Effects of biophysical stimulation in patients undergoing arthroscopic reconstruction of anterior cruciate ligament: prospective, randomized and double blind study

Pre-clinical studies have shown that treatment by pulsed electromagnetic fields (PEMFs) can limit the catabolic effects of pro-inflammatory cytokines on articular cartilage and favour the anabolic activity of the chondrocytes. Anterior cruciate ligament (ACL) reconstruction is usually performed by arthroscopic procedure that, even if minimally invasive, may elicit an inflammatory joint reaction detrimental to articular cartilage. In this study the effect of I-ONE PEMFs treatment in patients undergoing ACL reconstruction was investigated. The study end-points were (1) evaluation of patients’ functional recovery by International Knee Documentation Committee (IKDC) Form; (2) use of non-steroidal anti-inflammatory drugs (NSAIDs), necessary to control joint pain and inflammation. The study design was prospective, randomized and double blind. Sixty-nine patients were included in the study at baseline. Follow-up visits were scheduled at 30, 60 and 180 days, followed by 2-year follow-up interview. Patients were evaluated by IKDC Form and were asked to report on the use of NSAIDs. Patients were randomized to active or placebo treatments; active device generated a magnetic field of 1.5 mT at 75 Hz. Patients were instructed to use the stimulator (I-ONE) for 4 h per day for 60 days. All patients underwent ACL reconstruction with use of quadruple hamstrings semitendinosus and gracilis technique. At baseline there were no differences in the IKDC scores between the two groups. At follow-up visits the SF-36 Health Survey score showed a statistically significant faster recovery in the group of patients treated with I-ONE stimulator (P < 0.05). NSAIDs use was less frequent among active patients than controls (P < 0.05). Joint swelling resolution and return to normal range of motion occurred faster in the active treated group (P < 0.05) too. The 2-year follow-up did not shown statistically significant difference between the two groups. Furthermore for longitudinal analysis the generalized linear mixed effects model was applied to calculate the group × time interaction coefficient; this interaction showed a significant difference (P < 0.0001) between the active and placebo groups for all investigated variables: SF-36 Health Survey, IKDC Subjective Knee Evaluation and VAS. Twenty-nine patients (15 in the active group; 14 in the placebo group) underwent both ACL reconstruction and meniscectomy; when they were analysed separately the differences in SF-36 Health Survey scores between the two groups were larger then what observed in the whole study group (P < 0.05). The results of this study show that patient’s functional recovery occurs earlier in the active group. No side effects were observed and the treatment was well tolerated. The use of I-ONE should always be considered after ACL reconstruction, particularly in professional athletes, to shorten the recovery time, to limit joint inflammatory reaction and its catabolic effects on articular cartilage and ultimately for joint preservation

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P &lt; .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Fluorescent nanodiamonds as innovative delivery systems for MiR-34a replacement in breast cancer

Nanodiamonds are innovative nanocrystalline carbon particles able to deliver chemically conjugated miRNAs. In oncology, the use of miRNA-based therapies may represent an advantage, based on their ability to simultaneously target multiple intracellular oncogenic targets. Here, nanodiamonds were tested and optimized to deliver miR-34a, a miRNA playing a key role in inhibiting tumor development and progression in many cancers. The physical-chemical properties of nanodiamonds were investigated suggesting electrical stability and uniformity of structure and size. Moreover, we evaluated nanodiamond cytotoxicity on two breast cancer cell models and confirmed their excellent biocompatibility. Subsequently, nanodiamonds were conjugated with miR-34a, using the chemical crosslinker polyethyleneimine; real-time PCR analysis revealed a higher level of miR-34a in cancer cells treated with the different formulations of nanodiamonds than with commercial transfectant. A significant and early nanodiamond-miR-34a uptake was recorded by FACS and fluorescence microscopy analysis in MCF7 and MDA-MB-231 cells. Moreover, nanodiamond-miR-34a significantly inhibited both cell proliferation and migration. Finally, a remarkable anti-tumor effect of miR-34a-conjugated nanodiamonds was observed in both heterotopic and orthotopic murine xenograft models. In conclusion, this study provides a rationale for the development of new therapeutic strategies based on use of miR-34a delivered by nanodiamonds to improve the clinical treatment of neoplasms

Effect of centre volume on pathological outcomes and postoperative complications after surgery for colorectal cancer: results of a multicentre national study

Background: The association between volume, complications and pathological outcomes is still under debate regarding colorectal cancer surgery. The aim of the study was to assess the association between centre volume and severe complications, mortality, less-than-radical oncologic surgery, and indications for neoadjuvant therapy.Methods: Retrospective analysis of 16,883 colorectal cancer cases from 80 centres (2018-2021). Outcomes: 30-day mortality; Clavien-Dindo grade >2 complications; removal of >= 12 lymph nodes; non-radical resection; neoadjuvant therapy. Quartiles of hospital volumes were classified as LOW, MEDIUM, HIGH, and VERY HIGH. Independent predictors, both overall and for rectal cancer, were evaluated using logistic regression including age, gender, AJCC stage and cancer site.Results: LOW-volume centres reported a higher rate of severe postoperative complications (OR 1.50, 95% c.i. 1.15-1.096, P = 0.003). The rate of >= 12 lymph nodes removed in LOW-volume (OR 0.68, 95% c.i. 0.56-0.85, P = 12 lymph nodes removed was lower in LOW-volume than in VERY HIGH-volume centres (OR 0.57, 95% c.i. 0.41-0.80, P = 0.001). A lower rate of neoadjuvant chemoradiation was associated with HIGH (OR 0.66, 95% c.i. 0.56-0.77, P < 0.001), MEDIUM (OR 0.75, 95% c.i. 0.60-0.92, P = 0.006), and LOW (OR 0.70, 95% c.i. 0.52-0.94, P = 0.019) volume centres (vs. VERY HIGH).Conclusion: Colorectal cancer surgery in low-volume centres is at higher risk of suboptimal management, poor postoperative outcomes, and less-than-adequate oncologic resections. Centralisation of rectal cancer cases should be taken into consideration to optimise the outcomes