[Early effectiveness of local injection of multimodal drug cocktail during anterior cruciate ligament reconstruction and its influence on cartilage].

Objective: To explore the early effectiveness and influence on cartilage of local injection of multimodal drug cocktail (MDC) during anterior cruciate ligament reconstruction (ACLR). Methods: Between February 2022 and August 2023, patients undergone arthroscopic ACLR using autologous hamstring tendons were selected as the study subjects. Among them, 90 patients met the selection criteria and were randomly divided into 3 groups ( n=30) according to the different injection drugs after ligament reconstruction. There was no significant difference in baseline data such as gender, age, body mass index, surgical side, disease duration, preoperative thigh circumference, and preoperative levels of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), IL-1, matrix metalloproteinase 3 (MMP-3), MMP-13, and aggrecan (ACAN) in synovial fluid between groups ( P>0.05). After the ligament reconstruction during operation, corresponding MDC (consisting of ropivacaine, tranexamic acid, and betamethasone in group A, and ropivacaine, betamethasone, and saline in group B) or saline (group C) were injected into the joint and tendon site, respectively. The length of hospital stay, postoperative tramadol injection volume, incidence of complications, degree of knee joint swelling and range of motion, visual analogue scale (VAS) score, International Knee Documentation Committee (IKDC) score, Lyshlom score, and Hospital for Special Surgery (HSS) score were recorded and compared between groups. The T2 * values in different cartilage regions were detected by MRI examination and the levels of TNF-α, IL-6, IL-1, MMP-3, MMP-13, and ACAN in synovial fluid were detected by ELISA method. Results: The patients in group A, B, and C were followed up (12.53±3.24), (13.14±2.87), and (12.82±3.32) months, respectively. All incisions healed by first intention. Compared with group C, group A and group B had shorter length of hospital stay, less tramadol injection volume, and lower incidence of complications, showing significant differences ( P<0.05); there was no significant difference between group A and group B ( P>0.05). The degree of knee swelling in group A was significantly less than that in group B and group C ( P<0.05), but there was no significant difference between group B and group C ( P>0.05). At 3, 6, 12, 24, and 48 hours after operation, VAS scores of group A and group B were significantly lower than those of group C ( P<0.05); at 72 hours after operation, there was no significant difference among the three groups ( P>0.05). At 3 days, 14 days, and 1 month after operation, the range of motion of knee joint in group A were significantly better than those in group C ( P<0.05), and there was no significant difference between the other groups ( P>0.05). At 1 month after operation, the IKDC score of group A and group B was significantly higher than that of group C ( P<0.05); there was no significant difference among the three groups at other time points ( P>0.05). There was no significant difference in Lyshlom score and HSS score among the three groups at each time point ( P>0.05). At 14 days after operation, the levels of IL-1 and IL-6 in the synovial fluid in groups A and B were significantly lower than those in group C ( P<0.05). There was no significant difference in the levels of TNF-α, MMP-3, MMP-13, and ACAN between groups A and B ( P>0.05). At 1 month after operation, there was no significant difference in the above indicators among the three groups ( P>0.05). At 3, 6, and 12 months after operation, there was no significant difference in the T2 * values of different cartilage regions among the three groups ( P>0.05). Conclusion: Injecting MDC (ropivacaine, tranexamic acid, betamethasone) into the joint and tendon site during ACLR can achieve good early effectiveness without significant impact on cartilage.

Neurodevelopmental Outcomes After Late Preterm Antenatal Corticosteroids: The ALPS Follow-Up Study.

Importance: The Antenatal Late Preterm Steroids (ALPS) trial changed clinical practice in the United States by finding that antenatal betamethasone at 34 to 36 weeks decreased short-term neonatal respiratory morbidity. However, the trial also found increased risk of neonatal hypoglycemia after betamethasone. This follow-up study focused on long-term neurodevelopmental outcomes after late preterm steroids. Objective: To evaluate whether administration of late preterm (34-36 completed weeks) corticosteroids affected childhood neurodevelopmental outcomes. Design, Setting, and Participants: Prospective follow-up study of children aged 6 years or older whose birthing parent had enrolled in the multicenter randomized clinical trial, conducted at 13 centers that participated in the Maternal-Fetal Medicine Units (MFMU) Network cycle from 2011-2016. Follow-up was from 2017-2022. Exposure: Twelve milligrams of intramuscular betamethasone administered twice 24 hours apart. Main Outcome and Measures: The primary outcome of this follow-up study was a General Conceptual Ability score less than 85 (-1 SD) on the Differential Ability Scales, 2nd Edition (DAS-II). Secondary outcomes included the Gross Motor Function Classification System level and Social Responsiveness Scale and Child Behavior Checklist scores. Multivariable analyses adjusted for prespecified variables known to be associated with the primary outcome. Sensitivity analyses used inverse probability weighting and also modeled the outcome for those lost to follow-up. Results: Of 2831 children, 1026 enrolled and 949 (479 betamethasone, 470 placebo) completed the DAS-II at a median age of 7 years (IQR, 6.6-7.6 years). Maternal, neonatal, and childhood characteristics were similar between groups except that neonatal hypoglycemia was more common in the betamethasone group. There were no differences in the primary outcome, a general conceptual ability score less than 85, which occurred in 82 (17.1%) of the betamethasone vs 87 (18.5%) of the placebo group (adjusted relative risk, 0.94; 95% CI, 0.73-1.22). No differences in secondary outcomes were observed. Sensitivity analyses using inverse probability weighting or assigning outcomes to children lost to follow-up also found no differences between groups. Conclusion and Relevance: In this follow-up study of a randomized clinical trial, administration of antenatal corticosteroids to persons at risk of late preterm delivery, originally shown to improve short-term neonatal respiratory outcomes but with an increased rate of hypoglycemia, was not associated with adverse childhood neurodevelopmental outcomes at age 6 years or older.

Comparison of side effects of different steroids used in intratympanic injections.

OBJECTIVES: This study aimed to compare the side effects of different steroids used in the intratympanic injections (IT). METHODS: One hundred and sixty patients diagnosed with sudden sensorineural hearing loss and undergoing IT were assigned to four groups based on the type or concentration of steroids administered (Group DM5: 5 mg/ml Dexamethasone sodium phosphate; Group DM10: 10 mg/ml Dexamethasone sodium phosphate; Group MP: 40 mg/ml Methylprednisolone sodium succinate; Group BM: 4 mg/ml Betamethasone sodium phosphate). Each group comprised 40 patients, and all participants received IT six times. The study assessed and compared the degrees and duration of pain, dizziness, and tympanic membrane damage following IT. Patients were asked to report the pain they felt using the numeric rating scale (NRS). RESULTS: NRS scores for pain after IT showed significant differences among the four groups (p < 0.001). The average NRS scores for pain in each group were as follows: Group DM5: 1.53 ± 1.04; Group DM10: 1.45 ± 1.30; Group MP: 4.33 ± 2.22; Group BM: 6.03 ± 1.46. The durations of pain after IT also exhibited significant differences among the four groups (p < 0.001), with the longest duration observed in Group MP at 31.93 ± 15.20 min. CONCLUSION: Different types of steroids could lead to varying degrees of pain when used in IT. Betamethasone could cause the most severe pain, and methylprednisolone could result in the longest duration of pain.

Effect of Perineural or Intravenous Betamethasone on Femoral Nerve Block Outcomes in Knee Arthroplasty: A Randomized, Controlled Study.

OBJECTIVES: Despite the use of multimodal analgesia, patients undergoing knee arthroplasty still encounter residual moderate pain. The addition of betamethasone to local anesthetic has been shown to improve postoperative pain. However, it remains uncertain whether the positive effects of perineural or intravenous administration of betamethasone on analgesia outcomes lead to better early mobility and postoperative recovery. METHODS: Between June 2022 and February 2023, a total of 159 patients who were undergoing knee arthroplasty were included in this study. These patients were allocated randomly into three groups: (i) the NS group, received ropivacaine 0.375% and intravenous 3mL 0.9% normal saline; (ii) the PNB group, received ropivacaine 0.375% plus perineural betamethasone (12mg) 3mL and intravenous 3mL 0.9% normal saline; and (iii) the IVB group, received ropivacaine 0.375% and intravenous betamethasone (12mg) 3mL. RESULTS: Both perineural and intravenous administration of betamethasone led to improved median (IQR) numeric rating scale (NRS) scores on the 6-meter walk test, with a score of 1.0 (1.0-2.0) for both groups, compared with 2.0 (1.0-2.0) for the NS group (p = 0.003). Compared to the NS group, both the PNB and IVB groups showed significant reductions in NRS scores at 24 and 36 h after surgery, along with a significant increase in ROM at 24, 36, and 48 h post-operation. Additionally, it exhibited lower levels of cytokine IL-1ß and TNF-α in fluid samples, as well as lower level of HS-CRP in blood samples in the PNB and IVB groups compared to the NS group. CONCLUSION: The administration of perineural and intravenous betamethasone demonstrated an enhanced analgesic effect following knee arthroplasty. Furthermore, it was associated with reduced levels of IL-1ß, TNF-α, and HS-CRP, as well as enhanced knee ROM, which is conducive to early ambulation and postoperative rehabilitation after knee arthroplasty.

Topical Betamethasone Treatment of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis with Ocular Involvement in the Acute Phase.

PURPOSE: To clarify the importance of administering topical steroids for the treatment of Stevens-Johnson syndrome (SJS) / toxic epidermal necrolysis (TEN) with ocular involvement in the acute phase. DESIGN: Retrospective case series. METHODS: Using the medical records of acute SJS/TEN patients treated at the Kyoto Prefectural University of Medicine Hospital, Kyoto, Japan, between July 2006 and July 2017, the ocular findings, topical steroid dosage, systemic steroid dosage, and ocular sequelae were retrospectively examined. The level of cytokines in tear fluid and serum samples was also analyzed. RESULTS: This study involved 13 cases. In 10 cases in whom the clinical courses were recorded before the start of steroid therapy, the mean acute ocular severity score (AOSS: 3 = very severe; 2 = severe; 1 = mild; 0 = none) was 2.8 ± 0.4 points in the severest phase. The mean systemic steroid dose after steroid pulse therapy was 694 ± 386 mg and the mean topical steroid (0.1% betamethasone eye drop and ointment) dose was 13.4 ± 3.3 times daily in the severest phase. Analysis of cytokine levels of 4 cases showed that a cytokine storm occurred in the tear fluid after the steroid pulse therapy. At final follow-up, 16 eyes of 8 patients had a logMAR visual acuity of ≤0, and no serious ocular sequelae were observed. CONCLUSIONS: In patients with SJS/TEN, ocular surface inflammation remains strong even after systemic inflammation has improved post steroid pulse therapy, thus suggesting that both systemic and topical steroid therapy should be administered appropriately.

Differences in thyroid function tests after administration of a single supraphysiological dose of ACTH or a high dose of a synthetic steroid.

OBJECTIVE: Although the suppressive action of synthetic steroids on the hypothalamus-pituitary-thyroid (HPT) axis is established, little is known regarding the effect of the administration of synthetic adrenocorticotropic hormone (ACTH). DESIGN: In the context of a randomized, open label, comparative study assessing the efficacy and safety of ACTH and betamethasone in the treatment of hospitalized patients with acute gout, we compared the effects of these agents on thyroid function tests. METHODS: Serum TSH, total T4 and T3 and cortisol were measured before and at 24 and 48 h after a single intramuscular dose of synthetic ACTH (1 mg) or betamethasone (6 mg), in 38 hospitalized patients with acute gout and normal thyroid function. RESULTS: The final analysis included 32 patients, due to missing data. The ACTH and betamethasone groups did not differ regarding the mean age, gender, severity of gout attack, and baseline thyroid parameters. In the ACTH group TSH and T4 were significantly decreased at 24 and at 48 h compared to baseline, while T3 was decreased at 24 but not at 48 h. In the betamethasone group T3 remained stable; TSH and T4 decreased significantly from baseline levels at 24 h; at 48 h, TSH had returned to and T4 showed a partial rebound towards pre-treatment values. CONCLUSIONS: A single IM administration of 1 mg of synthetic ACTH has more profound and prolonged effects on the HPT axis, lasting for at least 48 h, compared to a single IM dose of 6 mg betamethasone.

Maternal and infant morbidity following administration of repeat dexamethasone or betamethasone prior to preterm birth: A secondary analysis of the ASTEROID Trial.

BACKGROUND: Clinical practice guidelines recommend administering antenatal corticosteroids (ACS), either betamethasone or dexamethasone, to women at risk of preterm birth at less than 35 weeks' gestation. If women remain at risk of preterm birth seven or more days after an initial course of ACS, most guidelines recommend administration of a repeat dose(s). No randomised trials have assessed the efficacy of dexamethasone as a repeat steroid compared to betamethasone. AIM: We aimed to determine if there were differences between the use of dexamethasone or betamethasone as repeat ACS, for women who remain at risk of preterm birth after an initial course, on maternal, infant, and childhood health outcomes. METHODS: We performed a secondary analysis of data from the ASTEROID randomised trial, where women at risk of preterm birth were allocated to either betamethasone or dexamethasone. Infant, childhood, and maternal outcomes were compared according to whether women received a repeat dose(s) of dexamethasone or betamethasone. The primary outcome was a composite outcome of death or any neurosensory disability at age two years (corrected for prematurity). The ASTEROID trial is registered with ANZCTR, ACTRN12608000631303. RESULTS: 168 women and their infants were included, with 86 women receiving dexamethasone and 82 women receiving betamethasone as a repeat dose. Women in the two ACS groups had similar baseline characteristics. We observed little to no difference in the incidence of death or any neurosensory disability at age two years (OR 0.89, 95% CI 0.39 to 2.06, p = 0.79) or in the incidence of other infant, childhood, and maternal adverse health outcomes between women who received dexamethasone and those who received betamethasone. CONCLUSION: Use of dexamethasone for a repeat dose(s) compared to betamethasone did not result in any differences in infant, childhood, and maternal health outcomes. These results can be used to support clinical practice guideline recommendations.

Using in vitro ADME data for lead compound selection: An emphasis on PAMPA pH 5 permeability and oral bioavailability.

Membrane permeability plays an important role in oral drug absorption. Caco-2 and Madin-Darby Canine Kidney (MDCK) cell culture systems have been widely used for assessing intestinal permeability. Since most drugs are absorbed passively, Parallel Artificial Membrane Permeability Assay (PAMPA) has gained popularity as a low-cost and high-throughput method in early drug discovery when compared to high-cost, labor intensive cell-based assays. At the National Center for Advancing Translational Sciences (NCATS), PAMPA pH 5 is employed as one of the Tier I absorption, distribution, metabolism, and elimination (ADME) assays. In this study, we have developed a quantitative structure activity relationship (QSAR) model using our ∼6500 compound PAMPA pH 5 permeability dataset. Along with ensemble decision tree-based methods such as Random Forest and eXtreme Gradient Boosting, we employed deep neural network and a graph convolutional neural network to model PAMPA pH 5 permeability. The classification models trained on a balanced training set provided accuracies ranging from 71% to 78% on the external set. Of the four classifiers, the graph convolutional neural network that directly operates on molecular graphs offered the best classification performance. Additionally, an ∼85% correlation was obtained between PAMPA pH 5 permeability and in vivo oral bioavailability in mice and rats. These results suggest that data from this assay (experimental or predicted) can be used to rank-order compounds for preclinical in vivo testing with a high degree of confidence, reducing cost and attrition as well as accelerating the drug discovery process. Additionally, experimental data for 486 compounds (PubChem AID: 1645871) and the best models have been made publicly available (https://opendata.ncats.nih.gov/adme/).

Dosage escalation of antenatal steroids in preterm twin pregnancies does not improve long-term outcome.

OBJECTIVES: To analyze long-term effects of antenatal betamethasone (≤16 mg, =24 mg and >24 mg) in preterm twins on infant and childhood morbidity. METHODS: Retrospective cohort study among 198 preterm twins. Three follow up time points, including a total of 84 outcomes, were evaluated: first neonatal examination after birth and in the neonatal period up to 10 days after birth using data from the clinic charts; examination from the 21st to the 24th month of life and examination from the 60th to the 64th months, using data from copies of the children's examination booklets sent back by the parents. Dosage-dependent and sex-specific long-term effects of antenatal betamethasone treatment on neonatal, infant and early childhood development and morbidity up to 5.3 years of age were analyzed. RESULTS: Dosage escalation of >24 mg was not associated with improved neonatal, infant or early child hood outcome, independent of twin pair structure. In contrast, higher doses >24 mg were significantly linked to increased rates of congenital infections (OR 5.867, 95% CI 1.895-18.167). Male sex as a factor was obvious for lower rates of apnea-bradycardia-syndrome in neonates, higher rates of no free steps after 15 months in infancy and highest rates of motor clumsiness in early childhood. CONCLUSIONS: Betamethasone dosage escalation >24 mg in twins born between 23+5 and 33+6 weeks of gestation did not improve neonatal, infant or early childhood morbidity. In contrast, higher doses >24 mg total dose resulted in significantly higher rates of congenital infections and are not recommended. For males, 24 mg betamethasone appears to be the preferable dose.

Topical steroid containing combinations: Burden of adverse effects and why the recent regulatory action may not be enough.

OBJECTIVES AND METHODS: In September 2018, the government of India banned 328 fixed dose combinations (FDCs), 24 of which are combinations containing topical steroids. To assess what impact can be expected from this regulatory action, we analyzed reports of adverse drug events due to topical corticosteroids at a hospital-based pharmacovigilance center between January 2017 and August 2018. RESULTS: Among 34 different steroid-containing FDCs responsible for 485 reports of ADEs with topical steroids, only three preparations, accounting for 50.10% of ADEs, come under the umbrella of the recent ban. Clobetasone propionate (68.87%) and betamethasone (28.45%) were the corticosteroids most frequently associated with adverse events. Most of the steroid preparations (87.84%) had been bought without a prescription for the treatment of dermatophytoses (76.70%). Males (77.73%) were predominantly affected, and nearly half (47.43%) of the patients were between 21 and 30 years of age. Skin atrophy (50.10%), striae (25.54%), and hypopigmentation (19.79%) were the major ADEs. CONCLUSION: Nearly half of the cutaneous adverse effects were due to topical steroid combinations which are still widely available over the counter.

The effects of betamethasone on clinical outcome of the late preterm neonates born between 34 and 36 weeks of gestation.

BACKGROUND: Prenatal corticosteroid administration in preterm labor is one of the most important treatments available to improve neonatal outcomes; however, its beneficial effects on late preterm infants (after the 34th week of gestation) remained unknown. We aimed to assess the effects of betamethasone on the clinical condition of the late preterm infants born between 34 and 36 weeks of gestation. METHODS: This retrospective cohort study was performed on 100 consecutive infants born between 34 and 36 weeks of gestation and received betamethasone before delivery as the cases and 100 neonates with the same delivery conditions but without receiving betamethasone. All neonates were followed up within hospitalization to assess the neonatal outcome. RESULTS: The neonates receiving betamethasone suffered more from respiratory distress syndrome (49% versus 31%, p = 0.008, RR = 1.59 95% CI (1.12-2.27)) and requiring more respiratory support (71% versus 50%, p = 0.002, RR = 1.43 95% CI (1.13-1.80)) as compared to the control group. There was no difference between the two groups in other neonatal adverse events or death. CONCLUSION: the use of betamethasone in the late preterm period (after 34 weeks of gestation) has no beneficial effects on lung maturity or preventing neonatal adverse outcomes, even may lead to increase the risk for RDS and requiring respiratory support.

Antenatal Betamethasone Induces Increased Surfactant Proteins and Decreased Foxm1 Expressions in Fetal Rabbit Pups.

Introduction: Antenatal steroid improves respiratory distress syndrome in preterm infants. The molecular mechanism of the process is not well established. The aim of this study is to investigate the possible association between antenatal steroid and fetal Forkhead box M1(Foxm1) expression. Materials and methods: An animal study using mated pregnant New Zealand white rabbits and their fetuses was designed. Fourteen mother rabbits were assigned to four groups to undergo a cesarean section. In groups 1, 2, and 3, preterm pups were harvested on day 27 of gestation. In group 4, term pups were harvested on day 31. Antenatal maternal intramuscular injection was performed in groups 2 (normal saline) and 3 (betamethasone). Using qRT-PCR and Western blot, mRNA transcription and protein expression of surfactant protein (SP) A, B, C, and Foxm1 were compared between the pups of those four groups. Results: Sixty two fetal rabbits were harvested. One-way ANOVA test showed higher mRNA transcription of SPs in groups 3 and 4 than groups 1 and 2. Significantly lower Foxm1 mRNA transcription and protein expression were observed in group 3 or 4 compared with group 1 or 2. Conclusion: Decreased Foxm1 expression was associated in an antenatal betamethasone animal model.

Betamethasone administration during pregnancy is associated with placental epigenetic changes with implications for inflammation.

BACKGROUND: Glucocorticoids (GCs) play a pivotal role in fetal programming. Antenatal treatment with synthetic GCs (sGCs) in individuals in danger of preterm labor is common practice. Adverse short- and long-term effects of antenatal sGCs have been reported, but their effects on placental epigenetic characteristics have never been systematically studied in humans. RESULTS: We tested the association between exposure to the sGC betamethasone (BET) and placental DNA methylation (DNAm) in 52 exposed cases and 84 gestational-age-matched controls. We fine-mapped associated loci using targeted bisulfite sequencing. The association of placental DNAm with gene expression and co-expression analysis on implicated genes was performed in an independent cohort including 494 placentas. Exposure to BET was significantly associated with lower placenta DNAm at an enhancer of FKBP5. FKBP5 (FK506-binding protein 51) is a co-chaperone that modulates glucocorticoid receptor activity. Lower DNAm at this enhancer site was associated with higher expression of FKBP5 and a co-expressed gene module. This module is enriched for genes associated with preeclampsia and involved in inflammation and immune response. CONCLUSIONS: Our findings suggest that BET exposure during pregnancy associates with few but lasting changes in placental DNAm and may promote a gene expression profile associated with placental dysfunction and increased inflammation. This may represent a pathway mediating GC-associated negative long-term consequences and health outcomes in offspring.

Estimating fetal exposure to the P-gp substrates, corticosteroids, by PBPK modeling to inform prevention of neonatal respiratory distress syndrome.

We have previously developed a maternal-fetal physiologically-based pharmacokinetic (m-f PBPK) model to dynamically predict (and verify) fetal-maternal exposure to drugs that passively diffuse across the placenta. Here, we extended the application of this model to dynamically predict fetal exposure to drugs which are effluxed by placental P-glycoprotein, namely the antenatal corticosteroids (ACS; dexamethasone [DEX], and betamethasone [BET]). To do so, we estimated both the placental P-gp mediated efflux clearance (CL) and the passive diffusion CL of the ACS. The efficacy and toxicity of the currently used maternal ACS dosing regimens to prevent neonatal respiratory distress syndrome could be improved by altering their dosing regimens. Therefore, to illustrate the utility of our m-f PBPK model, we used it to design alternative dosing regimens of DEX and BET that could potentially improve their efficacy and reduce their toxicity. The redesigned dosing regimens are convenient to administer, maintain maternal-fetal exposure (area under the concentration-time curve [AUC]) or maximum plasma concentration (Cmax ) or both (DEX and BET) or minimize maternal exposure while maintaining fetal drug plasma concentrations above the minimum therapeutic threshold of 1 ng/ml for 48 h (BET only; based on efficacy data in sheep). To our knowledge, this is the first study to dynamically predict fetal plasma concentrations of placental P-gp effluxed drugs. Our approach and our m-f PBPK model could be used in the future to predict maternal-fetal exposure to any drug and to design alternative dosing regimens of the drug.

Interventions for the treatment of persistent post-COVID-19 olfactory dysfunction.

BACKGROUND: Olfactory dysfunction is an early and sensitive marker of COVID-19 infection. Although self-limiting in the majority of cases, when hyposmia or anosmia persists it can have a profound effect on quality of life. Little guidance exists on the treatment of post-COVID-19 olfactory dysfunction, however several strategies have been proposed from the evidence relating to the treatment of post-viral anosmia (such as medication or olfactory training). OBJECTIVES: To assess the effects (benefits and harms) of interventions that have been used, or proposed, to treat persisting olfactory dysfunction due to COVID-19 infection. A secondary objective is to keep the evidence up-to-date, using a living systematic review approach.  SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane COVID-19 Study Register; Cochrane ENT Register; CENTRAL; Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished studies. The date of the search was 16 December 2020. SELECTION CRITERIA: Randomised controlled trials including participants who had symptoms of olfactory disturbance following COVID-19 infection. Only individuals who had symptoms for at least four weeks were included in this review. Studies compared any intervention with no treatment or placebo. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Primary outcomes were the recovery of sense of smell, disease-related quality of life and serious adverse effects. Secondary outcomes were the change in sense of smell, general quality of life, prevalence of parosmia and other adverse effects (including nosebleeds/bloody discharge). We used GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS: We included one study with 18 participants, which compared the use of a 15-day course of oral steroids combined with nasal irrigation (consisting of an intranasal steroid/mucolytic/decongestant solution) with no intervention. Psychophysical testing was used to assess olfactory function at baseline, 20 and 40 days. Systemic corticosteroids plus intranasal steroid/mucolytic/decongestant compared to no intervention Recovery of sense of smell was assessed after 40 days (25 days after cessation of treatment) using the Connecticut Chemosensory Clinical Research Center (CCCRC) score. This tool has a range of 0 to 100, and a score of ≥ 90 represents normal olfactory function. The evidence is very uncertain about the effect of this intervention on recovery of the sense of smell at one to three months (5/9 participants in the intervention group scored ≥ 90 compared to 0/9 in the control group; risk ratio (RR) 11.00, 95% confidence interval (CI) 0.70 to 173.66; 1 study; 18 participants; very low-certainty evidence). Change in sense of smell was assessed using the CCCRC score at 40 days. This study reported an improvement in sense of smell in the intervention group from baseline (median improvement in CCCRC score 60, interquartile range (IQR) 40) compared to the control group (median improvement in CCCRC score 30, IQR 25) (1 study; 18 participants; very low-certainty evidence). Serious adverse events andother adverse events were not identified in any participants of this study; however, it is unclear how these outcomes were assessed and recorded (1 study; 18 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: There is very limited evidence available on the efficacy and harms of treatments for persistent olfactory dysfunction following COVID-19 infection. However, we have identified other ongoing trials in this area. As this is a living systematic review we will update the data regularly, as new results become available. For this (first) version of the living review we identified only one study with a small sample size, which assessed systemic steroids and nasal irrigation (intranasal steroid/mucolytic/decongestant). However, the evidence regarding the benefits and harms from this intervention to treat persistent post-COVID-19 olfactory dysfunction is very uncertain.

Synthesis and Evaluation of AlgNa-g-Poly(QCL-co-HEMA) Hydrogels as Platform for Chondrocyte Proliferation and Controlled Release of Betamethasone.

Hydrogels obtained from combining different polymers are an interesting strategy for developing controlled release system platforms and tissue engineering scaffolds. In this study, the applicability of sodium alginate-g-(QCL-co-HEMA) hydrogels for these biomedical applications was evaluated. Hydrogels were synthesized by free-radical polymerization using a different concentration of the components. The hydrogels were characterized by Fourier transform-infrared spectroscopy, scanning electron microscopy, and a swelling degree. Betamethasone release as well as the in vitro cytocompatibility with chondrocytes and fibroblast cells were also evaluated. Scanning electron microscopy confirmed the porous surface morphology of the hydrogels in all cases. The swelling percent was determined at a different pH and was observed to be pH-sensitive. The controlled release behavior of betamethasone from the matrices was investigated in PBS media (pH = 7.4) and the drug was released in a controlled manner for up to 8 h. Human chondrocytes and fibroblasts were cultured on the hydrogels. The MTS assay showed that almost all hydrogels are cytocompatibles and an increase of proliferation in both cell types after one week of incubation was observed by the Live/Dead® assay. These results demonstrate that these hydrogels are attractive materials for pharmaceutical and biomedical applications due to their characteristics, their release kinetics, and biocompatibility.

Ultrasound-Guided Transforaminal Injections of Platelet-Rich Plasma Compared with Steroid in Lumbar Disc Herniation: A Prospective, Randomized, Controlled Study.

Transforaminal steroid injection is extensively used as a treatment in cases of herniated disc, but it is associated with complications. In comparison, platelet-rich plasma (PRP) injection has been used in musculoskeletal disorders and could be another option. This study is aimed at comparing the efficacy and safety aspects between ultrasound-guided transforaminal injections of PRP and steroid in patients who suffer from radicular pain due to lumbar disc herniation. In a randomized controlled trial, ultrasound-guided transforaminal injections of either PRP (n = 61) or steroid (n = 63) were administered to a total of 124 patients who suffer from radicular pain due to lumbar disc herniation. Patients were assessed by the visual analogue scale (VAS), pressure pain thresholds (PPTs), Oswestry disability index (ODI), and the physical function (PF) and bodily pain (BP) domains of the 36-item short form health survey (SF-36) before operation and 1 week, 1 month, 3 months, 6 months, and 12 months after operation. The rate and latency of F-wave were obtained before operation and 12 months postoperation. There was no statistical difference in terms of age and sex between both groups. Statistically significant improvements from the patients' data before operation to data obtained 1-month postoperation were observed in VAS, PPTs, ODI, and PF and BP of SF-36 in both groups and kept for 1 year. F-wave rate and latency were improved significantly at 1-year postoperation in both groups. Intergroup differences during follow-ups over a period of 1 year were not found to be significant in all the above assessment between the PRP and steroid groups. No complications were reported. The results showed similar outcome for both transforaminal injections using PRP and steroid in the treatment of lumbar disc herniation, suggesting the possible application of PRP injection as a safer alternative. The trial was registered in the Chinese Clinical Trial Registry (ChiCTR-INR-17011825).