Full Clearance Research Articles

Factors Associated with Loss to Follow-Up in Pediatric Concussion Patients after Initial Visit: A Retrospective Study at a Concussion Clinic

ObjectiveThe objective of this retrospective study is to identify factors associated with loss to follow-up for post-concussion clearance in pediatric patients by comparing loss to follow-up and full clearance patients. MethodsThis retrospective single-center cohort study analyzed 140 consecutive patients at a pediatric concussion clinic of a safety-net hospital for loss to follow-up, defined as not achieving clearance at last appointment. Univariate and multivariate regression models were fit on variables of interest, including demographic, mechanism and severity of concussion, and characteristics of the first evaluation post-concussion and follow-up management. ResultsOf the sample, 40% (n=56) achieved clearance and 60% (n=84) were lost to follow-up. Median age was 15 (IQR 11-17), with male predominance (60.7%). Living with a biological parent (OR =0.145, 95% CI =0.028-0.760) and sports involvement (OR =0.256, 95% CI =0.092-0.764) were protective factors, while being 10 years old or older (OR = 13.466, 95% CI = 2.792-64.958) and attending 2 or fewer follow-up appointments (OR = 19.027, 95% CI = 4.991-72.533) were risk factors for loss to follow-up. No significant differences were found between sex, race, driving distance, type of insurance, and mechanism of injury. ConclusionLiving with a biological parent and involvement in sports showed to be protective factors for loss to follow-up. Age at time of concussion and number of appointments were risk factors. A “golden window” of two appointments was identified, highlighting the need of a strong rapport and engagement in shared decision making. Future directions include prospective studies implementing strategies targeting adolescents and building a strong patient-provider relationship.

Missing School Days Following Sport-Related Concussion in High School Athletes

Sport-related concussions (SRC) can significantly impact students' attendance and academic performance, highlighting the importance of gradual return-to-learn protocols for recovery. Understanding the association between missed school days and recovery, especially across genders, is vital for effective concussion management in high school athletes. To describe missed school days in high school athletes with SRC and to determine associations between missed school days and authorized clearance to return to competition; secondarily, to determine whether school days missed differed by gender. Cohort study among student athletes participating in athletics sponsored by the Michigan High School Athletic Association (MHSAA) during academic years 2015 to 2023. SRC was a participant eligibility criterion and was defined as a head injury during participation in a MHSAA-sanctioned event. Data were analyzed from August 2015 to June 2023. Primary exposure was missed school days; additional exposures included gender, year of season, concussion history, event type, sport level, contact level, and athletic trainer involvement. The primary outcome was time to full unrestricted clearance following SRC. The analysis included a total of 20 934 individuals with SRC (13 869 boys [66.25%]). Gender (χ23 = 167.40; P < .001), season (χ221 = 57.41; P < .001), event type (χ23 = 99.29; P < .001), sport level (χ29 = 68.15; P < .001), contact level (χ26 = 56.73; P < .001), and initial evaluation (χ23 = 147.13; P < .001) were independently associated with missed school days. Athletes took a median (IQR) of 11 (7-16) days to return to full unrestricted clearance. Relative to no missed school days, there was a significant mean increase of 57% (incidence rate ratio, 1.57; 95% CI, 1.52-1.62) in time to full unrestricted clearance for 3 or more missed school days. The estimated mean days to return to sport were 12.15 (95% CI, 12.00-12.30) for 0 missed school days, 12.68 (95% CI, 12.39-12.96) for 1 missed school day, 15.47 (95% CI, 15.06-15.87) for 2 missed school days, and 19.08 (95% CI, 18.55-19.62) for 3 or more missed school days. This cohort study found that high school athletes typically missed 2 or fewer school days after SRC, suggesting that concussion management teams adhered to current recommendations of 24 to 48 hours of initial rest. The dose association, with more missed school days associated with slower return to play, suggests athletes' missing more school days (eg, ≥3) may be associated with severity of concussion and warrant additional support to return to school and/or sport.

Comparison of Clinical and Radiographic Outcomes Between Solid Headless and Headed Screws in the Treatment of Zone II and III Fifth Metatarsal Fractures in Elite Athletes

Background: Zone II and III fifth metatarsal (5-MT) fractures among athletes are typically managed with percutaneous fixation following anatomic reduction. However, screw head discomfort and refracture after bone union can occur because of the loads placed on the foot during play. Several hardware systems that use a smaller screw head compared to traditional hardware systems have been developed to minimize the rate of postoperative hardware complications. This study compares clinical and radiographic outcomes of 5-MT fractures in elite athletes treated with a solid headless screw vs a solid headed screw. We hypothesized that the headless screw would be associated with faster union rates, faster clearance times, and lower incidence of symptomatic hardware compared to the headed screw. Methods: Athletes competing at a collegiate level or higher treated for a zone II or III 5-MT fracture between 2016 and 2022 by 2 surgeons fellowship-trained in foot and ankle orthopaedics were screened. Operative notes were reviewed to determine the hardware system used. Subjects were divided based on the hardware system used during operation: headed screw and headless screw. Time to radiographic union, time to full clearance, and return to competition were determined. Postoperative complications, including nonunions, need for revision, need for hardware removal, and refractures were also noted. Results: Forty eligible patients (44 feet) were identified. The solid headed screw group included 20 patients (21 fractures), and the solid headless screw group included 20 patients (23 fractures). Average time to union for the headed screw group was 11.78 (range, 5.86-19.00) weeks; average time to union for the headless screw group was 11.65 (range, 6.00-22.57) weeks ( P = .93). Nineteen out of twenty (95%) patients were able to return to competition in both groups. Average time to return to competition for the headed screw group was 26.9 (range, 10.00-47.86) weeks, while average time for the headless screw group was 21.2 (range, 6.86-55.00) weeks ( P = .55). The overall complication rate for the headed screw was 23.8%, which was not statistically different from the overall complication rate for the headless screw of 13.0% ( P = .35). Conclusion: In this relatively small sample of elite athletes undergoing operative fixation of a 5-MT fracture, fixation using either a headless or headed screw system had similar good outcomes in regard to times to union, return to competition, and complication rate regardless of solid screw head type used. Level of Evidence: Level III, retrospective cohort study.

Modeling suggests SARS-CoV-2 rebound after nirmatrelvir-ritonavir treatment is driven by target cell preservation coupled with incomplete viral clearance.

In a subset of SARS-CoV-2 infected individuals treated with the oral antiviral nirmatrelvir-ritonavir, the virus rebounds following treatment. The mechanisms driving this rebound are not well understood. We used a mathematical model to describe the longitudinal viral load dynamics of 51 individuals treated with nirmatrelvir-ritonavir, 20 of whom rebounded. Target cell preservation, either by a robust innate immune response or initiation of nirmatrelvir-ritonavir near the time of symptom onset, coupled with incomplete viral clearance, appear to be the main factors leading to viral rebound. Moreover, the occurrence of viral rebound is likely influenced by time of treatment initiation relative to the progression of the infection, with earlier treatments leading to a higher chance of rebound. Finally, our model demonstrates that extending the course of nirmatrelvir-ritonavir treatment, in particular to a 10-day regimen, may greatly diminish the risk for rebound in people with mild-to-moderate COVID-19 and who are at high risk of progression to severe disease. Altogether, our results suggest that in some individuals, a standard 5-day course of nirmatrelvir-ritonavir starting around the time of symptom onset may not completely eliminate the virus. Thus, after treatment ends, the virus can rebound if an effective adaptive immune response has not fully developed. These findings on the role of target cell preservation and incomplete viral clearance also offer a possible explanation for viral rebounds following other antiviral treatments for SARS-CoV-2.

The influence of prior COVID-19 diagnosis on concussion recovery outcomes.

While the clinical presentations of COVID-19 and concussion are not identical, there is a significant overlap in symptomology (e.g., fatigue, headache) and neurological deficits (e.g., cognitive, vestibular). However, limited research has examined the effect of prior COVID-19 diagnosis on concussion outcomes. Therefore, the purpose of this study was to determine if prior diagnosis of COVID-19 influences concussion outcomes, including concussion assessment scores and recovery time, in college-aged individuals. A prospective study of college-aged individuals (COVID-19: n = 43, mean age 21.3 [SD 2.5] years; no COVID-19: n = 51, mean age 21.0 [SD 2.5] years) diagnosed with concussion was conducted. Demographics, injury details, the Sport Concussion Assessment Tool 5th Edition (SCAT5), and the Vestibular/Ocular Motor Screening (VOMS) were completed at the acute (within 5 days after concussion) and full medical clearance (FMC) (within 3 days after FMC) visits. Mann-Whitney U-tests determined differences in concussion outcomes between groups. Cox proportional hazards regression models were fitted to assess the relationship between factors associated with concussion symptom resolution and days to FMC, and covariates were selected based on previous literature indicating potential confounds (e.g., female sex, acute symptom severity, preexisting mental health conditions). Hazard ratios with 95% confidence intervals were reported for each predictor variable. No significant differences were found between groups for SCAT5 and VOMS composite and total scores. Significant differences were found between COVID-19 and no-COVID-19 groups in days to symptom resolution (11.5 days vs 8 days, p = 0.021), but not in days to FMC (14 days vs 12 days, p = 0.099). The association between COVID-19 groups and days to clearance was not significant when adjusting for sex, race, history of depression/anxiety, and total number of concussion symptoms at the acute visit [χ2(5) = 8.349, p = 0.138]. However, male sex (HR 2.036, 95% CI 1.033-4.014; p = 0.040) was associated with a quicker time to FMC. Prior COVID-19 diagnosis did not influence cognitive abilities and vestibular/ocular functioning as measured by the SCAT5 and VOMS postconcussion. While prior COVID-19 diagnosis did result in a significantly longer duration to symptom resolution when compared with individuals who did not have a prior COVID-19 diagnosis, prior COVID-19 did not significantly influence time to FMC by a healthcare provider. Clinicians should consider that individuals with a prior diagnosis of COVID-19 might experience prolonged symptoms postconcussion.

The association between continuing to play, clinical domains, and recovery outcomes in collegiate athletes following concussion.

Continued play following concussion can lead to worse outcomes and longer recoveries compared with athletes who immediately report. This has been well documented in youth athletes, while less attention has been paid to collegiate athletes despite differences in healthcare access, recovery trajectories, and additional pressures to play. Therefore, the purpose of this study was to determine if continuing to play immediately following a concussion influenced clinical outcomes and recovery time in collegiate athletes. A prospective, repeated-measures design was used to compare clinical outcomes and recovery time between collegiate athletes who continued playing (n = 37) and those immediately removed (n = 56) after a concussion. Assessments were conducted within 5 days of the concussion and at full medical clearance (FMC; ± 3 days) using the Sport Concussion Assessment Tool-5th edition (SCAT5), Vestibular/Ocular Motor Screening assessment, and High-Level Mobility Assessment Tool. Mann-Whitney U-tests determined differences in clinical outcomes between groups. Cox proportional hazards regression models examined the relationship between factors associated with days to symptom resolution and days to FMC, and covariates were selected a priori based on previous literature. Hazard ratios with 95% CIs were reported for each predictor variable. Significant differences were found in SCAT5 concentration composite scores (p = 0.010) and SCAT5 delayed recall composite scores (p = 0.045) at the acute visit and near point of convergence average distance (cm; p = 0.005) at the FMC visit between the group who continued to play and those who were immediately removed. There were no differences between groups in days to symptom resolution (10 vs 7 days, p = 0.05) and days to clearance (13 vs 11.50 days, p = 0.13). The association between groups and days to symptom resolution (χ2[4] = 5.052, p = 0.282), and days to clearance (χ2[4] = 3.624, p = 0.459) were not significant when adjusting for covariates. Collegiate athletes who continued to play following concussion did not exhibit worse clinical outcomes or recovery times compared with athletes who were immediately removed. While the lack of differences found in this study could be supported by prior literature, including improved education, awareness, reporting attitudes, and concussion management at the collegiate level in recent years, the authors believe discrepancies are more likely due to study-specific differences (e.g., sample size, care setting, and timing). Therefore, these findings should not diminish the dangers of continued play and the importance of timely removal after concussion.

Can TTMV clearance predict recurrence in HPV HNSCC?

6066 Background: Patients with locally advanced (LA) HPV HNSCC are treated with various types of induction chemotherapy (IC) followed by standard (sd) or reduced (rd) chemoradiation (CRT). Tumor tissue-modified viral HPV DNA (TTMV) pairs with PET-CT in predicting an early detection of treatment failure in HPV-related HNSCC. Mid-treatment TTMV assessment in HPV-related HNSCC can help identify patients who are eligible to receive a lower dose of IC and/or CRT or those who may require close follow-up. Methods: Patients with LA HPV+ HNSCC with high-risk features (radiographic ECE, T4 primary, &gt;N2c) and &lt;20 pack-year (py) smoking history were treated with IC followed by rdCRT (56 Gy); sdCRT (70 Gy) was used in non-responders. 16/23 received IC with TPF, 1/23 TP, and 6/23 TP-PD1, and all patients received carboplatin weekly with their CRT. Regeneron trial patients who received TP-Cemiplimab (PD1) IC followed by sdCRT are also continuing adjuvant Cemiplimab alone for 6 months (NCT05376553). PET-CT-confirmed residual, recurrent, or metastatic diseases were defined as treatment failures; TTMV + patients only if PET-CT confirmed. Results: 23 subjects treated with IC followed by CRT between 2/4/21-1/26/24, who had pre- and post-treatment TTMV were included in our analysis. The median pre-IC TTMV was 8082 (27 – 90770). The median follow-up time from treatment start was 21 months. 9/23 patients had full clearance TTMV after 1 cycle of IC defined as rapid responders (RR). 11/23 patients still had positive TTMV after 1st cycle of IC were defined as slow responders (SR). 1 patient had no TTMV done after 1 cycle of IC but was elevated after 2nd IC; he was defined as SR. 2 patients had a positive pre-IC TTMV, but no TTMV was drawn during IC to see if RR. 1 of 2 patients was TTMV negative prior to CRT, and 2/2 had a 1st post IC negative TTMV done 1 week after CRT started. They were both included in the analysis but defined as unknown response status. TTMV testing was done for all 23 subjects after CRT; all were negative. All subjects have TTMV testing done during their surveillance visits. Among 9/23 RR, none developed a failure. Among 12/23 SR, 3 patients developed a failure: 1/3 was TTMV+ but PET-, being followed with TTMV and PET-CT; and 2/3 were confirmed failures, TTMV+ and PET+; 1 locoregional, 1 metastatic. 2 patients were not known to be a SR or RR and had no recurrence. Among 23 patients, NPV of TTMV to detect failure was 100%, but PPV was 96% (1/23). Conclusions: IC followed in rapid clearance of TTMV in 39% of patients, and all remained disease-free. 3/11 (27%) with persistently elevated TTMV after cycle 1 relapsed as of this time point. This small study was not large enough to be practice-changing. However, this is significantly hypothesis-generating and should be tested in a larger trial to help identify patients for de-escalation (RR) or closer surveillance (SR).

Combination of Systemic and Lock-Therapies with Micafungin Eradicate Catheter-Based Biofilms and Infections Caused by Candida albicans and Candida parapsilosis in Neutropenic Rabbit Models.

Vascular catheter-related infections, primarily caused by Candida albicans and Candida parapsilosis, pose significant challenges due to the formation of biofilms on catheters, leading to refractory disease and considerable morbidity. We studied the efficacy of micafungin in systemic and lock therapies to eliminate catheter-based biofilms and deep tissue infections in experimental central venous catheter (CVC)-related candidemia in neutropenic rabbits. Silastic CVCs in rabbits were inoculated with 1 × 103 CFU/mL of C. albicans or C. parapsilosis, establishing catheter-based biofilm, and subjected to various treatments. Neutropenic rabbits treated with a combination of lock therapy and systemic micafungin demonstrated the most significant reduction in fungal burden, from 5.0 × 104 to 1.8 × 102 CFU/mL of C. albicans and from 5.9 × 104 to 2.7 × 102 CFU/mL of C. parapsilosis (p ≤ 0.001), in the CVC after 24 h, with full clearance of blood cultures after 72 h from treatment initiation. The combination of lock and systemic micafungin therapy achieved eradication of C. albicans from all studied tissues (0.0 ± 0.0 log CFU/g) vs. untreated controls (liver 7.5 ± 0.22, spleen 8.3 ± 0.25, kidney 8.6 ± 0.07, cerebrum 6.3 ± 0.31, vena cava 6.6 ± 0.29, and CVC wash 2.3 ± 0.68 log CFU/g) (p ≤ 0.001). Rabbits treated with a combination of lock and systemic micafungin therapy demonstrated a ≥2 log reduction in C. parapsilosis in all treated tissues (p ≤ 0.05) except kidney. Serum (1→3)-β-D-glucan levels demonstrated significant decreases in response to treatment. The study demonstrates that combining systemic and lock therapies with micafungin effectively eradicates catheter-based biofilms and infections caused by C. albicans or C. parapsilosis, particularly in persistently neutropenic conditions, offering promising implications for managing vascular catheter-related candidemia and providing clinical benefits in cases where catheter removal is not feasible.

Effects of fermented sweet potato residue on nutrient digestibility, meat quality, and intestinal microbes in broilers

This study aimed to investigate the effects of different proportions of dietary fermented sweet potato residue (FSPR) supplementation as a substitute for corn on the nutrient digestibility, meat quality, and intestinal microbes of yellow-feathered broilers. Experiment 1 (force-feeding) evaluated the nutrient composition and digestibility of mixtures with different proportions of sweet potato residue (70%, 80%, 90%, and 100%) before and after fermentation. In Experiment 2 (metabolic growth), a total of 420 one-day-old yellow-feathered broilers were randomly allocated to 4 groups and fed corn-soybean meal-based diets with 0, 5%, 8%, and 10% FSPR as a substitute for corn. The force-feeding and metabolic growth experiments were performed for 9 and 70 d, respectively. The treatment of 70% sweet potato residue (after fermentation) had the highest levels of crude protein, ether extract, and crude fiber and improved the digestibility of crude protein and amino acids (P < 0.05). Although dietary FSPR supplementation at different levels had no significant effect on growth performance and intestinal morphology, it improved slaughter rate, half-chamber rate, full clearance rate, and meat color, as well as reduced cooking loss in the breast and thigh muscles (P < 0.05). Dietary supplementation with 8% and 10% FSPR increased the serum immunoglobulin M and immunoglobulin G levels in broilers (P < 0.05). Furthermore, 10% FSPR increased the Shannon index and Ruminococcaceae_UCG-014, Ruminococcaceae_UCG-010 and Romboutsia abundances and decreased Sutterella and Megamonas abundances (P < 0.05). Spearman's correlation analysis showed that meat color was positively correlated with Ruminococcaceae_UCG-014 (P < 0.05) and negatively correlated with Megamonas (P < 0.05). Collectively, 70% sweet potato residue (after fermentation) had the best nutritional value and nutrient digestibility. Dietary supplementation with 8% to 10% FSPR as a substitute for corn can improve the slaughter performance, meat quality, and intestinal microbe profiles of broilers. Our findings suggest that FSPR has the potential to be used as a substitute for corn-soybean meals to improve the meat quality and intestinal health of broilers.

A mathematical model for the within-host (re)infection dynamics of SARS-CoV-2

Interactions between SARS-CoV-2 and the immune system during infection are complex. However, understanding the within-host SARS-CoV-2 dynamics is of enormous importance for clinical and public health outcomes. Current mathematical models focus on describing the within-host SARS-CoV-2 dynamics during the acute infection phase. Thereby they ignore important long-term post-acute infection effects. We present a mathematical model, which not only describes the SARS-CoV-2 infection dynamics during the acute infection phase, but extends current approaches by also recapitulating clinically observed long-term post-acute infection effects, such as the recovery of the number of susceptible epithelial cells to an initial pre-infection homeostatic level, a permanent and full clearance of the infection within the individual, immune waning, and the formation of long-term immune capacity levels after infection. Finally, we used our model and its description of the long-term post-acute infection dynamics to explore reinfection scenarios differentiating between distinct variant-specific properties of the reinfecting virus. Together, the model’s ability to describe not only the acute but also the long-term post-acute infection dynamics provides a more realistic description of key outcomes and allows for its application in clinical and public health scenarios.

The role of long-lived plasma cells in viral clearance

ABSTRACT The adaptive immune system has two types of plasma cells (PC), long-lived plasma cells (LLPC) and short-lived plasma cells (SLPC), that differ in their lifespan. In this paper, we propose that LLPC is crucial to the clearance of viral particles in addition to reducing the viral basic reproduction number in secondary infections. We use a sequence of within-host mathematical models to show that, CD8 T cells, SLPC and memory B cells cannot achieve full viral clearance, and the viral load will reach a low positive equilibrium level because of a continuous replenishment of target cells. However, the presence of LLPC is crucial for viral clearance.

The significance of clinically insignificant residual fragments after percutaneous nephrolithotomy: an analysis into the relevance of complete stone clearance

PurposeAfter treatment for kidney stones, residual fragments with a diameter of ≤ 4 mm are traditionally referred to as ‘clinically insignificant residual fragments’. We hypothesize that patients with these fragments are at an increased risk for stone-related morbidity, such as complaints, hydronephrosis, and stone regrowth, when compared to stone-free patients. This study aimed to investigate the relevance of complete stone clearance in surgical treatment of urolithiasis.MethodsWe conducted a single-center retrospective cohort study. Patients who underwent percutaneous nephrolithotomy between 2015 and 2020 were included if a CT-scan was available within 6 months after the procedure, and the follow-up duration was at least 1 year. The stone-free status at the end of the first stone episode during the study period was categorized as fully stone-free, not stone-free with small residual fragments (≤ 4 mm) and not stone-free with large residual fragments (> 4 mm). Follow-up data were collected, including stone-related events and re-intervention rates.ResultsA total of 103 subjects were included with a median follow-up of 21.4 months. Stone-related events occurred in 10 (29.4%) of the fully stone-free subjects, 20 (58.8%) of the subjects with small residual fragments and 25 (71.4%) of the subjects with large residual fragments. The stone-related event-free survival per subgroup resulted in a significantly different survival distribution in a log rank test (p = 0.008).ConclusionA complete stone-free status seems to be of fundamental importance for decreasing stone-related morbidity. Further developments and research should focus on optimizing the full clearance of stone material during PCNL.

Factors effecting the success of retrograde intrarenal surgery in pediatric patients with renal stones: The experience of two tertiary centres with 368 renal units

Currently, in the field of pediatric urology, the primary aim of surgical approaches for the treatment of renal stone disease is to provide a stoneless state through minimally invasive methods, and to prevent the damage that such stones may cause in the urinary system and stone recurrence. The aim of this study was to evaluate the efficacy and safety of RIRS and the factors affecting its success in the surgical treatment of renal stones in pediatric patients. Data from 357 pediatric and 368 renal units were collected retrospectively. The recorded parameters were age, gender, location and burden of the stone, and presence of postoperative residual stones. The stone location was the upper pole in 28 (7.6%) patients, the middle pole in 44 (12%), the pelvis in 98 (26.6%), the lower pole in 139 (37.8%), and multiple locations in 59 (16%) patients. A stoneless state was achieved in 277 (75.3%) units, while 91 units (24.7%) had residual stones at the end of the first month. In the multivariate analysis, the development of residual stones was found to be significantly associated with age (odds ratio [OR], 1.123; p=0.012) and stone location (OR, 3.142; p=0.018). RIRS is an endourological procedure with a high success rate in the achievement of a stoneless state in both pediatric and adult age groups, with an 82-100% success rate reported in various studies. A full stoneless state was achieved in 277 (75.3%) units after the initial RIRS in the present study, and full stone clearance was achieved in 304 units after the second RIRS session, with a success rate of 82.6%. A limitation of our study is that it was not performed by a single surgeon, and stone samples could not be taken from all patients for stone analysis. RIRS has also been associated with a high success rate in the endoscopic treatment of renal stones and is an efficient and safe method with a minimal rate of complications, especially in the pediatric age group.

IBC‐Ab002 Fc modifications for fast clearance are associated with advantageous safety profile

AbstractBackgroundImmune checkpoint inhibitors (ICI) have been suggested as a unique therapy for treating neurodegenerative diseases. IBC‐Ab002 is a novel fully human anti‐PD‐L1 monoclonal antibody developed by ImmunoBrain Checkpoint (IBC) for the treatment of Alzheimer’s disease (AD).In cancer patients, ICI treatments are often associated with immune‐related adverse events (irAEs), which are side effects that manifest as either temporary or permanent autoimmune conditions caused by drug administration. One example of such an event is T cell‐mediated pancreatic tissue damage leading to autoimmune diabetes. The management of irAE often involves treatment discontinuation until symptoms relief, which has unwanted impact on the effectiveness of therapies that depend on continuous drug exposure.Unlike common ICI used in oncology, PD‐L1 blockade mechanism of action in mouse models of neurodegenerative diseases was shown to be dependent on transient immune system stimulation. Accordingly, IBC‐Ab002 antibody was designed with modifications on its Fc backbone that shorten its circulation half‐life, to meet the pharmacokinetic and pharmacodynamic characteristics needed for treating AD.MethodSurrogate antibodies that block mouse PD‐L1 and share the same hIgG1 Fc‐modifications as IBC‐Ab002 were generated and tested for their propensity to accelerate the onset of autoimmune diabetes in NOD transgenic mice, which spontaneously develop type 1 diabetes. Mice were monitored for their blood‐glucose levels, weight, and survival – for both the acute and long‐term duration following antibody administration.ResultWe found that administration of a therapeutically effective dose of IBC‐Ab002’s surrogate antibody led to fewer cases of premature diabetes onset in NOD mice, when compared with an antibody variant that contains no Fc‐modifications. Furthermore, no excessive weight loss, change in the time‐course of spontaneous diabetes onset or early mortality, were found following IBC‐Ab002’s surrogate treatment, compared with isotype‐control treated mice, in a 200‐days follow‐up assessment.ConclusionWe demonstrate that the clearance rate of the antibody inversely‐relates to the probability of developing an adverse immune response, and that no delayed long‐term irAEs are expected once full clearance of the antibody was achieved. Overall, these findings suggest that shortening the half‐life of anti‐PD‐L1 antibodies in treatments that do not necessitate continuous exposure can considerably increase the safety profile.

Optimized selection of neodymium laser parameters for successful enlarged veins treatment.

Full clearance and no side effects method of treating enlarged veins was successfully accomplished by one laser session. This is the ambition and dream of both dermatologists and patients. Most vascularity treatment protocols had shown some unpleasant adverse effects. The purpose of the present work is to work out, in advance, the accurate dose of laser pulse duration and fluence in order to treat varicose veins in the face, arms and legs with no adverse effects. This mission required the calculation of the exact rise in temperature of the enlarged vein; prior to laser treatment. These pre-calculated temperature rise values were tested on 20 subjects in order to have the best clinical outcomes; using fundamental frequency (1064nm) pulsed Nd: YAG laser. This work necessitated the use of pulse length (15-30ms), spot size (3, 5mm), fluence (110-190J/cm2) and skin cooling temperature (3-18°C). Cooling of the skin before and after the treatment was needed to guarantee ultimate impactful results without side effects.

Changes in State and Trait Anxiety Throughout Concussion Recovery in High School- and College-Aged Individuals.

Researchers have indicated that individuals may experience anxiety symptoms after concussion. A potential mechanism for these presentations is shifts in anxiety throughout recovery. To examine the levels of state and trait anxiety in individuals after concussion throughout recovery compared with the levels in individuals serving as uninjured matched control participants. Prospective cohort study. University laboratory. Seventy-eight high school- and college-aged individuals (concussion group = 39, age = 18.4 ± 2.3 years; matched control group = 39, age = 18.4 ± 2.3 years) were enrolled. The State-Trait Anxiety Inventory was administered within 72 hours of injury (day 0: first test session), 5 days (±1 day) after the first test session (day 5), and at the time of full medical clearance (+2 days). Separate 2 × 3 repeated-measures analyses of variance were used to investigate differences in state and trait anxiety for each group throughout recovery. State and trait anxiety were higher in the concussion group than in the control group at day 0, day 5, and full medical clearance. For state anxiety, we observed a group × time interaction (F2,150 = 10.45, P < .001, ƞp2 = 0.12). For trait anxiety, we did not note an interaction (F1.74,150 = 1.5, P = .22, ƞp2 = 0.02) but did find main effects for time (F1.74,150 = 25.7, P < .001, ƞp2 = 0.3) and group (F1,75 = 7.23, P = .01, ƞp2 = 0.09). Participants with concussion experienced higher levels of state anxiety throughout recovery than matched control individuals. Although trait anxiety was higher in the concussion group and decreased over time, no interaction was seen, demonstrating that concussion may not affect this aspect of personality. Postinjury anxiety may result from increased state anxiety, and clinicians should screen for and manage these symptoms throughout recovery.

Balloon pulmonary angioplasty outcomes in patients previously treated by pulmonary endarterectomy surgery are inferior to those of inoperable patients

AbstractPulmonary endarterectomy (PEA) may not achieve full clearance of vascular obstructions in patients with more distal chronic thromboembolic pulmonary hypertension (CTEPH). Balloon pulmonary angioplasty (BPA) may be indicated to treat these residual vascular lesions. We compared whether patients post‐PEA (PP) treated by BPA derived similar benefit to those who had inoperable CTEPH (IC), and assessed predictors of BPA response after surgery. We treated 109 patients with BPA—89 with IC and 20 PP. Serial right heart catheterization performed at baseline (immediately before BPA) and 3 months after completing BPA, compared pulmonary vascular resistance (PVR), mean pulmonary artery pressure (mPAP) as well as change in WHO functional class and 6‐minute walk distance. We also assessed the impact of total thrombus tail length (TTTL) from photographed PEA surgical specimens and PP computed tomography pulmonary angiography (CTPA)‐quantified residual disease burden on BPA response. PP and IC groups did not differ significantly in terms of demographics, baseline hemodynamics or procedural characteristics. However, IC derived greater hemodynamic benefit from BPA: ΔPVR (−27.9 ± 20.2% vs. −13.9 ± 23.9%, p &lt; 0.05) and ΔmPAP (−17.1 ± 14.4% vs. −8.5 ± 18.0%, p &lt; 0.05). There was a negative correlation between pre‐BPA PVR and TTTL (r = −0.47, p &lt; 0.05) which persisted post‐BPA. PVR, mPAP, WHO FC and 6MWD were not improved significantly post‐BPA in PP patients. BPA response was not related to TTTL terciles or CTPA‐quantified residual disease burden. Patients PP experienced inferior response to BPA, despite similar baseline and procedural characteristics to IC. BPA does not abolish the relationship between TTTL and postsurgical PVR in PP patients, suggesting that BPA is less effective in treating residual PH after surgery in an experienced surgical center.

Efficacy of power assisted microdebrider in endoscopic adenoid resection

Background: Nasal obstruction, snoring, mouth breathing, ear ache is some of the most common problems encountered in pediatric otorhinolaryngological practice. The most common cause for the above symptoms is adenoid hypertrophy. Methods: Patients with age group of 4-16 years with symptoms of adenoid hypertrophy such as snoring, mouth breathing, ear ache and adenoid hypertrophy confirmed by Diagnostic Nasal Endoscopy and Radiological Investigations were included. Previous H/o surgery for adenoidectomy, bleeding disorders, cases with cleft palate or previous H/o cleft palate repair neuromuscular / craniofacial anomalies were excluded. Results: 3.10 mean grade was seen among study participants, with 39% of children having Grade 4 adenoids, 35% having Grade 3 adenoids, and 26% having Grade 2 adenoids. Snoring, nasal obstruction, and breathing scores all decreased statistically significantly. Conclusions: A microdebrider-assisted adenoidectomy has shown to provide full clearance with only a minor increase in haemorrhage and process time.

Challenges and Strategies for Developing Recombinant Vaccines against Leptospirosis: Role of Expression Platforms and Adjuvants in Achieving Protective Efficacy.

The first leptospiral recombinant vaccine was developed in the late 1990s. Since then, progress in the fields of reverse vaccinology (RV) and structural vaccinology (SV) has significantly improved the identification of novel surface-exposed and conserved vaccine targets. However, developing recombinant vaccines for leptospirosis faces various challenges, including selecting the ideal expression platform or delivery system, assessing immunogenicity, selecting adjuvants, establishing vaccine formulation, demonstrating protective efficacy against lethal disease in homologous challenge, achieving full renal clearance using experimental models, and reproducibility of protective efficacy against heterologous challenge. In this review, we highlight the role of the expression/delivery system employed in studies based on the well-known LipL32 and leptospiral immunoglobulin-like (Lig) proteins, as well as the choice of adjuvants, as key factors to achieving the best vaccine performance in terms of protective efficacy against lethal infection and induction of sterile immunity.

Evaluating the Efficacy of Pervistop®, a New Combination Based on EGCG, Folic Acid, Vitamin B12 and Hyaluronic Acid on Patients with Human Papilloma Virus (HPV) Persistent Infections and Cervical Lesions: A Pilot Study

The persistence of the HPV infection is a risk factor in the integration of viral DNA in the host genome, leading to transforming events. The lack of therapies for HPV-persistent infections determine an unmet medical need. We enrolled forty patients with persistent HPV infections and cervical lesions and divided them into two groups. The women in the treated group received 200 mg epigallocatechin gallate (EGCG), 400 µg folic acid (FA), 1 mg vitamin B12, and 50 mg hyaluronic acid (HA) for 12 weeks. The control group received no treatment. 40 patients completed the study. Fifteen out of 20 women in the control group still had an LSIL at the end of the study. One woman had a decrease in the DNA load, while six had no change and eight had an increase in DNA content. In the treatment group, 17 out of 20 women achieved a full viral clearance. These women showed no cytological or histological evidence of lesions following the treatment. Our data highlight the possible effect of such combination on LSIL. Therefore, the evidence reported here supports the potential to carry out further randomized placebo-controlled studies with an adequate number of patients to verify our results.