Patellar osteochondritis dissecans: maturation-dependent patellofemoral joint characteristics.

BACKGROUND: The likelihood of healing of osteochondritis dissecans decreases with skeletal maturity and there are theories that abnormal biomechanical forces contribute to the development and progression of these lesions. OBJECTIVE: To characterize, according to regional skeletal maturity, the morphology and alignment indices of the patellofemoral joint on MRI in patients with patellar osteochondritis dissecans. MATERIALS AND METHODS: MRI examinations of patients with patellar osteochondritis dissecans obtained between January 2008 and May 2023 were retrospectively reviewed to determine regional skeletal maturity, osteochondritis dissecans lesion size and location, patellar and trochlear morphology (Wiberg/Dejour classifications), and to calculate trochlear sulcus angles, trochlear depth index, lateral trochlear inclination, Insall-Salvati index, Caton-Deschamps index, patellar tendon-lateral trochlear ridge, and tibial tubercle-trochlear groove distances. Values were compared between skeletally immature and mature groups. RESULTS: Sixty-eight children (22 girls, 46 boys, age: 14.0 ± 1.7 years) yielded 74 knees with patellar osteochondritis dissecans lesions, 14 (19%) of which were skeletally mature. The most common anatomic location was over the central patella [median ridge (34/74 - 46%) on the axial images and over the middle third (45/74 - 61%) on the sagittal images]. Overall, mean trochlear sulcus angle (high, 151 ± 11°), trochlear depth index (low, 2.8 ± 1.4 mm), and Insall-Salvati index (borderline, 1.3 ± 0.1) were abnormal for the entire sample. Skeletally mature knees were significantly more likely to have higher (more dysplastic) Dejour types when compared to skeletally immature knees (p < 0.01). Knees in the mature group, compared to immature, had significantly more abnormal mean lateral trochlear inclination (15 ± 8° vs. 19 ± 6°, p = 0.03) and patellar tendon-lateral trochlear ridge distance (5.55 ± 4.31 mm vs. 2.89 ± 4.69 mm, p = 0.04). Half of the knees had ≥ 4 abnormal features that predispose to patellofemoral maltracking; mature knees were significantly (p = 0.02) more likely to have a higher number of abnormal features (> 6 features, 7/14, 50.0%) versus immature knees (0-3 features, 33/60, 55.0%). CONCLUSION: In children with patellar osteochondritis dissecans, abnormal patellofemoral morphology and alignment indices were common in all patients and more severe in mature knees.

Not Just Small Adults: Operative Versus Nonoperative Treatment in Adolescent Tibial Shaft Fractures.

BACKGROUND: The standard of care for tibial shaft fractures in young children is nonoperative management, while in adults, operative treatment is considered the mainstay. There are no clear guidelines on preferred treatment for adolescents. PURPOSE: This paper aims to 1) identify clinical and radiographic characteristics predictive of malalignment and 2) determine if treatment type affects malalignment risk. METHODS: This retrospective cohort study identified patients aged 12 to 16 years old with a tibial shaft fracture at a Level 1 pediatric trauma center. The primary outcome of interest was malalignment, classified as meeting one or more of the following: >5° coronal angulation, >5° sagittal angulation, translation (cortical width or 100% displaced), and/or rotational deformity. Comparative analyses were done to identify risk factors for malalignment. RESULTS: A total of 162 patients were included-initial treatment was "planned nonoperative" for 102 patients and "planned operative" for 60 patients. The malalignment rate was 34% in the planned nonoperative group versus 32% in the planned operative group. In a multivariate regression, older patients [odds ratio (OR)=-0.07, 95% CI: -0.13 to -0.01; P =0.024] and those with 100% initial displacement (OR=-0.35, 95% CI: -0.64 to -0.05; P =0.021) had decreased odds of malalignment, and having increased sagittal angulation (OR=0.02, 95% CI: 0.01-0.04; P =0.002) and a fibula fracture (OR=0.22, 95% CI: 0.03-0.41; P =0.023) increased the odds of malalignment. There was no difference in the rate of malalignment by initial treatment ( P =0.289). Having a planned nonoperative treatment (OR=22.7, 95% CI: 14.0-31.5; P <0.001) and having a fibula fracture (OR=8.52, 95% CI: 0.59-16.45; P =0.035) increased the time immobilized. CONCLUSIONS: This study provides insight into factors affecting tibial shaft fracture alignment among patients aged 12 to 16 years. This study suggests that the risk of malalignment is higher among patients with increased initial sagittal angulation and concomitant fibula fractures, but the risk of malalignment is comparable in patients initially treated nonoperatively and operatively. Although healing parameters on average were similar, nonoperative treatment results in longer immobilization time and time for unrestricted weight bearing. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

Patella and Trochlea Osteochondritis Dissecans: Demographics and Treatment Paradigms.

OBJECTIVE: Previous research on patellar and trochlear groove osteochondritis dissecans (OCD) is limited by small sample sizes. This study aims to describe the presentation of patients with OCD lesions of the patella and trochlea and characterize the outcomes of operative and nonoperative treatments. METHODS: This retrospective cohort study identified all patients from a single institution from 2008 to 2021 with patellar and/or trochlear OCD lesions. Patients were excluded from the study if surgical records were unavailable or if the patient had knee surgery for a different injury at index surgery or in the 12 months postoperative. Minimum follow-up was 12 months. Outcomes included a return to sports (RTS), pain resolution, radiographic healing, and treatment "success" (defined as full RTS, complete pain resolution, and full healing on imaging). RESULTS: A total of 68 patients (75 knees) were included-45 (60%) with patellar OCD and 30 (40%) with trochlear. Of the patients, 69% were males. The median age at knee OCD diagnosis was 14 years. At the final follow-up, 62% of knees (n = 44) recovered sufficiently to allow a full RTS and 54% of knees (n = 39) had full pain resolution. Of the 46 knees with radiographic imaging at least 1 year apart, 63% had full healing of the lesion. There was no significant difference in RTS, pain resolution, radiographic healing, or overall success when comparing treatments. CONCLUSIONS: This study provides valuable epidemiologic demographic and outcome data regarding the scarcely reported patellar and trochlear OCD. While over half of patients fully returned to sports and reported full pain resolution, a large proportion continued to experience symptoms over a year after presentation. Future research should aim to better define the treatment algorithms for these OCD subtypes. LEVEL OF EVIDENCE: Level III.

Current Treatment Landscape for Dystrophic Epidermolysis Bullosa: From Surgical Management to Emerging Gene Therapies and Novel Skin Grafts.

Epidermolysis bullosa is a genetic skin disorder characterized by blister formation from mechanical trauma. Dystrophic epidermolysis bullosa (DEB) is caused by mutations in the COL7A1 gene presenting as generalized blisters from birth, which can result in extensive scarring, alopecia, esophageal stenosis, corneal erosions, and nail dystrophy. This disease also often leads to pseudosyndactyly of the digits from the closure of webspaces, progressing to a "mitten hand" deformity. Although traditional and current treatment for DEB is largely supportive with wound care and iterative surgical pseudosyndactyly release, emerging gene therapies and novel skin grafts may offer promising treatment. Studies published in the early 2020s have used HSV-1 vectors expressing missing COL7A1 genes to restore collagen function. One of these treatments, B-VEC, is an HSV-1-based topical gene therapy designed to restore collagen 7 by delivering the COL7A1 gene, leveraging a differentiated HSV-1 vector platform that evades the patient's immune system response. Other work has been performed to retrovirally modify autologous keratinocytes, but limitations of this process include increased labor in harvesting and engineering autologous cells. This article provides an overview of DEB treatment with an emphasis on emerging gene therapies and novel skin grafts, especially as they pertain to pseudosyndactyly treatment.

Disparate Impact: How Does Social Deprivation Affect Patient-reported Outcomes After ACL Reconstruction in Children and Adolescents?

BACKGROUND: Research has indicated that lower socioeconomic status is associated with delays in the treatment of anterior cruciate ligament (ACL) injuries; however, there is a paucity of literature evaluating its association with patient-reported outcomes (PROs). Using the Area Deprivation Index (ADI), a validated proxy for socioeconomic status, the study aimed to determine how relative socioeconomic disadvantage is related to PROs after primary ACL reconstruction (ACLR) in pediatric patients. METHODS: This retrospective cohort study included all patients 18 years old or above who underwent primary ACLR at an academic institution between 2018 and 2021. Exclusion criteria included multiligament injury, congenital ACL absence, and absent outcomes data. The minimum follow-up was 6 months. A Patient-reported Outcomes Measurement Information System (PROMIS) 50 Pediatric self-report questionnaire was completed at postoperative visits, and domain scores for pain, physical function/mobility, fatigue, anxiety, depression, and peer relationships were generated. The National ADI percentile was calculated using the patients' addresses. Patients were divided into quartiles (low, moderate, moderate-severe, and severe ADI), and comparative analyses were performed to determine the relationship between ADI and PROMIS. RESULTS: A total of 413 patients were identified, including 49% (n=207), 33% (n=139), 11% (n=48), and 7% (n=30) from the low, moderate, moderate-severe, and severe deprivation areas, respectively. As compared with those in the low-deprivation quartile, patients in the severe deprivation quartile had delayed time to the first clinic visit (11 vs. 16.5 d, P=0.044) and surgery (51 vs. 80 d, P=0.004). There were no differences in the number of additional procedures required at index surgery. All quartiles had progressive improvements in physical function/mobility and pain scores throughout recovery, but at 9 months, there was significantly more pain in the severe deprivation cohort, despite no difference in self-reported physical function and mobility. Those with severe socioeconomic disadvantage had worse psychosocial outcomes, including significantly increased depression, fatigue, and anxiety and decreased peer relationship scores. CONCLUSIONS: Although there were no differences in preoperative PROMIS scores, pediatric patients living in areas with higher levels of socioeconomic deprivation/disadvantage had worse psychosocial PROs after ACLR. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

Why Don't Adolescents Wear Their Brace? A Prospective Study Investigating Psychosocial Characteristics That Predict Scoliosis Brace Wear.

BACKGROUND: Although bracing for adolescent idiopathic scoliosis can prevent curve progression and reduce the risk for future surgery, children frequently do not wear their braces as prescribed. The purpose of this study is to investigate how a broad array of psychosocial characteristics predict future compliance with scoliosis brace wear. METHODS: This was a single institution, prospective cohort study. All adolescents prescribed a first-time brace for adolescent idiopathic scoliosis were eligible. Patients and their parents completed a separate series of questionnaires that assessed baseline psychosocial characteristics across 6 domains: (1) brace-specific attitudes; (2) body image and self-esteem; (3) school performance and social relationships; (4) psychological health; (5) family functioning; and (6) demographics and scoliosis-specific details (242 total questions across 12 validated questionnaires). Objective brace compliance was collected using temperature-sensitive monitors. Defining compliance as percentage of brace prescription completed, comparative analyses were performed to identify baseline psychosocial characteristics that were associated with future wear. A composite measure (Bracing Fidelity Follow-Up Scale [BFFS]) of the 12 most predictive individual questions across all domains (both parent and adolescent) was constructed to help assess which adolescents were at highest risk of failure to wear their brace. Total BFFS score for each parent-adolescent dyad who completed all the included surveys was then determined by awarding one point for each factor that positively influenced future brace wear (maximum 12 points), and a correlation was calculated between total score and percent adherence to prescribed brace wear. RESULTS: A total of 41 patients were included. On average, patients with high self-esteem, above average peer relationships and poor brace-specific attitudes had lower brace compliance, although patients with increased loneliness and parental religiousness had higher compliance. Body image, socioeconomic status, family dynamics, and school performance had no significant relationship with brace use. Total score on the Bracing Fidelity Follow-Up Scale (BFFS) was significantly associated with improved brace wear (r=0.687, P <0.001). Those with a score of 6 or above (n=15/33 [45%], median compliance 96%) were more reliable users (15/15 with compliance >75%), and those with a score of 5 or less (n=18/33 [55%], median compliance 50%) had less consistent brace wear (9/18 with compliance <50%). CONCLUSION: This prospective study identifies numerous baseline psychosocial factors that are associated with future compliance with scoliosis brace wear. Although in need of further validation before widespread clinical application, the novel BFF scale offers a potential opportunity to partially discriminate between compliant and noncompliant scoliosis brace users such that supportive resources (eg, supportive counseling, peer-support groups, additional provider-based education, etc.) can be targeted to those patients most likely to benefit. LEVEL OF EVIDENCE: II.

A Prospective, Multicenter Study of Developmental Dysplasia of the Hip: What Can Patients Expect After Open Reduction?

BACKGROUND: Although there are several predominantly single-center case series in the literature, relatively little prospectively collected data exist regarding the outcomes of open hip reduction (OR) for infantile developmental dysplasia of the hip (DDH). The purpose of this prospective, multi-center study was to determine the outcomes after OR in a diverse patient population. METHODS: The prospectively collected database of an international multicenter study group was queried for all patients treated with OR for DDH. Minimum follow-up was 1 year. Proximal femoral growth disturbance (PFGD) was defined by consensus review using Salter's criteria. Persistent acetabular dysplasia was defined as an acetabular index >90th percentile for age. Statistical analyses were performed to compare preoperative and operative characteristics that predicted re-dislocation, PFGD, and residual acetabular dysplasia. RESULTS: A cohort of 232 hips (195 patients) was identified; median age at OR was 19 months (interquartile range 13 to 28) and median follow-up length was 21 months (interquartile range 16 to 32). Re-dislocation occurred in 7% of hips (n=16/228). The majority (81%; n=13/16) occurred in the first year after initial OR. Excluding patients with repeat dislocation, 94.5% of hips were IHDI 1 at most recent follow-up. On the basis of strict radiographic review, some degree of PFGD was present in 44% of hips (n=101/230) at most recent follow-up. Seventy-eight hips (55%) demonstrated residual dysplasia compared with established normative data. Hips that had a pelvic osteotomy at index surgery had about half the rate of residual dysplasia (39%; n=32/82) versus those without a pelvic osteotomy with at least 2 years follow-up (78%; n=46/59). CONCLUSIONS: In the largest prospective, multicenter study to date, OR for infantile DDH was associated with a 7% risk of re-dislocation, 44% risk of PFGD, and 55% risk of residual acetabular dysplasia at short term follow-up. The incidence of these adverse outcomes is higher than previous reports. Patients treated with concomitant pelvic osteotomy had lower rates of residual dysplasia. These prospectively collected, multicenter data provide better generalizable information to improve family education and appropriately set expectations. LEVEL OF EVIDENCE: Level II, prospective comparative study.

The Epidemiology of Pediatric Basketball Injuries Presenting to US Emergency Departments: 2011-2020.

OBJECTIVES: The purpose of this study is to describe the national epidemiology of basketball-related injuries in children and adolescents presenting to US emergency departments (EDs) from 2011 to 2020 and to quantify the effect of the COVID-19 pandemic. METHODS: The National Electronic Injury Surveillance System database was queried for cases of injury in persons aged 0 to 19 years related to product code 1205 (basketball and related equipment) presenting from January 1, 2011 to December 31, 2020. National injury estimates were calculated using National Electronic Injury Surveillance System-recommended weights and strata. The US Census data were used to determine the incidence of injury by age group and by sex. To quantify the effect of COVID-19, an interrupted time series analysis was performed using March 1, 2020 as the interrupting time point. The pre-COVID-19 trend was used to estimate the difference in injuries attributable to the COVID-19 pandemic. RESULTS: From 2011 to 2020, an estimated 3,210,953 (95% confidence interval = 2,655,812-3,788,094) visits were made to US EDs for basketball-related injuries in those aged younger than 20 years, corresponding to a mean annual incidence of 391 injuries per 100,000 population. The mean age of injury was 14.4 years (95% confidence interval = 14.3-14.5). Boys were more often injured than girls (76% vs 24% of all injuries, respectively). The foot was the most injured body part, accounting for 24% of injuries. Strains or sprains were the most common injury type (38% of injuries). During the COVID-19 pandemic, there were 155,638 fewer injuries than were expected based on pre-COVID-19 trends. During COVID-19, there were no significant differences in the proportions of injury types, body parts involved, sex, or age. CONCLUSIONS: Basketball remains a frequent cause of injury, especially in adolescents. The COVID-19 pandemic profoundly reduced the frequency of basketball-related injuries, but did not affect the type and body location of injuries presenting to the ED.

Wernicke's encephalopathy secondary to hyperemesis gravidarum: A clinical challenge.

Wernicke's encephalopathy (WE) is an acute neurological condition characterized by a triad of ophthalmoplegia, ataxia and altered mental status. The underlying cause is thiamine deficiency, which may be due to multiple aetiologies. Thiamine is essential for carbohydrate and amino acid metabolism. Its deficiency shunts glucose to anaerobic pathways producing metabolic abnormalities. Diagnosing WE relies heavily on clinical suspicion. Magnetic Resonance Imaging can show some specific findings. We report this case of a 35 year old pregnant woman with gestational diabetes who was admitted in hospital for high blood sugar levels and electrolyte abnormalities. She had a history of ten miscarriages. From undergoing laparoscopic cholecystectomy for intractable vomiting to spontaneous expulsion of the foetus to being intubated for acidosis, her hospital stay was prolonged and eventful. Although the cause of her repeated miscarriages could not be established despite extensive workup, thiamine deficiency leading to Wernicke's encephalopathy was the most probable cause.

Hospital-Specific Total Joint Arthroplasty Casemix and Patient Flows in the Era of Payment Reform: Impact on Resource Utilization Among New York State Hospitals.

BACKGROUND: Bundled payment models may lead to selection of healthier total joint arthroplasty (TJA) candidates resulting in comorbid patients being taken care of in fewer hospitals. We aimed to (1) evaluate hospital-specific TJA comorbidity burden ("casemix") over time and (2) associations with resource utilization. METHODS: This retrospective cohort study used 2011 and 2016 New York State data (n = 36,078 hip/knee arthroplasties). Comorbidity burden was estimated by the Charlson-Deyo Index; main outcomes were hospitalization cost and nonhome discharge. Hospitals were categorized into those with a decreased, stable (with a 5% buffer), or increased percentage of comorbidity-free patients (Charlson-Deyo = 0) between 2011 and 2016. Mixed-effects models measured the association between Charlson-Deyo Index category and outcomes, by hospital casemix categorization. Odds ratios and 95% confidence intervals (CIs) are reported. RESULTS: Overall, 29 (n = 8810), 37 (n = 16,297), and 46 (n = 10,971) hospitals were categorized into the decreased, stable, and increased Charlson-Deyo = 0 categories, respectively, with median annual TJA volumes of 499, 814, and 393 (P < .0001). Multivariable models demonstrated that-in hospitals with a stable patient casemix-increased patient comorbidity was associated with increased hospitalization costs (maximum 21.8%, CI 18.9-24.9, P < .0001). However, this effect was moderated (maximum 11.1%, CI 8.0-14.2) in hospitals that took on a more comorbid patient casemix. Similar patterns were observed for nonhome discharge. CONCLUSION: Most studied hospitals show an increase in comorbidity-free TJA patients, suggestive of patient selection. This redistribution of comorbid patients to select hospitals may not necessarily be a negative development as our results suggest more efficient resource utilization for comorbid patients in such hospitals.

Correlation of Dietary Intake and Helicobacter pylori Infection with Multiple Sclerosis, a Case-Control Study in Rafsanjan, Iran, 2017-18.

BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease affecting the central nervous system. Some environmental factors, such as Helicobacter pylori infection (HPI), are likely to be considered a protective factor in MS. Dietary intake may provide exposure to or have protective effects for MS. The present study aimed to determine the relationship between serum anti-H. pylori IgG antibody (HPIA) level and dietary intake in patients with MS referred to the MS Clinic in Rafsanjan city, Iran. METHODS: The present case-control study was conducted on 97 patients with MS and 95 controls. The two groups had no significant difference in age and gender (p > 0.05). HPIA was checked, and the food frequency questionnaire was completed in both groups to measure nutritional intake. All data were analyzed by the SPSS 20 software using independent t-test, Chi-Square, Mann-Whitney U test, and correlation. RESULTS: The median serum HPIA level was significantly lower in MS cases than in controls. Furthermore, the median consumption of glutamic acid, arginine, serine, aspartic acid, alanine, proline, and caffeine was significantly lower in MS cases than in controls. A significant positive correlation was found between the levels of linoleic acid, lactose, Ca, molybdenum, galactose, leucine, and valine, and the level of HPIA in controls. CONCLUSION: Our study results demonstrated that some dietary nutrients had correlations with MS and HPI. Therefore, professionals from multiple disciplines must find which foods contain these dietary nutrients in future studies.

Correlates of viral suppression among HIV-infected men who have sex with men and transgender women in Lima, Peru.

In Peru, HIV is concentrated among men who have sex with men (MSM) and transgender women (TGW). Between June 2015 and August 2016, 591 HIV-positive MSM and TGW were recruited at five clinical care sites in Lima, Peru. We found that 82.4% of the participants had achieved viral suppression (VS; VL < 200) and 73.6% had achieved maximal viral suppression (MVS; VL < 50). Multivariable modeling indicated that patients reporting transportation as a barrier to HIV care were less likely to achieve VS (aOR = 0.47; 95% CI = 0.30-0.75) and MVS (aOR = 0.56; 95% CI = 0.37-0.84). Alcohol use disorders were negatively associated with MVS (aOR = 0.62; 95% CI = 0.30-0.75) and age was positively associated with achieving MVS (aOR = 1.29; 95% CI = 1.04-1.59). These findings underscore the need for more accessible HIV care with integrated behavioral health services in Lima, Peru.

Delivery mode and breastfeeding outcomes among new mothers in Nicaragua.

Breastfeeding has been shown to benefit infants and mothers. Women who have caesarean deliveries (C-sections) are expected to be less likely to initiate and continue breastfeeding than those who have vaginal deliveries. Given the high rate of C-sections in Nicaragua, the importance of breastfeeding, and the centrality of culture in choices about breastfeeding, this study sought to examine if mode of delivery relates with breastfeeding initiation and exclusivity in Nicaragua. Two hundred fifty mothers were surveyed about birth experiences and breastfeeding behaviour in 3 public clinics in León, Nicaragua, between June and August 2015. Logistic regression analyses were performed to examine the association of mode of delivery with initiation of breastfeeding within 1 hr of birth (early initiation) and exclusive breastfeeding for 6 months post-partum. The rate of early initiation was 68.8% and that of exclusively breastfeeding for 6 months was 12.7%. Mode of delivery was not significantly associated with early initiation (p = .383) or exclusive breastfeeding (p = .518). Early initiation was negatively associated with prelacteal feeding, AOR = 0.30, 95% CI [0.16, 0.58]; p = .001. Mothers who had perceived their infants as large at birth were significantly less likely to exclusively breastfeed for 6 months, AOR (95%CI) = 0.25 (0.06-0.97); p = 0.046. Mode of delivery was not significantly associated with optimal breastfeeding initiation and exclusivity among mothers in Nicaragua. The 2 risk factors identified for delayed initiation of breastfeeding and lack of exclusive breastfeeding were prelacteal feeding and maternal perception of a large infant at birth, respectively.

Determinants of perceived insufficient milk among new mothers in León, Nicaragua.

Breastfeeding has been shown to improve maternal and child health. In Nicaragua, the primary risk of death and disability-adjusted life years among children under 5 years of age is suboptimal breastfeeding. Although the Nicaraguan Ministry of Health promotes exclusive breastfeeding from within the first half hour through the first 6 months of life, less than a third of children in the country under 6 months of age are exclusively breastfed. As part of a larger, mixed-methods study, 21 semi-structured, in-depth interviews were conducted with new mothers recruited from three primary health centers between June and August 2015 in order to identify the social, cultural, and structural factors that contribute to infant feeding practices and the discrepancy between recommendations and practices among mothers who delivered at an urban public hospital in León, Nicaragua. Audio recordings were transcribed verbatim, and interview transcripts were coded and analyzed by a three-member team using a grounded theory approach. Findings highlight a widespread perception of insufficient milk among mothers that influenced early cessation of exclusive breastfeeding and other infant feeding practices. This perception stemmed from anxiety about meeting infant nutritional needs and infant satiety, anxiety about maternal nutrition, advice from and role modeling of family members about mixed feeding, and perceived infant feeding norms. Results suggest that support modeled after the 10 steps of the Baby-friendly Hospital Initiative as well as strengthened policy-level support are needed. Community interventions that address cultural and structural barriers to improve breastfeeding practices may also help to increase breastfeeding rates.

Harnessing entropic and enthalpic contributions to create a negative tone chemically amplified molecular resist for high-resolution lithography.

Here we present a new resist design concept. By adding dilute cross-linkers to a chemically amplified molecular resist, we synergize entropic and enthalpic contributions to dissolution by harnessing both changes to molecular weight and changes in intermolecular bonding to create a system that outperforms resists that emphasize one contribution over the other. We study patterning performance, resist modulus, solubility kinetics and material redistribution as a function of cross-linker concentration. Cross-linking varies from dilute oligomerization to creating a highly networked system. The addition of small amounts of cross-linker improves resist performance by reducing material diffusion and redistribution during development and stiffening the features to avoid pattern collapse. The new dilute cross-linking system achieves the highest resolution of a sensitive molecular glass resist at 20 nm half-pitch and line-edge roughness (LER) of 4.3 nm and can inform new resist design towards patterned feature control at the molecular level.

L-lysine Increases the Anticancer Effect of Doxorubicin in Breast Cancer by Inducing ROS-Dependent Autophagy.

BACKGROUND: Doxorubicin (DOX) is a chemotherapy drug that is widely used in cancer therapy, especially in Triple-Negative Breast Cancer (TNBC) patients. Nevertheless, cytoprotective autophagy induction by DOX limits its cytotoxic effect and drug resistance induction in patients. Therefore, finding a new way is essential for increasing the effectiveness of this drug for cancer treatment. OBJECTIVE: This study aimed to investigate the effect of L-lysine on DOX cytotoxicity, probably through autophagy modulation in TNBC cell lines. METHODS: We used two TNBC cell lines, MDA-MB-231 and MDA-MB-468, with various levels of autophagy activity. Cell viability after treatment with L-lysine alone and in combination therapy was evaluated by MTT assay. Reactive Oxygen Species (ROS), nitric oxide (NO) concentration, and arginase activity were assessed using flow cytometric analysis, Griess reaction, and arginase activity assay kit, respectively. Real-time PCR and western blot analysis were used to evaluate the L-lysine effect on the autophagy-related genes and protein expression. Cell cycle profile and apoptotic assay were performed using flow cytometric analysis. RESULTS: The obtained data indicated that L-lysine in both concentrations of 24 and 32 mM increased the autophagy flux and enhanced the DOX cytotoxicity, especially in MDA-MB-231, which demonstrated higher autophagy activity than MDA-MB-468, by inducing ROS and NO production. Furthermore, L-lysine induced G2/M arrest autophagy cell death, while significant apoptotic changes were not observed. CONCLUSION: These findings suggest that L-lysine can increase DOX cytotoxicity through autophagy modulation. Thus, L-lysine, in combination with DOX, may facilitate the development of novel adjunct therapy for cancer.

Therapeutic potential of exosomes derived from mesenchymal stem cells for treatment of systemic lupus erythematosus.

Autoimmune diseases are caused by an imbalance in the immune system, producing autoantibodies that cause inflammation leading to tissue damage and organ dysfunction. Systemic Lupus Erythematosus (SLE) is one of the most common autoimmune diseases and a major contributor to patient morbidity and mortality. Although many drugs manage the disease, curative therapy remains elusive, and current treatment regimens have substantial side effects. Recently, the therapeutic potential of exosomes has been extensively studied, and novel evidence has been demonstrated. A direct relationship between exosome contents and their ability to regulate the immune system, inflammation, and angiogenesis. The unique properties of extracellular vesicles, such as biomolecule transportation, biodegradability, and stability, make exosomes a promising treatment candidate for autoimmune diseases, particularly SLE. This review summarizes the structural features of exosomes, the isolation/purification/quantification method, their origin, effect, immune regulation, a critical consideration for selecting an appropriate source, and their therapeutic mechanisms in SLE.

Human placental mesenchymal stromal cell-derived small extracellular vesicles as a treatment for severe COVID-19: A double-blind randomized controlled clinical trial.

The current study aimed to investigate the effects of human placental mesenchymal stromal cell-derived small extracellular vesicles (hPMSC-sEVs) as a treatment for COVID-19. This double-blind, randomized, controlled clinical trial was conducted on two groups of patients with COVID-19-associated acute respiratory distress syndrome. After randomization, the control group received standard treatment and placebo, and the intervention arm received standard treatment plus hPMSC-sEVs. The number of hospital deaths was considered the primary outcome. After meeting the exclusion and inclusion criteria, 21 and 24 patients were allocated to intervention and control arms, respectively. Besides admission SpO2 levels, which were significantly lower in the intervention arm (p = 0.008), all the baseline demo-biographic and laboratory variables were similar between the groups. It was shown that hPMSC-sEVs could significantly (p = 0.015) decrease the mortality ratio in the intervention group (4/21 [19.04%]) compared to the controls (13/24 [54.16%]). The mean time to death in the intervention and control groups was 28.06 and 11.10 days, respectively (p < 0.001). This study showed that hPMSC-sEVs are a possible treatment for critically ill patients with COVID-19.

Ambulatory Surgery Center in Rural Uganda: A Novel Approach to Providing Surgical Care.

BACKGROUND: Despite evidence that ambulatory surgery is safe with faster recovery compared to in-patient hospitalization, surgeons in low- and middle-income countries like Uganda have been hesitant to embrace this practice. Kyabirwa Surgical Center (KSC) is the first freestanding ambulatory surgery center (ASC) in rural Uganda. We aim to report the impact of a rural ASC since its establishment, in alleviating surgically-treatable morbidity within its catchment area. METHODS: KSC is located in Jinja, Uganda. The center's electronic medical record was used to analyze the utilization of services, and the Uganda Bureau of Statistics was used to calculate KSC's catchment area. Effectiveness was calculated using disability-adjusted life years (DALYs) averted. RESULTS: Between July 2019 and December 2021, 7,391 patients (57.7% female, 42.3% male) visited KSC from a catchment area of 570,790 people. Of 1,355 procedures, 64.6% were general surgery, 21.3% endoscopy, 9.2% gynecological/genitourinary), 2.8% ENT, 1.5% colorectal, and 0.6% orthopedics. There were no postoperative hospital admissions for complications or mortalities. From the seven most common procedures with an associated disability weight, 2,193.16 total DALYs were averted. CONCLUSION: ASCs can be effective in addressing surgical care gaps in Uganda by increasing the yearly surgical capacity of the local catchment area and averting DALYs within the population.

Clubfoot and the Ponseti Method: A Bibliometric Analysis.

Background: The aim of the present study was to perform a bibliometric analysis of research articles published on clubfoot to provide a quantitative description of the literature and to gather information on the institutions, journals, researchers, and countries publishing on this topic. Methods: This bibliometric analysis consisted of 2 Web of Science searches. The first identified all articles published prior to April 25, 2022, with "clubfoot" in the title, abstract, or keywords, and the second identified all articles with "Ponseti." Studies were exported in BibTeX format and uploaded into Biblioshiny software in RStudio. Descriptive statistics are reported for variables related to the article, author, and country in which the research was conducted. Results: A total of 2,177 articles identified using the term "clubfoot" were included. The first article was published in 1902, and there was a 3% annual growth rate. A total of 762 articles identified using the term "Ponseti" were included, with the first published in 1992 and a 13.9% annual growth rate. The Journal of Pediatric Orthopaedics accounted for almost one-quarter of all published reports. Conclusions: The literature on clubfoot has expanded in the past decades, and the percentage of studies concerning the Ponseti method has increased dramatically in the years following adoption in the U.S. and, more recently, globally. While a number of studies involved collaboration between authors in high-income and low- and middle-income countries, further collaboration will be essential to evaluate outcomes and help improve service delivery as adoption of this method increases globally. Clinical Relevance: This paper explores how the orthopaedic and scientific communities have increasingly contributed to literature on Ponseti casting and clubfoot, and discusses how contributions to the literature are becoming increasingly widespread.