.67 [0.09, 5.13], p = 0.70). For minor amputation, no between-group significant differences were reported: MH-OR for ET vs BS: 0.83 [0.21, 3.30], p = 0.80). No significant difference in amputation-free survival between the two treatment modalities was identified (MH-OR 0.94 [0.59, 1.49], p = 0.80); only one study reported subgroup analyses on diabetes, with a non-statistical trend toward reduction in favor of ET (MH-OR 0.62 [0.37, 1.04], p = 0.07). No significant difference between treatments was found for all-cause mortality (MH-OR for ET vs BS: 0.98 [0.80, 1.21], p = 0.88). A significantly higher rate of MALE was reported in participants treated with ET (MH-OR: 1.44 [1.05, 1.98], p = 0.03); in diabetes subgroup analysis showed no differences between-group for this outcome (MH-OR: 1.34 [0.76, 2.37], p = 0.30). Operative duration and length of hospital stay were significantly shorter for ET (WMD: - 101.53 [- 127.71, - 75.35] min, p < 0.001, and, - 4.15 [- 5.73, - 2.57] days, p < 0.001 =, respectively). ET was associated with a significantly lower risk of any SAE within 30 days in comparison with BS (MH-OR: 0.60 [0.42, 0.86], p = 0.006). ET was associated with a significantly higher risk of reintervention (MH-OR: 1.57 [1.10, 2.24], p = 0.01). No significant between-group differences were reported for ulcer healing (MH-OR: 1.19 [0.53, 2.69], p = 0.67), although time to healing was shorter (- 1.00 [0.18, 1.82] months, p = 0.02) with BS. No differences were found in terms of quality of life and pain. ABI at the end of the study was reported by 7 studies showing a significant superiority of BS in comparison with ET (WMD: 0.09[0.02; 0.15] points, p = 0.01). The results of this meta-analysis showed no clear superiority of either ET or BS for the treatment of infrainguinal PAD also in diabetic patients. Further high-quality studies are needed, focusing on clinical outcomes, including pre-planned subgroup analyses on specific categories of patients, such as those with diabetes and detailing multidisciplinary team approach and structured follow-up.

Development of the Italian clinical practice guidelines for the treatment of diabetic foot syndrome: design and methodological aspects.

AIMS: Diabetic foot syndrome (DFS) and its complications are a growing public health concern. The Italian Society of Diabetology (SID) and the Italian Association of Clinical Diabetologists (AMD), in collaboration with other scientific societies, will develop the first Italian guidelines for the treatment of DFS. METHODS: The creation of SID/AMD Guidelines is based on an extended work made by 19 panelists and 12 members of the Evidence Review Team. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology has been used to decide aims, reference population, and target health professionals. Clinical questions have been created using PICO (Patient, Intervention, Comparison, Outcome) conceptual framework. The definition of questions has been performed using a two-step web-based Delphi methodology, a structured technique aimed at obtaining by repeated rounds of questionnaires a consensus opinion from a panel of experts in areas wherein evidence is scarce or conflicting, and opinion is important. RESULTS: The mean age of panelists (26.3% women) was 53.7 ± 10.6 years. The panel proposed 34 questions. A consensus was immediately reached for all the proposed questions, 32 were approved and 2 were rejected. CONCLUSIONS: The areas covered by clinical questions included diagnosis of ischemia and infection, treatment of ischemic, neuropathic, and infected ulcers, prevention of foot ulceration, organization and education issues, and surgical management. The PICO presented in this paper are designed to provide indications for healthcare professionals in charge of diabetic foot treatment and prevention, primarily based on clinical needs of people with diabetic foot syndrome and considering the existing organization of health care.

Do Patients With Atypical Parathyroid Adenoma Need Close Follow-up?

CONTEXT: Atypical parathyroid adenomas (APAs) are neoplasms with uncertain malignant potential but lack unequivocal histological signs of malignancy. OBJECTIVE: This work aims to retrospectively evaluate the clinical and biochemical profiles of patients with APA, the outcome after parathyroidectomy (PTX), and the presence of CDC73 germline and somatic mutations. METHODS: This monocentric study was conducted on consecutive patients undergoing PTX for primary hyperparathyroidism (PHPT) between June 2000 and December 2020. Fifty-eight patients with a confirmed histopathological diagnosis of APA, and age- and sex-matched controls with parathyroid adenoma (PA) were also included. RESULTS: Fifty-four patients had sporadic PHPT and 4 had familial isolated hyperparathyroidism (FIHP). Thirty-four patients (59%) had symptomatic disease. Serum calcium and parathyroid hormone (PTH) levels were significantly higher in symptomatic compared to asymptomatic patients (P = .048 and .008, respectively). FIHP patients were younger than their sporadic counterparts (30 ±â€…17 years vs 55 ±â€…13 years). APA patients had significantly higher serum calcium and PTH levels and lower 25-hydroxyvitamin D concentration, bone mineral density, and T score at one-third distal radius compared to those with PA. Four of 56 APA patients displayed a CDC73 germline mutation. No somatic CDC73 mutation was identified in 24 tumor specimens. The mean follow-up after surgery was 60 ±â€…56.4 months. All but 6 patients (90%), 5 with apparently sporadic PHPT and 1 with FIHP, were cured after surgery. CONCLUSION: The large majority of patients with APA, despite a moderate/severe phenotype, have a good prognosis. Germline CDC73 mutation-positive patients had a higher rate of persistent/recurrent disease. CDC73 gene alterations do not seem to have a relevant role in the tumorigenesis of sporadic APA.

Pseudohypoparathyroidism: Focus on Cerebral and Renal Calcifications.

CONTEXT: Pseudohypoparathyroidism (PHP) is a group of disorders characterized by hypocalcemia, hyperphosphatemia, and elevated parathyroid hormone (PTH) levels as a result of end-organ resistance to PTH. OBJECTIVE: To describe a cohort of 26 patients with PHP followed in a single tertiary center. METHODS: Clinical, biochemical, radiological, and genetic analysis of the GNAS gene in 26 patients recruited since 2002. RESULTS: Ten patients harbored a GNAS mutation, 15 epigenetic abnormalities at the GNAS locus, and 1 did not show genetic or epigenetic abnormalities. According to clinical, biochemical, and genetic features, patients were classified as PHP1A, PHP1B, and pseudopseudohypoparathyroidism. Patients with PHP1A had an earlier diagnosis and more cases with family history, Albright hereditary osteodystrophy (AHO) features, hormonal resistance, and hypertension. Obesity was a common feature. No difference in biochemical values was present among PHP1A and PHP1B. Intracerebral calcification occurred in 72% of patients with no difference among PHP1A and PHP1B subgroups. No significant difference was observed between patients with and without intracerebral calcification for the time-weighted average values of total serum calcium, phosphate, calcium-phosphate product, and PTH fold increase. A borderline association between cerebral calcification and age at the time of diagnosis (P = .04) was found in the whole cohort of patients. No renal calcifications were found in the overall cohort. CONCLUSION: Patients with PHP1A more frequently have AHO features as well as hypertension than patients with PHP1B. Patients with PHP presented a high rate of intracerebral calcification with no significant difference between subgroups. No increased risk of renal calcifications was also found in the entire cohort.

COVID-19 in people with diabetes: understanding the reasons for worse outcomes.

Since the initial COVID-19 outbreak in China, much attention has focused on people with diabetes because of poor prognosis in those with the infection. Initial reports were mainly on people with type 2 diabetes, although recent surveys have shown that individuals with type 1 diabetes are also at risk of severe COVID-19. The reason for worse prognosis in people with diabetes is likely to be multifactorial, thus reflecting the syndromic nature of diabetes. Age, sex, ethnicity, comorbidities such as hypertension and cardiovascular disease, obesity, and a pro-inflammatory and pro-coagulative state all probably contribute to the risk of worse outcomes. Glucose-lowering agents and anti-viral treatments can modulate the risk, but limitations to their use and potential interactions with COVID-19 treatments should be carefully assessed. Finally, severe acute respiratory syndrome coronavirus 2 infection itself might represent a worsening factor for people with diabetes, as it can precipitate acute metabolic complications through direct negative effects on ß-cell function. These effects on ß-cell function might also cause diabetic ketoacidosis in individuals with diabetes, hyperglycaemia at hospital admission in individuals with unknown history of diabetes, and potentially new-onset diabetes.

Hypomagnesuria is Associated With Nephrolithiasis in Patients With Asymptomatic Primary Hyperparathyroidism.

CONTEXT: The pathogenesis of nephrolithiasis in primary hyperparathyroidism (PHPT) remains to be elucidated. The latest guidelines suggest parathyroidectomy in patients with asymptomatic PHPT with hypercalciuria (> 400 mg/d) and increased stone risk profile. OBJECTIVE: The objective of this work is to evaluate the association of urinary stone risk factors and nephrolithiasis in patients with asymptomatic sporadic PHPT and its clinical relevance. DESIGN: A total of 157 consecutive patients with sporadic asymptomatic PHPT were evaluated by measurement of serum and 24-hour urinary parameters and kidney ultrasound. RESULTS: Urinary parameters were tested in the univariate analysis as continuous and categorical variables. Only hypercalciuria and hypomagnesuria were significantly associated with nephrolithiasis in the univariate and multivariate analysis adjusted for age, sex, body mass index, estimated glomerular filtration rate, parathyroid hormone, 25-hydroxyvitamin D, serum calcium, and urine volume (odds ratio, OR 2.14 [1.10-4.56]; P = .04; OR 3.06 [1.26-7.43]; P = .013, respectively). Hypomagnesuria remained associated with nephrolithiasis in the multivariate analysis (OR 6.09 [1.57-23.5], P = .009) even when the analysis was limited to patients without concomitant hypercalciuria. The urinary calcium/magnesium (Ca/Mg) ratio was also associated with nephrolithiasis (univariate OR 1.62 [1.27-2.08]; P = .001 and multivariate analysis OR 1.74 [1.25-2.42], P = .001). Hypomagnesuria and urinary Ca/Mg ratio had a better, but rather low, positive predictive value compared with hypercalciuria. CONCLUSIONS: Hypomagnesuria and urinary Ca/Mg ratio are each associated with silent nephrolithiasis and have potential clinical utility as risk factors, besides hypercalciuria, for kidney stones in asymptomatic PHPT patients. The other urinary indices that have been commonly thought to be associated with kidney stones in PHPT are not supported by our results.