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Purpose: Anterior cruciate ligament repair techniques are of growing interest because they allow for minimally invasive surgery that avoids harvesting of the transplant, without risking growth deficiencies in young patients. The aim of this study is to summarize the published evidence about arthroscopic repair of anterior cruciate ligament proximal tears in skeletally immature patients.Methods: In total, four studies were included and processed for data extraction after screening for eligibility for this systematic review: one retrospective cohort study and three retrospective case series. Altogether, the four studies included in this review included 61 skeletally immature patients with a mean age of 12.1 years diagnosed with proximal anterior cruciate ligament tear who underwent arthroscopic repair with preservation of the native ligament. The mean follow-up period was 2.8 years.Results: The most relevant and objective outcome that we considered was re-rupture rate. One study reports a cumulative incidence of graft failure in the first 3 years after surgery of 48.8% while the others report a 0%, 0% and 21.5% re-rupture rate. No growth disturbances were reported in the included studies.Conclusion: Despite growing interest surrounding anterior cruciate ligament repair techniques, the presence of limited quality studies in the literature means repair cannot be strongly supported at present. Some encouraging data regarding the absence of growth disturbance and functional outcomes does exist, but studies with larger samples are required.Level of evidence: level IV.

Purpose: Over the last two decades the incidence of meniscal injuries has grown amongst the pediatric population predominantly due to greater involvement in sporting activities. The treatment and the natural history represent a socioeconomic burden for healthcare systems. This study demonstrates the epidemiology of meniscal tears treated surgically in Italy from 2010 to 2019 in a population up to 18 years. Methods: Data was collected from the National Archive of Hospital Discharges. ICD9-CM classification was used to select surgically treated meniscal injuries. Concomitant treatment of associated lesions were excluded. Data on the national population was retrieved from the Italian National Institute for Statistics (ISTAT). Statistical analyses were performed. Results: 17,449 isolated meniscal tears were surgically treated with a mean incidence of 20.6 per 100.000 in the Italian population aged up to 18 from 2010 to 2019. The mean age of patients was 15.85 with 89 % aged 14 or older. 30 % of the population was female. The incidence of medial meniscal surgery was higher than for the lateral meniscus. A declining trend in surgical incidence was observed. The mean hospitalization time was 1.53 days. Conclusions: Our study reveals a reduction in the total number of surgeries performed over the time frame and a significant rise in the incidence of meniscal lesions in pediatric patient above at the age of 13, especially in males. Despite a worldwide shift towards meniscal preservation, this trend is not evident in Italy as the current ICD9-CM classification does not differentiate between meniscectomy and meniscal repair, although an overall reduction in surgery may imply better management. Study design: Cohort study; Level of evidence III.

Background: Anterior cruciate ligament injury in the child and adolescent patient remains a controversial topic when considering management, especially regarding surgical choices. Treatment variations are seen not just when comparing different countries but also within nations. This arises partly as contemporary treatment is mostly inferred from the adult population who physiologically and in terms of outcomes differ significantly from children. There is an increasing body of evidence for this cohort of patients who have specific challenges and difficulties when determining the optimum treatment. Methods: Within this article, we will summarize the current evidence for surgical management of anterior cruciate ligament injury for the pediatric patient. Results and Conclusions: There remain many controversies and gaps inthe treatment of Paediatric Anterior cruciate ligament reconstruction and this high risk cohort continues to cause difficulty in identifying the best mode of surgical management. Level of evidence: level IV.

Osteochondritis dissecans of the knee is a disease that typically affects skeletally immature patients. Clinically manifested with knee pain, limping, and joint disfunction, this condition has remained misunderstood and undervalued for a long period. Although being a rare condition, its awareness is of utmost clinical interest because of the possible severe consequences it can bring when misrecognized or inadequately treated. Its etiology remains unclear and is still debated. Many theories have been proposed, including inflammation, local ischemia, subchondral ossification abnormalities, genetic factors, and repetitive mechanical microtrauma, with a likely interplay of the same. This review article aims to deliver and discuss current and up-to-date concepts on epidemiology, etiology, and natural history of this pediatric condition. Level of evidence: level V.

The development of early-onset cow’s milk protein allergy and atopic dermatitis during the first months of life is multifactorial, including both genetic and nutritional aspects. This study aims to assess the impact of different feeding patterns on the incidence of cow’s milk protein allergy, atopic dermatitis, and growth among infants with a family history of allergy. A total of 551 high-risk infants were randomly recruited from 3 European countries in three feeding regimens: exclusive breastfeeding, partially hydrolyzed formula, or standard formula with intact protein either exclusively or supplementary to breastfeeding. During the first 6 months of intervention, amongst infants with a family history of atopic dermatitis, 6.5% of partially hydrolyzed formula-fed infants and 22.7% of exclusively breastfed infants (p = 0.007) presented with atopic dermatitis respectively. Growth as assessed by weight increase did not differ between the aforementioned groups. Although cow’s milk protein allergy was not related to the different milk feeding regimens in the whole cohort, when adjusting for high breast milk intake, the respective incident was significantly lower in the infants consuming partially hydrolyzed formula (p < 0.001). This data indicates that a specific partially hydrolyzed formula could serve as a more appropriate complement to breast milk compared to a standard intact protein formula in high-risk infants, to reduce the incidence of atopic dermatitis. © 2023 by the authors.

Background: Lateral dislocation of the patella is a common injury in children. It can occur in previously healthy and anatomically normal knees, but there are several abnormalities that predispose to patellar instability. Magnetic resonance imaging is an essential part of assessing for associated injuries and risk of further instability. Treatment aims to prevent redislocation, residual instability, osteoarthritis, and allow return to previous activities. The purpose of this review was to assess evidence for management of first-time patella dislocation in children and adolescents. Methods: Literature review was performed, accompanied by the current best practice by the authors. Results: Non-operative treatment is preferred, except where there are associated injuries such as osteochondral fractures that would benefit from surgery. The exact method of ideal non-operative management is not clearly defined but should focus on restoration of range of movement and strength with bracing as indicated. There seems to be a trend toward operative intervention that may well be inappropriate. Conclusion: Further prospective studies are required with focus on the younger patient to fully understand if there is an at-risk group that would benefit from early surgery. Level of evidence:: level III.

Background: The role of partially hydrolyzed formulas (pHF) as part of nutritional interventions to prevent the development of allergic manifestations (AM) is questioned, and efficacy of each specific pHF should be substantiated. Objective: To investigate the risk-reduction effect of a whey-based pHF on the development of cow's milk protein allergy (CMPA) and atopic dermatitis (AD) in infants at high-risk for allergy within the first 6 months of life. Materials and Methods: In a multicenter double-blinded randomized controlled setting, healthy non-exclusively breastfed full-term infants, received either a specific whey-based pHF or a standard cow's milk-based formula (SF) and were clinically assessed for AM at 2, 4, and 6 months of age, supported by the objective scoring tools SCORAD and CoMiSS. CMPA was confirmed by open food challenge. Intention-to-Treat (ITT) and Per-Protocol (PP) analyses were performed. Results: Of 331 randomized subjects (ITT analysis set), 160 received the pHF and 171 the SF. Six (3.8%) infants in the pHF and 12 (7%) in the SF group developed CMPA (p = 0.186). AD incidence was significantly lower in those receiving pHF as compared to SF (10.6% vs. 18.7%, p = 0.024) with a relative risk (RR, 95% CI) of 0.54 (0.32, 0.92), in particular when adjusting for family history of AD [6.5% vs. 27.3%, RR 0.24 (0.07, 0.78), p = 0.018] representing a risk reduction of 76%. The PP analysis showed similar results. Conclusion: This specific whey-based pHF reduced the risk of AD development, particularly in those with a family history of AD, and tended to reduce the development of CMPA in non-exclusively breastfed infants at high-risk for allergy. The A.R.T. study suggests that this particular pHF may contribute to measures aimed at prevention of allergic manifestations. However, further studies are needed to confirm this risk-reduction effect. Copyright © 2022 Nicolaou, Pancheva, Karaglani, Sekkidou, Marinova-Achkar, Popova, Tzaki, Kapetanaki, Iacov

Abstract Background This study aimed to investigate overall and sex-specific excess all-cause mortality since the inception of the COVID-19 pandemic until August 2020 among 22 countries. Methods Countries reported weekly or monthly all-cause mortality from January 2015 until the end of June or August 2020. Weekly or monthly COVID-19 deaths were reported for 2020. Excess mortality for 2020 was calculated by comparing weekly or monthly 2020 mortality (observed deaths) against a baseline mortality obtained from 2015–2019 data for the same week or month using two methods: (i) difference in observed mortality rates between 2020 and the 2015–2019 average and (ii) difference between observed and expected 2020 deaths. Results Brazil, France, Italy, Spain, Sweden, the UK (England, Wales, Northern Ireland and Scotland) and the USA demonstrated excess all-cause mortality, whereas Australia, Denmark and Georgia experienced a decrease in all-cause mortality. Israel, Ukraine and Ireland demonstrated sex-specific changes in all-cause mortality. Conclusions All-cause mortality up to August 2020 was higher than in previous years in some, but not all, participating countries. Geographical location and seasonality of each country, as well as the prompt application of high-stringency control measures, may explain the observed variability in mortality changes.

BACKGROUND: Understanding the impact of the burden of COVID-19 is key to successfully navigating the COVID-19 pandemic. As part of a larger investigation on COVID-19 mortality impact, this study aims to estimate the Potential Years of Life Lost (PYLL) in 17 countries and territories across the world (Australia, Brazil, Cape Verde, Colombia, Cyprus, France, Georgia, Israel, Kazakhstan, Peru, Norway, England & Wales, Scotland, Slovenia, Sweden, Ukraine, and the United States [USA]). METHODS: Age- and sex-specific COVID-19 death numbers from primary national sources were collected by an international research consortium. The study period was established based on the availability of data from the inception of the pandemic to the end of August 2020. The PYLL for each country were computed using 80 years as the maximum life expectancy. RESULTS: As of August 2020, 442,677 (range: 18-185,083) deaths attributed to COVID-19 were recorded in 17 countries which translated to 4,210,654 (range: 112-1,554,225) PYLL. The average PYLL per death was 8.7 years, with substantial variation ranging from 2.7 years in Australia to 19.3 PYLL in Ukraine. North and South American countries as well as England & Wales, Scotland and Sweden experienced the highest PYLL per 100,000 population; whereas Australia, Slovenia and Georgia experienced the lowest. Overall, males experienced higher PYLL rate and higher PYLL per death than females. In most countries, most of the PYLL were observed for people aged over 60 or 65 years, irrespective of sex. Yet, Brazil, Cape Verde, Colombia, Israel, Peru, Scotland, Ukraine, and the USA concentrated most PYLL in younger age groups. CONCLUSIONS: Our results highlight the role of PYLL as a tool to understand the impact of COVID-19 on demographic groups within and across countries, guiding preventive measures to protect these groups under the ongoing pandemic. Continuous monitoring of PYLL is therefore needed to better understand the burden of COVID-19 in terms of

Goldberg–Shprintzen syndrome (GOSHS) is caused by loss of function variants in the kinesin binding protein gene (KIFBP). However, the phenotypic range of this syndrome is wide, indicating that other factors may play a role. To date, 37 patients with GOSHS have been reported. Here, we document nine new patients with variants in KIFBP: seven with nonsense variants and two with missense variants. To our knowledge, this is the first time that missense variants have been reported in GOSHS. We functionally investigated the effect of the variants identified, in an attempt to find a genotype–phenotype correlation. We also determined whether common Hirschsprung disease (HSCR)‐associated single nucleotide polymorphisms (SNPs), could explain the presence of HSCR in GOSHS. Our results showed that the missense variants led to reduced expression of KIFBP, while the truncating variants resulted in lack of protein. However, no correlation was found between the severity of GOSHS and the location of the variants. We were also unable to find a correlation between common HSCR‐associated SNPs, and HSCR development in GOSHS. In conclusion, we show that reduced, as well as lack of KIFBP expression can lead to GOSHS, and our results suggest that a threshold expression of KIFBP may modulate phenotypic variability of the disease.

Goldberg-Shprintzen syndrome (GOSHS) is caused by loss of function variants in the kinesin binding protein gene (KIFBP). However, the phenotypic range of this syndrome is wide, indicating that other factors may play a role. To date, 37 patients with GOSHS have been reported. Here, we document nine new patients with variants in KIFBP: seven with nonsense variants and two with missense variants. To our knowledge, this is the first time that missense variants have been reported in GOSHS. We functionally investigated the effect of the variants identified, in an attempt to find a genotype-phenotype correlation. We also determined whether common Hirschsprung disease (HSCR)-associated single nucleotide polymorphisms (SNPs), could explain the presence of HSCR in GOSHS. Our results showed that the missense variants led to reduced expression of KIFBP, while the truncating variants resulted in lack of protein. However, no correlation was found between the severity of GOSHS and the location of the variants. We were also unable to find a correlation between common HSCR-associated SNPs, and HSCR development in GOSHS. In conclusion, we show that reduced, as well as lack of KIFBP expression can lead to GOSHS, and our results suggest that a threshold expression of KIFBP may modulate phenotypic variability of the disease.