Leukocyte-Poor Platelet-Rich Plasma as an Adjuvant to Arthroscopic Rotator Cuff Repair Reduces the Retear Rate But Does Not Improve Functional Outcomes: A Double-Blind Randomized Controlled Trial.

BACKGROUND: Whether the use of PRP as an adjuvant of rotator cuff repairs leads to improved tendon healing and better functional outcomes remains unclear in clinical evidence. PURPOSE: The main purpose of this study was to assess whether the use of leukocyte-poor platelet-rich plasma (LP-PRP) as an adjuvant to arthroscopic rotator cuff repair (ARCR) decreases the rate of retears compared with a control group. The secondary objective was to analyze whether LP-PRP improves patient-reported outcomes. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: This was a double-blind randomized controlled trial at a single center. A consecutive series of 96 patients with rotator cuff tears <3 cm were enrolled and randomly allocated to the control group (double-row suture-bridge ARCR alone [n = 48]) and the PRP group (double-row suture-bridge repair, followed by 1 LP-PRP injection during surgery [n = 48]). The visual analog scale (VAS) for pain, the American Shoulder and Elbow Surgeons (ASES) score, the Single Assessment Numeric Evaluation (SANE), and the Pittsburgh Sleep Quality Index (PSQI) were administered preoperatively and at 6- and 12-month follow-up. Magnetic resonance imaging (MRI) was performed to evaluate tendon integrity at 6-month follow-up. Both patients and assessors were blinded to the intervention received during surgery. RESULTS: The mean patient age was 56.1 ± 2.98 years. Of the 96 patients, 90 had MRI performed at 6 months after surgery (94% radiological follow-up). The retear rate in the PRP group was 15.2% (7/46 [95% CI, 6%-28%]), which was lower than that in the control group of 34.1% (15/44 [95% CI, 20%-49%]) (P = .037). Therefore, the risk ratio of ruptures in patients exposed to LP-PRP was 0.44 (95% CI, 0.2-0.9; P = .037). Overall, the ASES, VAS, SANE, and PSQI scores showed a statistical improvement after surgery (P < .001). There were no significant differences in functional scores between the groups. Most of the patients exceeded the minimal clinically important difference for the ASES, SANE, and VAS without significant differences between the groups. CONCLUSION: In patients with rotator cuff tears <3 cm undergoing double-row suture-bridge repair, a 5-mL dose of LP-PRP injected at the tendon-bone interface significantly reduced the retear rate. However, the use of LP-PRP in terms of postoperative pain and patient-reported outcomes failed to show clinically meaningful effects. REGISTRATION: NCT04703998 (ClinicalTrials.gov identifier).

Substantial Variability in Platelet-Rich Plasma Composition Is Based on Patient Age and Baseline Platelet Count.

Purpose: To evaluate the effect of age, sex, body mass index (BMI), and baseline blood count on the final composition of platelet rich-plasma (PRP) and to evaluate the variability of PRP applied in the same patient at 2 different times. Methods: Potential subjects treated with PRP between January 2019 and December 2021 were identified in an institutional registry. Patient demographics and baseline blood count were prospectively recorded in a consecutive series of patients treated with PRP for a musculoskeletal condition in our Institution. The influence of sex, BMI, age, and baseline blood count on final platelet concentrations in PRP was evaluated. Finally, intrapersonal variability was evaluated. Results: A total of 403 PRP injections from 357 patients were analyzed from an institutional prospective registry of PRP between January 2019 and December 2021. A directly proportional variation in PRP platelet count of 3.8× was observed for each unit increase in baseline blood platelet count. For every decade increase, we observed an approximate decrease of 32,666 platelets. When the first dose of PRP platelet counts was compared with the second dose of PRP platelet counts between the same patients, significant differences were found. A mean of 890,018 platelets in the first PRP and a mean of 1,244,467 in the second PRP with a mean difference of 354,448 was found (P = .008). We did not find differences in the final concentration of platelets regarding sex, BMI, or PRP protocol. Conclusions: Overall the final composition of PRP (platelet count) was significantly influenced by patient's age and baseline platelet count. In contrast, BMI, sex and the rest of the components of the baseline blood count did not have a significant influence on final PRP. Furthermore, in patients who received 2 doses of PRP, the final concentration of platelets varied significantly between the 2 preparations. Level of Evidence: Level IV, prognostic case series.

A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia.

BACKGROUND: Convalescent plasma is frequently administered to patients with Covid-19 and has been reported, largely on the basis of observational data, to improve clinical outcomes. Minimal data are available from adequately powered randomized, controlled trials. METHODS: We randomly assigned hospitalized adult patients with severe Covid-19 pneumonia in a 2:1 ratio to receive convalescent plasma or placebo. The primary outcome was the patient's clinical status 30 days after the intervention, as measured on a six-point ordinal scale ranging from total recovery to death. RESULTS: A total of 228 patients were assigned to receive convalescent plasma and 105 to receive placebo. The median time from the onset of symptoms to enrollment in the trial was 8 days (interquartile range, 5 to 10), and hypoxemia was the most frequent severity criterion for enrollment. The infused convalescent plasma had a median titer of 1:3200 of total SARS-CoV-2 antibodies (interquartile range, 1:800 to 1:3200). No patients were lost to follow-up. At day 30 day, no significant difference was noted between the convalescent plasma group and the placebo group in the distribution of clinical outcomes according to the ordinal scale (odds ratio, 0.83; 95% confidence interval [CI], 0.52 to 1.35; P = 0.46). Overall mortality was 10.96% in the convalescent plasma group and 11.43% in the placebo group, for a risk difference of -0.46 percentage points (95% CI, -7.8 to 6.8). Total SARS-CoV-2 antibody titers tended to be higher in the convalescent plasma group at day 2 after the intervention. Adverse events and serious adverse events were similar in the two groups. CONCLUSIONS: No significant differences were observed in clinical status or overall mortality between patients treated with convalescent plasma and those who received placebo. (PlasmAr ClinicalTrials.gov number, NCT04383535.).

Influencia de las características clínicas y el hemograma basal del paciente en la composición final del plasma rico en plaquetas / Clinical characteristics of basal blood count with the final composition of platelet-rich plasma

Introducción: El objetivo del siguiente estudio fue evaluar la influencia de la edad, el sexo, el índice de masa corporal y el hemograma previo de los pacientes en la composición final del PRP. Materiales y métodos: Se realizó un análisis multivariado en trescientos pacientes para determinar la relación entre las mencionadas variables. Resultados: el número de plaquetas finales mostró una relación directa con las plaquetas basales (F (9.187) = 2.067, p = 0.034). Cuando las plaquetas basales aumentaron en una unidad, las plaquetas finales aumentan en promedio con un intervalo de valores de 0.236 a 4.618 (IC 95%, p = 0.00752). Discusión: el valor esperado medio de leucocitos para el protocolo "bajo" es de 1597 y para el nivel "rico" es de 9253, con un IC 95% se espera que el protocolo "rico" aumente en promedio la cantidad de leucocitos finales entre 280 y 785 % con respecto al protocolo "bajo" (p <0.001). Ninguna de las otras variables estudiadas tuvo una influencia significativa en la composición final del PRP. Conclusión: la cantidad de plaquetas en el hemograma basal afectó significativamente la concentración final de plaquetas en el PRP. Además, el protocolo de preparación afectó la concentración final de leucocitos, la que fue significativamente mayor en el protocolo de PRP rico en leucocitos que en el protocolo pobre en leucocitos. El sexo, el IMC y el HTO previo no influyeron significativamente en las concentraciones finales de plaquetas ni de leucocitos del PRP final. Nivel de Evidencia: IV

Introduction: The purpose of this study study was to evaluate the influence of age, sex, body mass index and previous blood count of patients on the final composition of the PRP. Material and methods: a multivariate analysis was performed in three hundred patients to determine the relationship between sex, age, body mass index (BMI) and the characteristics of the baseline blood count with the final composition of the PRP. Results: the number of final platelets showed a direct relationship with the basal platelets (F (9.187) = 2.067, p = 0.034). When the basal platelets increased by one unit, the final platelets increased on average with a range of values from 0.236 to 4.618 (95% CI, p = 0.00752).Discussion: the mean expected value of leukocytes for the "low" protocol is 1597 and for the "rich" level it was 9253, with a 95% CI the "rich" protocol is expected to increase on average the amount of final leukocytes between 280 and 785 % with respect to the "low" protocol (p <0.001). None of the other variables studied had a significant influence on the final composition of the PRP. Conclusion: the amount of platelets in the basal blood count significantly affected the final concentration of platelets in the PRP. Likewise, the preparation protocol affected the final leukocyte concentration, being the same significantly higher in the leukocyte-rich PRP protocol than in the leukocyte-poor protocol. Sex, BMI and previous HTO did not significantly influence the final platelet or leukocyte concentrations of the final PRP. Level of Evidence: IV

Antibody-induced crosslinking and cholesterol-sensitive, anomalous diffusion of nicotinic acetylcholine receptors.

Synaptic strength depends on the number of cell-surface neurotransmitter receptors in dynamic equilibrium with intracellular pools. Dysregulation of this homeostatic balance occurs, for example in myasthenia gravis, an autoimmune disease characterized by a decrease in the number of postsynaptic nicotinic acetylcholine receptors (nAChRs). Monoclonal antibody mAb35 mimics this effect. Here we use STORM nanoscopy to characterize the individual and ensemble dynamics of monoclonal antibody-crosslinked receptors in the clonal cell line CHO-K1/A5, which robustly expresses adult muscle-type nAChRs. Antibody labeling of live cells results in 80% receptor immobilization. The remaining mobile fraction exhibits a heterogeneous combination of Brownian and anomalous diffusion. Single-molecule trajectories exhibit a two-state switching behavior between free Brownian walks and anticorrelated walks within confinement areas. The latter act as permeable fences (~34 nm radius, ~400 ms lifetime). Dynamic clustering, trapping, and immobilization also occur in larger nanocluster zones (120-180 nm radius) with longer lifetimes (11 ± 1 s), in a strongly cholesterol-sensitive manner. Cholesterol depletion increases the size of the clustering phenomenon; cholesterol enrichment has the opposite effect. The disclosed high proportion of monoclonal antibody-crosslinked immobile receptors, together with their anomalous, cholesterol-sensitive diffusion and clustering, provides new insights into the antibody-enhanced antigenic modulation that leads to physiopathological internalization and degradation of receptors in myasthenia.

Cholesterol modulates acetylcholine receptor diffusion by tuning confinement sojourns and nanocluster stability.

Translational motion of neurotransmitter receptors is key for determining receptor number at the synapse and hence, synaptic efficacy. We combine live-cell STORM superresolution microscopy of nicotinic acetylcholine receptor (nAChR) with single-particle tracking, mean-squared displacement (MSD), turning angle, ergodicity, and clustering analyses to characterize the lateral motion of individual molecules and their collective behaviour. nAChR diffusion is highly heterogeneous: subdiffusive, Brownian and, less frequently, superdiffusive. At the single-track level, free walks are transiently interrupted by ms-long confinement sojourns occurring in nanodomains of ~36 nm radius. Cholesterol modulates the time and the area spent in confinement. Turning angle analysis reveals anticorrelated steps with time-lag dependence, in good agreement with the permeable fence model. At the ensemble level, nanocluster assembly occurs in second-long bursts separated by periods of cluster disassembly. Thus, millisecond-long confinement sojourns and second-long reversible nanoclustering with similar cholesterol sensitivities affect all trajectories; the proportion of the two regimes determines the resulting macroscopic motional mode and breadth of heterogeneity in the ensemble population.