High-fat diet, adipokines and low-grade inflammation are associated with disrupted tendon healing: a systematic review of preclinical studies.

BACKGROUND: The aetiopathogenesis of tendinopathy is uncertain, but inflammation may play a role in the early phase of tendinopathy and in tendon healing response. We investigated the most up-to-date evidence about the association between obesity, high-fat diet and tendinopathy, focusing on the role of adipokines, inflammatory pathways and molecular changes. SOURCES OF DATA: A systematic review was performed searching PubMed, Embase and Cochrane Library databases following the PRISMA guidelines. We included studies of any level of evidence published in peer-reviewed journals. The risk of bias (SIRCLE) was assessed, as was the methodological quality (CAMARADES) of the included studies. We excluded all the articles with a high risk of bias and/or low quality after the assessment. After applying the inclusion and exclusion criteria, we included 14 studies of medium or high quality. AREAS OF AGREEMENT: A high-fat diet negatively affects tendon quality, increasing the risk of rupture and tendinopathy. AREAS OF CONTROVERSY: Controversial evidence exists on both tendon fat infiltration secondary to a dysregulation of the lipid metabolism and of a molecular effect of inflammatory pathways. GROWING POINTS: The secretion of adipokines is strictly related to fat ingestion and body composition and can potentially act on tendon physiology and injury. AREAS TIMELY FOR DEVELOPING RESEARCH: Adipokines, low-grade inflammation and fat intake play a role in disrupting tendon healing and setting up tendinopathy. Further high-quality research is needed to better define the molecular pathways involved.

Obesity Increases the Risk of Tendinopathy, Tendon Tear and Rupture, and Postoperative Complications: A Systematic Review of Clinical Studies.

BACKGROUND: Inflammation and mechanical demands play a role in the development of tendon conditions and the dysregulation of tendon healing. In patients with obesity, high levels of pro-inflammatory cytokines and a high mechanical demand promote chronic low-grade inflammation. Although controversial results have been reported, we aimed to summarize current evidence while highlighting the role of obesity in tendinopathy. QUESTIONS/PURPOSES: (1) Do patients with obesity have a greater risk of tendinopathy, stratified by upper and lower extremity sites, than patients who do not have obesity? (2) Is obesity associated with a higher risk of upper and lower extremity tendon tear and ruptures? (3) Is obesity associated with an increased risk of complications after upper and lower extremity tendon surgery? METHODS: We performed a systematic review by searching the PubMed, Embase, and Cochrane Library databases, combining the term "tendon" with common terms for tendinopathy and rupture such as "tendon injury OR tendinopathy OR tendon rupture" and "obese" OR "obesity." We included studies with any level of evidence published from January 2000 to July 10, 2019 in peer-reviewed journals reporting clinical results. After we removed the duplicates, there were 365 records. Two independent authors screened these records and excluded 320 based on abstract and title screening. Of the remaining 45 studies, 23 were excluded because the topic did not address the research questions (n = 19), the article was outdated (n = 3), or because there was a serious risk of bias (n = 1). Finally, we included 22 studies with 49,914 participants (5984 with obesity), 31,100 (1884 with obesity) of whom had upper-extremity tendinopathy, while 18,814 (4010 with obesity) had lower-extremity tendinopathy. Obesity was defined as a BMI ≥ 30 kg/m according to the WHO's criteria. Data were extracted and analyzed critically. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were applied, and the risk of bias (ROBINS tool) of the studies was assessed, as was the methodological quality (Coleman score). The assessment was performed independently by two authors. Inter-rater agreement for the assessments of the risk of bias and methodological quality were 89% and 94%, respectively. All studies were observational, and most were retrospective case-control studies. Any discrepancy was discussed and solved by consensus. The articles had a moderate risk of bias (eight articles) or a low risk of bias (fourteen articles). We excluded one article because of a serious risk of bias. The mean (range) Coleman score was 53.5 (42-74). RESULTS: Obesity was associated with a greater risk of upper extremity tendinopathy (rotator cuff: odds ratio 1.25 [95% confidence interval 1.12 to 1.40]; p < 0.001; medial epicondylitis: OR 1.9 [95% CI 1.0 to 3.7]; p < 0.05) and lower-extremity tendinopathy (Achilles tendon: OR 3.81 [95% CI 2.57 to 5.63]; OR 3.77 [95% CI 2.24 to 6.34]; OR 6.56 [95% CI 3.18 to 13.55], for obesity Classes I, II and III, respectively; patellar tendon: OR 1.10 [95% CI 1.05 to 1.90]; p = 0.001; plantar fascia: OR 2.97 [95% CI 1.64 to 5.37]; p = 0.004). Obesity was associated with a greater risk of upper extremity tendon tear (rotator cuff: OR 2.35 [95% CI 1.62 to 3.40]; p < 0.001) and rupture leading to tendon surgery (rotator cuff in men: OR 3.13 [95% CI 1.29 to 7.61]; p < 0.001 and women: OR 3.51 [95% CI 1.80 to 6.85]; p < 0.001). However, no association was found between BMI and lower extremity rupture (Achilles mean BMI: 27.77 kg/m [95% CI 26.94 to 28.49] versus control: 26.66 kg/m [95% CI 26.06 to 27.27]; p = 0.047). Upper extremity complications (n = 359) after tendon repair surgery had a weighted incidence of 13.27% and 8.13% for rotator cuff surgery in patients with and without obesity, respectively. In the lower extremity (n = 21,152), the weighted incidence for Achilles tendon surgery was 11.28% and 8.6% in patients with and without obesity, respectively. CONCLUSIONS: Obesity is associated with a higher risk of tendinopathy, tendon tear and rupture, and complications after tendon surgery than non-obesity. However, the high heterogeneity and observational nature of the studies highlight the need to be cautious about the results of our study. We encourage researchers to perform clinical and preclinical studies to explore pathways related to the metabolic state of this population. LEVEL OF EVIDENCE: Level IV, prognostic study.

Enhancing lymphoma diagnosis on core needle biopsies: Integrating immunohistochemistry with flow cytometry.

Image-guided core needle biopsies (IG-CNB) represent a minimally invasive approach for obtaining tissue in patients with lymphadenopathy and suspected lymphoma. Despite their utility, diagnostic challenges persist, with lower efficacy compared with excisional biopsies. Our study aimed to evaluate the potential utility of incorporation of flow cytometry (FC) alongside immunohistochemistry (IHC) when performing IG-CNB for suspected lymphoproliferative diseases. Analyzing 170 consecutive cases, guided by ultrasound (n = 94) or computer tomography (n = 76), we employed a diagnostic algorithm, already established in our laboratory practice, utilizing three antibody cocktail-equipped tubes tailored for defining lymphomas, particularly those of B-cell origin. FC expedited the diagnostic process, yielding presumptive results in 87.6% of cases within 48 h, with a positive predictive value of 98%. Addition of FC to routine IHC enhanced the diagnostic rate from 91.2% to 95.3%, reducing IG-CNB failure rate by 45%, from 8.8% to 4.7%. This enhancement was particularly notable for deep-seated sites and in the setting of suspected disease recurrences. Consequently, FC emerges as a valuable adjunctive tool, allowing for the improvement of diagnostic performance, with a particular focus on the ability to quantify the expression of surface markers for targeted therapies, and holding the potential to diminish the necessity for repeat excisional biopsies subsequent to IG-CNB procedures.

Expected and Observed Glomerular Filtration Rates in Kidney Transplant Patients Converted to Once Daily Tacrolimus: 10 Years of Follow-up.

The decline of allograft kidney function in the long term remains a significant issue in renal transplantation, with drug nephrotoxicity and cardiovascular complications as important risk factors. Our study aimed to evaluate the estimated glomerular filtration rate (eGFR) trend and metabolic cardiovascular risk factors over 10 years in a cohort of kidney transplant (KT) recipients converted from twice-daily (TD) tacrolimus (Tac) to once-daily (OD)-Tac. We enrolled 55 consecutive KT recipients who had been at the outpatient clinic between 2009 and 2011. Thirty-seven reached the 10-year follow-up. We compared the observed eGFR with the expected eGFR trend described in KT-recipients and monitored blood pressure and metabolic cardiovascular risk factors. The observed eGFR remained stable throughout the complete follow-up (P = .188). The observed decline of eGFR was significantly lower compared with the expected decline for KT patients (P < .001). The blood pressure was maintained within target values. The monitoring of plasma glucose levels demonstrated the stability of median values (P = .686), as well as cholesterol level (P = .250), high-density lipoprotein (HDL) cholesterol (P = .294), and triglycerides (P = .592) throughout the follow-up. The monitoring of tacrolimus plasma level demonstrated that median trough levels remained constant (median values 4.4-5.5 ng/mL) throughout the entire follow-up period (P = .149). We suggest that the reasonable control of metabolic risk factors for cardiovascular disease over long-term follow-up may significantly contribute to the preservation of eGFR compared with the decline expected in KT recipients.

School and pre-school children with type 1 diabetes during Covid-19 quarantine: The synergic effect of parental care and technology.

INTRODUCTION: Management of Type 1 Diabetes (T1D) poses numerous challenges, especially for young children and their families. Parental care positively influencesthe outcomesofchildren with T1D, while there are often criticisms in school environment. The COVID-19 pandemic has forced children and parents to spend many hours at home and diabetes care has returned mainly in the hands of parents. AIM OF THE STUDY: To evaluate the effectiveness of exclusive return to parental care in pre-school and school children with T1D treated with Tandem Basal IQ system during the COVID-19 pandemic. PATIENTS AND METHODS: 22 children (M:F = 14:8) with T1D have been evaluated. We compared insulin and CGM data (TIR, TBR and TAR) of two periods: PRE-COV and IN-COV, in which children have transitioned from normal school attendance to the exclusive care of their parents. RESULTS: During the IN-COV period a significantly (p < 0.001) higher median value of TIR (66,41%) was observed as compared to PRE-COV period (61,45%). Patients also showed a statistically significant difference (p < 0.002) between the IN-COV period and the PRE-COV period as concerning the TAR metric: respectively 29,86 ± 10,6% vs 34,73 ± 12,8%. The difference between the bolus insulin doses was statistically significant (PRE-COV 5,3 IU/day, IN-COV 7,9 IU/day - p < 0.05). CONCLUSION: Our observational real-life study confirms the positive effect of parental care in T1D very young children and demonstrates that during the COVID-19 pandemic it was possible to obtain a good glycometabolic compensation despite the significant change in lifestyle.