Kinetics of the SARS-CoV-2 Antibody Avidity Response Following Infection and Vaccination

Serological assays capable of measuring antibody responses induced by previous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been critical tools in the response to the COVID-19 pandemic. In this study, we use bead-based multiplex assays to measure IgG and IgA antibodies and IgG avidity to five SARS-CoV-2 antigens (Spike (S), receptor-binding domain (RBD), Nucleocapsid (N), S subunit 2, and Membrane-Envelope fusion (ME)). These assays were performed in several cohorts of healthcare workers and nursing home residents, who were followed for up to eleven months after SARS-CoV-2 infection or up to six months after vaccination. Our results show distinct kinetic patterns of antibody quantity (IgG and IgA) and avidity. While IgG and IgA antibody levels waned over time, with IgA antibody levels waning more rapidly, avidity increased with time after infection or vaccination. These contrasting kinetic patterns allow for the estimation of time since previous SARS-CoV-2 infection. Including avidity measurements in addition to antibody levels in a classification algorithm for estimating time since infection led to a substantial improvement in accuracy, from 62% to 78%. The inclusion of antibody avidity in panels of serological assays can yield valuable information for improving serosurveillance during SARS-CoV-2 epidemics.     

Monoclonal Antibody Specific for TIRC7 Induces Donor-specific Anergy and Prevents Rejection of Cardiac Allografts in Mice

T cell immune response c-DNA (TIRC7) is up-regulated during the early stages of T-cell activation in response to alloantigens. In this study, we analyzed the effects of newly developed monoclonal antibodies (mAb) against TIRC7 in acute cardiac allograft rejection. Fully vascularized heterotopic allogeneic heart transplantation was performed in mice across a full-mismatch barrier (C57Bl/10 into CBA). Recipients received seven injections (day 0-7) of a novel anti-TIRC7 mAb or remained untreated. Graft survival, histology and ex vivo lymphocyte functions were tested. Targeting of TIRC7 with an anti-TIRC7 mAb diminishes lymphocyte infiltration into grafts resulting in delay of morphological graft damage and prolongation of allograft survival. The lymphocytes from anti-TIRC7 mAb-treated animals exhibit hypo-responsiveness without evidence of lymphocyte depletion against the donor allo-antigens. Proliferation and expression of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) were down-regulated while interleukin-4 (IL-4) and IL-10 expression were spared. Moreover, anti-TIRC7 mAb enhanced up-regulation of CTLA-4 expression but suppressed up-regulation of CD25 on stimulated lymphocytes in vitro and in vivo. Ligation of TIRC7 has important effects on the regulation of co-stimulatory signaling pathways associated with suppressing of T-cell activation. Targeting of TIRC7 may therefore provide a novel therapeutic approach for modulating T cell immune responses during organ transplantation.     

808-nm laser therapy with a flat-top handpiece photobiomodulates mitochondria activities of <Emphasis Type="Italic">Paramecium primaurelia</Emphasis> (Protozoa)

Photobiomodulation is proposed as a non-linear process, and only low-level laser therapy (LLLT) is assumed to stimulate exposed cells, whereas high powered laser and fluences can cause negative effects, exhausting the cell’s energy reserve as a consequence of excessive photon-based stimulation. In our work, we investigated and compared the effects of 808-nm diode laser (CW) with a new flat-top handpiece. To this purpose, we tested the photobiomodulation effects of 1 and 3 J/cm² fluence, both generated by 100 mW or 1 W of laser power and of 64 J/cm² of fluence generated by 100 mW, 1 W, 1.5 W or 2 W, as expressed through oxygen consumption and ATP synthesis of Paramecium. Data collected indicates the incremental consumption of oxygen through irradiation with 3 J/cm²–100 mW or 64 J/cm²–1 W correlates with an increase in Paramecium ATP synthesis. The Paramecium respiration was inhibited by fluences 64 J/cm²–100 mW or 64 J/cm²–2 W and was followed by a decrease in the endogenous ATP concentration. The 1 J/cm²–100 mW or 1 W and 3 J/cm²–1 W did not affect mitochondrial activity. The results show that the fluence of 64 J/cm²–1 W more than the 3 J/cm²–100 mW causes greater efficiency in Paramecium mitochondria respiratory chain activity. Our results suggest that thanks to flat-top handpiece we used, high fluences by high-powered laser have to be reconsidered as an effective and non-invasive therapy. Possible associated benefits of deeper tissue penetration would increase treatment effectiveness and reduced irradiation time.     

Aortic valve replacement in severe aortic stenosis with left ventricular dysfunction: determinants of cardiac mortality and ventricular function recovery

Objective: The influence of left ventricular (LV) dysfunction on survival of patients with severe aortic stenosis is poorly characterized. Few data are available about preoperative predictors of cardiac mortality and LV function recovery after aortic valve replacement of such patients. The aim of our study was to examine the outcome and the preoperative predictors of postoperative cardiac death and of LV function recovery in these patients. Methods: We evaluated 85 consecutive patients with severe aortic stenosis (aortic valve area <1 cm²) and severe depression of LV ejection fraction (EF) <35% at cardiac catheterization. Among them, 52 underwent aortic valve replacement and they were compared to patients who were not operated on. All patients had a mean clinical follow-up of 53 months and 94% of them had a mean echocardiographic follow-up of 14 months after aortic valve replacement. Results: The mean baseline characteristics included: LVEF 28±6%, peak-to-peak transvalvular gradient 51±29 mmHg, aortic valve area 0.63±0.25 cm². Thirty-three patients did not undergo aortic valve replacement: 32 of them died within 3 years. Fifty-two patients underwent aortic valve replacement and 16 had a concomitant coronary bypass surgery. In-hospital mortality was 8%. Postoperative NYHA functional class changed from 2.84±0.67 to 1.43±0.44 (P<0.001) and LVEF from 29±6% to 43±10% (P<0.001). At follow-up 10 patients died of heart disease. By multivariate analysis, preoperative LV end-systolic volume index (ESVI) was the only covariate of cardiac death (LVESVI/10 ml/m², OR 1.3, CI 1.1–1.8, P<0.028). By using a receiver operating characteristic curve, LVESVI≤90 ml/m² was the best cut-off value (sensitivity and specificity 78%) to fit with a better survival (93% vs. 63%, P<0.01) and with LVEF recovery after aortic valve replacement (EF improved by 15±10% vs. 8±5%, P<0.001). Conclusions: Despite LV dysfunction, aortic valve replacement appears to change drastically the natural history of severe aortic stenosis. Preoperative LV levels predict different postoperative survival rate and LVEF recovery.     

Fluorine-18-fluorodeoxyglucose positron emission tomography in the preoperative assessment of thyroid nodules in an endemic goiter area

BACKGROUND: The aim of this study was to evaluate the usefulness of fluorine-18-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) in the preoperative assessment of suspicious thyroid nodules. METHODS: A total of 43 patients were examined before surgical resection. In all patients, imaging was obtained at 70 minutes after the intravenous administration of 180 MBq (18)F-FDG. Standard uptake values (SUVs) were calculated. RESULTS: A total of 16 patients with thyroid carcinomas (11 papillary, 3 follicular, 2 anaplastic), 23 thyroid adenomas (11 microfollicular, 10 Hurthle cell, 2 macrofollicular), and 4 patients with degenerative goiter were found. (18)F-FDG uptake in Hurthle cell adenoma, thyroid cancer, microfollicular adenoma, degenerative goiter, and macrofollicular adenoma was 4.4 +/- 2.2, 3.7 +/- 1.9, 1.6 +/- 0.3, 1.2 +/- 0.2, and 0.9 +/- 0.1, respectively. Significant differences were observed between thyroid carcinomas and both microfollicular adenomas and degenerative goiters (P < 0.05), and between Hurthle cell adenomas and both microfollicular adenomas as well as degenerative goiter (P < 0.05). For diagnosis of thyroid carcinoma, 100% sensitivity, 63% specificity, and 100% negative predictive value was found when a cutoff value for SUV of 2 was used. CONCLUSIONS: Our results indicate that thyroid carcinomas, in contrast to most benign thyroid nodules, demonstrate significantly increased glucose metabolism. (18)F-FDG PET is unlikely to differentiate successfully all benign tumors from malignant tumors, but it can help select patients who need surgery, especially if cytology is inconclusive or malignancy cannot be excluded.     

Cognitive and functional outcomes of terror victims who suffered from traumatic brain injury

Primary objective: To describe the outcomes of terror victims suffered from traumatic brain injury (TBI).

Research design: Retrospective chart review of 17 terror and 39 non-terror TBI patients treated in a rehabilitation department during the same period.

Methods and procedure: Variables include demographic data, Injury Severity Scale (ISS), length of stay (LOS) and imaging results. ADL was measured using the Functional Independence Measurement (FIM), cognitive and memory functions were measured using the Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) battery and the Rivermead Battery Memory Test (RBMT), respectively.

Main outcome and results: Terror TBI patients were significantly younger, had higher ISS score and higher rates of intracerebral haemorrhage (ICH), brain surgery and penetrating brain injuries than the non-terror TBI group. There was no difference in mean LOS, mean FIM values, mean FIM gain and mean cognitive and memory improvement between groups. Terror victims suffered from a higher percentage of post-traumatic epilepsy (35% vs. 10%, p = 0.05), whereas the rate of PTSD and the rate of return to previous occupation were similar between groups.

Conclusions: Although TBI terror victims had more severe injury, they gained most of ADL functions and their rehabilitation outcomes were similar to non-terror TBI patients. These favourable results were achieved due to a comprehensive interdisciplinary approach to terror victims and also by national support which allowed an adequate period of treatment and sufficient resources as needed.     

Treatment of Hemorrhoids in Day Surgery: Stapled Hemorrhoidopexy vs Milligan–Morgan Hemorrhoidectomy

Background Recently, it has been demonstrated that surgical treatment of hemorrhoids in a day-care basis is possible and safe. The aim of this study was to compare the Longo stapled hemorrhoidopexy (SH) and the Milligan–Morgan hemorrhoidectomy (MMH). Methods One hundred seventy one patients (95 cases in SH group and 76 cases in MMH group) entered the study: 83 cases were III degree hemorrhoids, 88 IV degree. A priori and a post hoc power analysis were performed. Results, prospectively collected, were compared using chi squared test and student t test. Visual analog scale was used for pain evaluation. Postoperative pain, duration of pain, wound secretion, bleeding, resumption of a normal lifestyle, and postoperative complication were evaluated. Results Surgical time was 28.41 ± 10.78 for MMH and 28.30 ± 13.28 min in SH (P = 0.94). Postoperative pain was not different between MMH and SH during the first two postoperative days (4.73 ± 2.91 vs 5.1 ± 3.048; P = 0.4), during the following 6 days, patients treated with SH had less pain (4.63 ± 2.04 in MMH vs 3.60 ± 2.35 in SH; P = 0.006). In the SH group, seven patients needed further hospital stay for complicated course. SH showed higher incidence of anal fissure compared with MMH (6.3% vs 0%; P = 0.025) but no differences in urinary retention, anal stricture, urgency, or anal hemorrhage. Conclusions This study confirms that SH is associated with less postoperative pain and shorter postoperative symptoms, compared with MMH. SH may be a viable addition to the therapy for hemorrhoids with some advantages in early postoperative pain and some disadvantages in postoperative complications and costs.     

Papillary Thyroid Carcinoma: Factors Influencing Recurrence and Survival

Background The prognosis of patients with papillary thyroid carcinoma (PTC) is usually favorable; however, a subset of patients can develop local recurrence or distant metastases. The aim of this study was to evaluate the prognostic factors influencing the recurrence and the survival rate in 950 PTC patients. Materials and Methods From 1990 to 2005, 950 consecutive patients affected by PTC were operated on at our Department. We analyzed the prognostic role of the following parameters: gender, age at initial treatment, extent of thyroid surgery, node dissection, tumor size, node metastases, distant metastases, stage, and 131-I therapy. Results Seventy-nine patients (8.3%) developed locoregional or distant metastases after an average follow-up of 7.8 years (range 2–17 years); in particular local recurrence was observed in 25 cases and distant metastases in 54 cases. The global 10- and 15-year survival rates were 91.38% and 88.69%, respectively. At univariate analysis, all variables were significantly correlated with recurrence (P = .001) except gender (P = .3); moreover, gender (P = .2), node dissection (P = .5), and node metastases (P = .06) were not significant on 10- and 15-year survival. At multivariate analysis the age at first treatment, T4, M+, stage IV, the extent of thyroid surgery, and the 131-I therapy resulted to be significant and independent prognostic factors (P < .001). Conclusion Our data, in disagreement with other staging systems, suggest that gender does not play a significant role both in recurrence and survival. Moreover, the 131-I therapy was a statistically significant prognostic factor at univariate and multivariate analyses.     

Genetic variation, C-reactive protein levels, and incidence of diabetes

C-reactive protein (CRP) has been shown to be associated with type 2 diabetes, but whether CRP has a causal role is not yet clear. We examined the association in the Rotterdam Study, a population-based prospective cohort study. The association of baseline serum CRP and incident diabetes during follow-up was investigated, and a meta-analysis was conducted on the BMI-adjusted relation of CRP and diabetes. Furthermore, the association of CRP haplotypes with serum CRP and risk of diabetes was assessed. The age- and sex-adjusted hazard ratio for diabetes was 1.41 (95% CI 1.29-1.54) per 1 SD increase in natural logarithm of CRP, and it was 1.88, 2.16, and 2.83 for the second, third, and fourth quartiles of CRP, respectively, compared with the first quartile. The risk estimates attenuated but remained statistically significant after additional adjustment for obesity indexes, which agreed with the results of the meta-analysis. The most common genetic haplotype was associated with a significantly lower CRP level compared with the three other haplotypes. The risk of diabetes was significantly higher in the haplotype with the highest serum CRP level compared with the most common haplotype (OR 1.45, 95% CI 1.08-1.96). These findings support the hypothesis that serum CRP enhances the development of diabetes.