As the survival rates of very low birth weight (VLBW) infants have increased, their neurodevelopmental outcomes are of concern. This study aims to determine the demographic and perinatal characteristics of premature infant according to head growth, identify clinical factors affecting growth catch-up, and explore differences in developmental outcomes according to catch-up states.th percentile and a no catch-up (NCU) group with a head circumference below the 10th percentile at 18–24 months of corrected age (CA).This nationwide prospective cohort study of Korean Neonatal Network data analyzed premature infants with very low birth weight  between 2014 and 2017. A total of 253 eligible infants who had completed the Bayley Scales of Infant and Toddler Development, Third Edition, were assigned into two groups: a catch-up (CU) group with a head circumference above the 10P < 0.05). On multiple linear regression analysis, BPD status was the most influential clinical factor affecting catch-up head growth after adjusting for gestational age, birth weight, and birth head circumference . At 18–24 months of CA, the NCU group exhibited lower developmental indices and a higher rate of developmental delay than the CU group. Motor developmental delay was the most significant factor relevant to catch-up head growth, and the motor development difference between the two groups was only statistically significant after adjusting for four major neonatal morbidities: IVH, BPD, sepsis, and NEC status .Most  premature infants exhibited catch-up growth at 18–24 months of CA. Rates of microcephaly, intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), sepsis, necrotizing enterocolitis (NEC), length of NICU stay, ventilation care, and parenteral nutrition were significantly greater in the NCU group (As association was observed between head growth catch-up status and developmental outcomes in VLBW infants at 18–24 months of CA. Key clinical factors associated with catch-up status included BPD and NEC status, length of parenteral nutrition, and ventilator care. Further study is needed to establish causality and explore additional factors that may influence developmental outcomes in this population. Recent advances in neonatal and neonatal intensive care have improved infant survival rates. In Korea, the survival rate of very low birth weight (VLBW) infants has also increased from 34% in the 1960s to 77.5% in the 2000s [Of 8,945 VLBW infants born between January 2014 and November 2017 and registered in the database registry of KNN, 318 with completed Bayley scales of infant and toddler development (BSID) III at 18–24 months of corrected age (CA) were selected for this study. The BSID test was revised and reconstructed into the third edition, which included a separation of the mental developmental index into language scale. A total 65 infants were excluded due to gestational age (GA) > 32 weeks (42 infants), the presence of major congenital anomalies (8 infants), non-Korean (3 infants) parents, and the presence of post intraventricular hemorrhage (IVH) hydrocephalus (12 infants)  group whose head circumference was below the 10thpercentile at 18–24 month of CA. A cutoff was used because previous researches showed the impact of head growth degree and velocity on neurodevelopmental outcomes [Three growth parameters  were analyzed for a specific period of time, including at birth, at discharge from the neonatal intensive care unit (NICU), and at 18–24 months of CA. Patients were divided into two groups according to their head circumferences. The first group was the catch-up (CU) group whose head circumference was above the 10outcomes –9.Four major factors were compared: 1) demographic factors ; 2) maternal factors ; 3) neonatal morbidity related factors ; and 4) environmental factors . Multiple linear regression was employed to determine factors affecting the status of catch-up in head growth. Factors showing statistically significant difference between the two groups were selected and entered into a logistic regression model. When a correlation between clinical factor and catch-up status was found, the adjusted odds ratio was used to offset the impact of extremely early preterm, SGA, and microcephaly instead of the crude odds ratio. These correlations are expressed as an odds ratio with a 95% confidence interval (CI), with a value greater than one indicating increased odds of not achieving catch-up after adjusting for GA, birth weight, and birth head circumference. When comparing developmental outcomes between the two groups, the adjusted odds ratio was used after adjusting for four major neonatal morbidities: IVH, BPD, sepsis, and NEC status. A P-value < 0.05 indicated statistical significance. All statistical analyses were performed using SPSS software ver. 26.0 .Demographic and perinatal characteristics, head circumferences, and language test results were subjected to frequency analysis. Data are described as median (maximum-minimum) for continuous variables and as numbers for binary and categorical variables. The independent t test and chi square test were used to compare demographic and perinatal characteristics, language developmental results, and clinical characteristics between the CU and NCU groups (P < 0.001). Among the three parameters, head circumference showed the biggest difference between the two groups, decreasing from birth to discharge. However, it increased from discharge to 18–24 months of CA   vs. 31.6% (65/206), P = 0.005; BPD: 68.1% (32/47) vs. 30.6% (63/206), P < 0.001; sepsis: 31.9% (15/47) vs. 17.0% (35/206), P = 0.021; NEC: 17.0% (8/47) vs. 3.9% (8/206), P < 0.001; NICU stay: 90.6 vs. 74.3, P = 0.002; ventilator care: 27.4 vs. 11.9, P < 0.001; parenteral nutrition: 40.6 vs. 25.6, P < 0.001). Birth weight (BW), rate of low maternal education, and rate of nursery use were significantly lower in the NCU group  vs. 19.4% (40/206), P = 0.032; nursery use: 21.3% (10/47) vs. 37.9% (78/206), P = 0.031).The demographic and perinatal characteristics of VLBW infants according to catch-up status are shown in Table ) , only IVH, BPD, sepsis, NEC status, length of ventilator care, and parenteral nutrition were significantly associated with catch-up status. BPD status was the most significant clinical factor affecting catch-up head growth  Table .Table 3C–24 months of CA, the NCU group exhibited lower developmental indices and higher rate of developmental delay than the CU group . Motor developmental delay was the most significantly relevant factor associated with catch-up head growth. The motor development index difference between the two groups was only statistically significant after adjusting for four major neonatal morbidities: IVH, BPD, sepsis and NEC status   of infants exhibited no catch-up head growth at 18–24 months of CA. The developmental outcome depended on the catch-up status at 18–24 months of CA.This study analyzed 253 VLBW infants with birth weight under 1,500 g at a gestation age of 23 weeks to 31 weeks. The results demonstrated that the degree of head circumference, especially that during 18Head circumference is a valid indicator of total brain volume and it can be used as a proxy for brain growth. Measurement of postnatal head growth as determined by the change in head circumference has been associated with total brain tissue volume and neurodevelopmental outcomes including cognition. It has been reported that severe postnatal growth failure among VLBW infants is markedly influenced by intra uterine growth and major morbidities –5.In this study, the key perinatal factor determining catch-up status was the BPD. The pathophysiology that leads to infants with BPD having greater developmental delay is probably multifactorial, including chronic intermittent hypoxia, growth deficiencies, and altered environmental stimulation. First, central nervous system pathology in infants with BPD shows brain atrophy and gliosis compatible with chronic hypoxia. Second, recurrent oxygen desaturations in infants with BPD have been associated with poor weight gain which may give credence to the possibility of poor central nervous system growth. Third, environmental factors such as those associated with rehospitalization during the first year of life and feeding problems might ultimately affect mental development –20.–24 month of CA, especially in the motor developmental index. Several studies have documented significant deleterious effects for VLBW infants with head growth failure on motor outcome, showing early impairments specifically involving eye-hand coordination and postural balance [In this study, the NCU group exhibited lower developmental indices and a higher rate of developmental delay than the CU group at 18 balance , 22. TheJeng et al. (2008) have reported that the severity of BPD has a significantly negative linear relationship with motor developmental outcome in infancy after controlling for other risk factors . Keunen –24 months of CA with developmental outcome using brain magnetic resonance imaging.VLBW infants might have less prominent, more diffuse cerebral white matter injuries that are undetectable by ultrasound but which can cause developmental disorders. The diffusion-weighted magnetic resonance imaging technique provides exquisite soft tissue differentiation. Therefore, a further study is needed to investigate the association of head circumference at 18The strength of this study was that it included a prospective nationwide population-based cohort of VLBWI infants and used a newly revised developmental scale, BSID-III. This is a valuable aspect for analyzing various factors sequentially, including perinatal and postnatal factors. The results showed that developmental outcomes were significantly different between the CU and NCU groups.This study has some limitations. Developmental outcomes result from various factors combined, making it difficult to affirm that catch-up head growth is the sole decisive cause of developmental delay. Additionally, although the standard guidelines for measuring head circumference were followed, and steps were taken to minimize intra-observer and inter-observer errors by having trained nurses perform repeated measurements, the potential for human error in the measurement process cannot be entirely ruled out, as head circumference measurements can be subjective and may vary if not consistently conducted by the same person.–24 months of CA depended on whether head growth was caught up. Key clinical factors affecting the catch-up head growth were BPD, NEC status, length of parenteral nutrition, and ventilator care. These results showed the importance of head circumference measurement at 18–24 months of CA. Since infant developmental outcomes can predict school-age academic functioning, our results suggest that close follow-up and early intensive interventions are needed for VLBW infants with catch-up growth failure. Further research is needed to establish causality and explore additional factors that may influence developmental outcomes in this population.In conclusion, the developmental level of a VLBW infant at 18


In this study, we examined how age impacts the outcomes of breast cancer by comparing three age groups: patients 45 years old or younger, patients between 46 and 69 years old, and patients 70 years old or older. Despite similar cancer staging and tumor characteristics among the age groups, the study found that older patients were prone to suboptimal treatment. Older patients also had a lower overall survival rate, but this was not related to cancer itself. Instead, we found that undertreatment was a factor that negatively impacted survival for older women with breast cancer. This study suggests that tumor characteristics and treatment compliance are more important predictors of survival than chronological age.Age as a breast cancer (BC) prognostic factor remains debatable. Several studies have investigated clinicopathological features at different ages, but few make an age group direct comparison. The European Society of Breast Cancer Specialists quality indicators (EUSOMA-QIs) allow a standardized quality assurance of BC diagnosis, treatment, and follow-up. Our objective was to compare clinicopathological features, compliance to EUSOMA-QIs and BC outcomes in three age groups . Data from 1580 patients with staged 0–IV BC from 2015 to 2019 were analyzed. The minimum standard and desirable target on 19 mandatory and 7 recommended QIs were studied. The 5-year relapse rate, overall survival (OS), and BC-specific survival (BCSS) were also evaluated. No meaningful differences in TNM staging and molecular subtyping classification between age groups were found. On the contrary, disparities in QIs compliance were observed: 73.1% in ≤45 years and 46–69 years women vs. 54% in older patients. No differences in loco-regional or distant progression were observed between age groups. Nevertheless, lower OS was found in older patients due to concurrent non-oncological causes. After survival curves adjustment, we underscored evidence of undertreatment impacting BCSS in ≥70 years women. Despite a unique exception—more invasive G3 tumors in younger patients—no age-specific differences in BC biology impacting outcome were found. Although increased noncompliance in older women, no outcome correlation was observed with QIs noncompliance in any age group. Clinicopathological features and differences in multimodal treatment  are predictors of lower BCSS. Age as a prognostic factor in breast cancer (BC) remains debatable due to the lack of standardized comparative studies on the impact of multimodal treatment on age groups ,3,4,5,6.Irrespective of age, a guiding principle of BC treatment is to consider patients’ BC cure probability to minimize a preventable cause of death . SurvivaThe European Society of Breast Cancer Specialists (EUSOMA) certification process includes a set of quality indicators (QIs) that certified breast units should follow, enabling a standardized audit of BC diagnosis, treatment, and follow-up ,16,17,18The current aging population and the socioeconomic impact of the associated higher cancer incidence strengthens the ethical commitment and clinical challenge of treating older women with BC through well-supported evidence . DespiteThis single-center study was based on the patient cohort at the Breast Center of S. João University Hospital (BC-CHUSJ), certified by EUSOMA since 2017. The aims were to compare clinicopathological features, compliance to EUSOMA QIs and related survival outcomes in three pre-specified age groups  from 2015 to 2019.A benchmarking audit with international standards is an ethical imperative to strive for good clinical care ,17,18,20This observational study sought to contribute to answering the age-specific issue raised in a previous study whether the poorer outcome in older patients results from a minimalist therapeutic attitude, noted by lower QIs compliance, or whether it results from tumor (and patient) characteristics that are difficult to compare . We analAll patients with a newly diagnosed in-situ or invasive BC for 5 years (2015–2019) were included. Age groups were categorized as ≤45 years, 46–69 years, and ≥70 years according to the epidemiological profile of the population-based screening in Portugal. Patients with recurrent disease or patients who had only partial treatment at our center were excluded.The primary outcome was to evaluate the impact of clinicopathological features and compliance to EUSOMA QIs on survival by age group. We retrospectively analyzed anonymized data from our patients in the eusomaDB. Hospital ethics committee approval to prospectively collect patients’ data in the eusomaDB was obtained (CES 93-16). The clinicopathological and immunohistochemistry (IHC) features were recorded according to EUSOMA standards. No gene expression studies for therapeutic decisions were considered.The QIs were selected from the latest 2017 update of the EUSOMA working group . From thAs QIs for outcome measurements are lacking, we also analyzed the relapse rate, overall survival (OS), and BC-specific survival (BCSS). Patients were followed up until 31 December 2020. The median follow-up was 2.57 years .survminer (version 0.4.9) and survival (version 3.2.13) packages, using R language (v.4.1.2) [p-values < 0.05 were considered statistically significant.QIs were computed for each age group using a proportional test to assess the QI performance. For continuous variables, normality was assessed by visual inspection of the data distribution, supported by QQ-plot analysis. If normally distributed, the results were summarized by the mean and standard deviation; otherwise, the median and interquartile range were described. Absolute (number) and relative (%) frequencies were reported for categorical variables. The Pearson χ2 test and Fisher’s exact tests were used to assess the differences between the independent categorical variables across the pre-defined groups. The Kruskal–Wallis rank-sum test was used to evaluate statistically significant differences between the medians of the three age groups. Survival analyses were performed using Cox proportional hazards models and the Kaplan–Meier method. A competitive risk analysis was performed to untangle BC from all-cause mortality. Internal validation was performed using bootstrap to assess the Cox models’ robustness regarding the events . In brief, the models were run 1000 times with replacement (with event stratification), and the concordance index was gauged. All statistical analyses were performed using the v.4.1.2) . p-valuePatient characteristics are described in No meaningful difference was observed in the proportions of 0–III TNM stages between age groups. There was a lower prevalence of stage IV at diagnosis in the youngest women (1.0% in ≤45 years versus 3.6% in 46–69 years and 3.5% in ≥70 years). Invasive grade 3 (G3) tumors were significantly more in ≤45 years women (53.3%) than in 46–69 years (35.1%) or ≥70 years (26.0%) women. The proliferation activity index (Ki67) was selectively studied in invasive G2 tumors; however, it was not performed in most cases, namely in 86.0% of older women. The proportion of luminal tumors was identical, apart from a lower prevalence of luminal-B tumors in ≥70 years women (15.0% in ≤45 years versus 8.0% in ≥70 years), as well as the triple negative (TN) tumors distribution. Concerning HER2 overexpression, we found a significant difference between age groups: 21.0% in ≤45 years, 16.0% in 46–69 years, and 10.0% (and 5.8% not assessed) in ≥70 years women.Surgery, with a predominance of breast conservative surgery, was the first treatment option in all age groups. Most significant was the difference in the omission of surgery: 17.4% in older women, 3.0% in 46–69 years, and 0.6% in ≤45 years. The proportion of younger women who began their treatment with neoadjuvant chemotherapy (37.4%) was identical to that of older women who started with endocrine therapy (32.3%). Adjuvant chemotherapy or radiotherapy was significantly less undertaken in older patients .To emphasize the The QIs compliance is given in The QIs compliance was 73.1% in the youngest and 46–69 years women, and 54.0% in the older patients. In the ≤45 years group, we attained the desired target in 11 of 19 mandatory QIs and 2 of 7 recommended QIs. The minimum standard was reached additionally in 3 mandatory QIs and 3 recommended QIs. In the 46–69 years group, the desirable target was achieved in 13 mandatory QIs and in 2 recommended QIs and the minimum standard was reached in 4 QIs (1 mandatory and 3 recommended QIs). In the ≥70 years group, we reached the desired target in 8 obligatory QIs and 2 recommended QIs and the minimum standard in another 3 mandatory QIs and 1 recommended QI.The 5-year loco-regional relapse showed no disparities between age groups. The same was found for distant progression with no significant difference in the distribution of sites of metastatic disease between younger or older patients . We obseChronological age should not be a determinant of BC prognosis or treatment ,25. ThisAlthough several studies have investigated clinicopathological features at different ages, few made an age group direct comparison ,34,35,36International guidelines, such as the EUSOMA QIs, should be regarded as recommendations for excellence in clinical care ,16,17,18As in the previously cited study devoted to the variation in compliance to EUSOMA QIs by age , we notep = 0.698), but evidence of undertreatment impacting survival: surgery  and adjuvant radiotherapy  allow a reduction of BC-specific mortality risk. Furthermore, an analysis of the competing risks [Without irrefutable evidence ,33,34,35ng risks  showed tFinally, Cox model robustness was assessed using bootstrapping with replacement. One thousand runs were performed for each event , and the concordance index (C-index over 0.8) suggests robust models for both events .Our study sought to contribute to demystifying the common misconception of age-specific differences in BC biology impacting outcomes, which we did not observe in daily practice. Despite a unique exception—a higher prevalence of invasive G3 tumors in ≤45 years patients—a more aggressive biology was not observed at younger ages nor the contrary in older women. Although there was increased noncompliance in older women, no outcome correlation was observed with QIs noncompliance in any age group.Chronological age should not be considered a prognostic factor in BC, as clinicopathological features and multimodal treatment differences are the main predictors of lower BCSS in older patients. For this age subgroup, earlier diagnosis, and personalized treatment—supported not by a frailty demand  but by a multidimensional geriatric assessment to pursue biological age and socio-family circumstance—are demanded.


This review aimed to determine what methods are used to assess nutritional status, the levels of nutritional status, determinants of undernutrition, and nutritional interventions employed for adolescents with HIV on Anti-Retroviral Therapy follow-up in Low- and Middle-Income countries.Established methods were used to systematically identify and retrieve studies published in five databases between January 2000 to May 2021, and citation searching. Quality was appraised and findings were synthesized using narrative analysis and meta-analysis.Body Mass Index is the major indicator of nutritional status. The pooled prevalence of stunting, wasting, and overweight were 28.0%, 17.0%, and 5.0%, respectively. Adolescent males are 1.85 and 2.55 times more likely than adolescent females to suffer from both stunting and wasting at AOR = 1.85  and AOR = 2.55 , respectively. Similarly, adolescents with a history of opportunistic infections were 2.97 times more likely to be stunted than uninfected adolescents, AOR = 2.97 . One single intervention study found significant improvements in anthropometric status after nutritional supplementation.The few studies that have been conducted on nutritional status in adolescents living with HIV in low- and middle-income countries indicate that stunting and wasting are common in this population. Avoiding opportunistic infections is an important protective factor but the review highlighted the generally inadequate and fragmented nature of nutritional screening and support programs. Development of comprehensive and integrated systems for nutritional assessment and intervention services during ART follow-up should be prioritized to improve adolescent clinical outcomes and survival.The online version contains supplementary material available at 10.1186/s40795-023-00714-z. Adolescence (ages 10 to 19 years . This agAdolescents are disproportionately affected by the human immunodeficiency virus (HIV) , 3. In 2Adolescents living with HIV are vulnerable to undernutrition due to their elevated nutritional needs imposed by a puberty growth spurt and HIV infection. Malnutrition is a major threat to the health of HIV-infected individuals and is associated with increased risks of morbidity and mortality . DespiteIn many LMICs, the targets for adolescents’ physical health predominantly focuses on the sexual and reproductive health (SRH) behaviors of young people aged over 15. However, nutrition plays a critical role not just for SRH but also in the life cycle, transitioning from adolescence to healthy adults. Malnutrition among children and adolescents is associated with delayed growth, impaired cognitive maturation, lower intellectual quotient, behavioral problems and increased risk of contracting communicable disease , 10. FurAn integrative review design was used as it was anticipated that evidence would derive from a variety of quantitative and qualitative studies.The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline was followed to report results  see Sup.What methods are used to assess nutritional status of adolescents who are HIV positive on ART follow-up living in LMICs?What is the nutritional status of adolescents who are HIV positive on ART follow-up living in LMICs?What are the determinant factors associated with the nutritional status of adolescents who are HIV positive and on ART follow-up living in LMICs?What nutritional interventions, if any, have a significant improvement on the nutritional status of adolescents who are HIV positive and on ART follow-up living in LMICs?malnutrition and nutritional status were combined with synonyms of screening and assessment ” and “Population, Exposure, Outcomes (PEO)” frameworks were used to develop robust literature search strategies. After a preliminary assessment of the appropriate Medical Subject Heading terms (Title-Abstract-Keywords), keywords and synonyms, a search strategy was developed. As the terms nutrition screening and assessment were often used interchangeably in studies, synonyms of The PICO/PEO framework was applied for research question 1 & 2 as follows:◦In adolescents who are HIV positive and on ART follow-up living in LMICs (P), what methods of assessment were used (I) to determine the level of nutritional status (O) compared with WHO standards (C)?◦In adolescents who are HIV positive on ART follow-up living in LMICs (P), what levels of nutritional status (O) were reported compared with WHO standards (C)?To address research question 3:◦In adolescents who are HIV positive and on ART follow-up living in LMICs (P), what determinant factors (I or E) lead to a changed (increased/decreased) risk of malnutrition/undernutrition (O)?To address research question 4 effectiveness studies were sought to determine:◦What nutritional interventions (I) affect the nutritional status outcomes (O) of adolescents who are HIV positive on ART follow-up living in LMICs (P) compared to comparison group (C) outcomes?The search strategy was applied, with individual modifications, to the electronic databases: Medline (Ovid), PubMed, ProQuest, EMBASE (Ovid), and Cochrane Library of Databases. Records were systematically searched for publications from January 2000 to May 2021 for materials that met the inclusion criteria. In addition, citations/reference lists of retrieved relevant articles were searched. Additional articles were advance-searched from Web of Science and Google Scholar.Studies conducted in LMICs, classified according to the World Bank criteria , 14Aged between 10—19 years of age, orIf age was not specified, participants were referred to as older children OR young adults OR teenagers OR young person’s OR young people whose age was 10 – 24 years, orIf the sample was of mixed age (children/ adolescent/ young adult) the mean or median age or most of the sample (> 50%) must lie between 10–19 yearsThe target population was adolescents who were HIV positive and on ART follow-up. For this review, participants were required to be specified as:Primary studies, both published and grey literature in the English languageTo address the first three questions, prospective studies, retrospective studies, cross-sectional studies, descriptive/quantitative and experimental studies, qualitative studies, and mixed-methods studies were soughtTo address the fourth question effectiveness designs, such as experimental studies, randomized controlled trials (RCT), controlled clinical trials, quasi-experimental studies, or other interventional study designs were required.Conference abstracts and other studies which did not have the full text availableReviews and other forms of report using secondary analysis.The results of the search were exported to an Endnote library Version 20 after which duplicate items were automatically eliminated. Article titles, abstracts, and keywords were reviewed by two independent reviewers (MG & AK) for evaluation against the inclusion and exclusion criteria for eligibility. The complete texts of all potentially relevant papers were retrieved, and their citations were uploaded to the Joanna Briggs Institute System for the Unified Management, Assessment, and Review of Information (JBI SUMARI) for full-text screening . For articles that did not have full details, authors were contacted to obtain the full-text report at the corresponding author addresses. Papers were retained for full-text evaluation in cases where eligibility was ambiguous. Studies that were ineligible were excluded, with reasons noted. At each level of the selection process, any discrepancies between the reviewers were settled through conversation or by consulting a third reviewer . The outcomes of the search and screening procedure were displayed in a PRISMA flow diagram Fig. .Fig. 1PrData were extracted by MG, AK, and AC/MC, and verified by LP and XX. Two reviewers extracted data for the quantitative component from the quantitative and mixed methods (quantitative component only) studies related to study contexts and participants, research techniques, interventions, and outcomes relevant to review questions. Data were taken verbatim where possible and any discrepancies between the reviewers were settled through conversation or by consulting a third reviewer. When necessary, data were requested from the study authors.The selected studies were critically evaluated by two independent reviewers for methodological quality using the JBI appraisal instruments , 16. RevExtracted data were exported from Microsoft Excel to STATA Version 17.0 (software) for analysis. The characteristics of included studies and descriptive results were presented using tables and graphs. A random effects meta-analysis model was used and the pooled effect size was employed. Forest plots were used to show the pooled estimates with 95% confidence intervals (CI). The strategy for meta-analysis was based on the guidance of the Campbell systematic review model  to deterAfter duplicates were removed, a total of 1568 articles remained for Title-Abstract screening. Of these, 1347 articles were excluded as they did not meet inclusion criteria, and 221 articles remained for full-text screening. Of these 221 articles, 27 were removed because the full report was not available and 177 were excluded for not meeting the inclusion criteria. In total, 17 articles were retained for data extraction and synthesis  were cross-sectional studies [n = 6, 35.3%) comprised: observational studies (n = 3) [n = 1) [n = 1) [These 17 primary articles recruited a total of 2873 study participants in LMICs. The majority of articles  ; case–co [n = 1) ); mixed- [n = 1) , and one [n = 1)   took place in upper-middle income countries [n = 5, 29.4%) [Studies were conducted in seven LMIC countries in South American, Asian and African continents. The majority  , 33 and , 29.4%) –25, 35 n = 7, 4.2% took n = 13, 76.5%) used BMI as an indicator of nutritional status, followed by height for age . Six (35.3%) studies assessed dietary intakes and estimated energy and nutrient intakes, and three studies (17.6%) assessed body fat composition using standardized fat measurement  reported nutritional status in terms of stunting and wasting; six studies  reported on overweight status. In most studies BMI-for-age Z-score and Height-for-Age Z-score (HAZ) below -2 Z score were used to determine nutritional status  but a few articles used Weight-for-Age Z-score (WAZ) and Weight-for-Height Z-scores (WHZ) below − 2 Z- scores (WHO standard).The majority of studies . The highest prevalence of stunting, at 46.6%, was reported from a study in Cambodia [Most studies that reported stunting demonstrated that it occurred in between one fifth and one third of the participants . The highest prevalence of wasting was reported in a study conducted in Ethiopia (60.2%) [More than half the studies reported wasting in between one tenth and one fourth of the samples ( (60.2%) , and the (60.2%)  . The highest (15.6%) and lowest (1.9%) prevalence of overweight were reported from studies conducted in Brazil [Most of the studies demonstrated that overweight was the least common findings of nutritional assessment  [2 = 31.9%, P = 0.225) [A total of 1261 participants were included to analyze the association between sex and stunting among adolescents living with HIV in LMIC. The pooled odds ratio showed that male adolescents were 1.847 times at greater odds of stunting than their female counterparts , I= 0.026) , 25, 35.= 0.225) , 35  [A total of 1354 participants were included to analyze the association between sex and wasting among adolescents living with HIV in LMIC. The pooled odds ratio showed that male adolescents were 2.55 times more likely to become wasted / thin compared to their female counterparts , I= 0.215) , 26, 35 Only one interventional study was found, trialling nutritional supplementation of 360 kcal energy and 32.2gm protein in food made from Peanut Chikki and another source. The study reported that after one year of supplementation on a daily basis the study participants showed a significant improvement in their Height-for-Age, Weight-for-Age and BMI-for-Age indices .2 = 92.89%, p < 0.01), , , Fig. .Fig. 3Fo2 = 0.00, p = 0.6), , Fig. .Fig. 4FoSubgroup analysis was performed using country and study design to identify the source of heterogeneity.2 = 82.47%, P < 0.001) and the lowest was in Brazil, at 17.40% .Subgroup analyses were conducted by country for Brazil , 30, 34 2 = 89.58, P < 0.001) [Sub-group analysis was also conducted by study design for cross-sectional studies, and the pooled prevalence estimates of stunting by this design was 30.03%  , 34  [2 = 88.87, P < 0.001) [2 statistics, the Cochran’s’Q’ result and p-values, as indicated in Table Furthermore, sub-group analysis was conducted by study population, and the pooled prevalence estimate of stunting for only adolescent age study population was 32.0%  –25, 31, < 0.001) , 30, 34.2 = 88.37%, P < 0.001).Subgroup analyses were conducted by country for Brazil , 30, 34,2 = 98.66, P < 0.01) [Sub-group analysis was also conducted by study design for cross-sectional studies, and the pooled prevalence estimates of wasting by this design was 19.3% ((95% CI: 7.0–31.60), I < 0.01) , 34, 35 2 = 86.34, p < 0.0001) [2 = 98.96, P < 0.0001) [Furthermore, sub-group analysis was conducted by study population, and the pooled prevalence estimate of wasting for only adolescent age study population was 15.6%  –25, wher 0.0001) , 34, 35.2 statistics, Cochran’s’Q’ results and the p-values indicated in Table Regarding the tests of differences within each subgroup analysis, there was evidence of significant heterogeneity observed within each sub-group based on the statistical significance of IThe average JBI quality score of included studies was 6.76 ; the minimum quality score was 5 and maximum was 10 . A score of 7 and above was described as indicative of good quality, and 10 (58.8%) of the articles scored at this level  if underlying malnutrition is not also addressed . Whilst This review revealed the narrow variety of nutritional assessment techniques in use with adolescents with HIV on ART. Most studies used anthropometric assessments, most commonly BMI-for-Age (76.5%) and Height-for-Age (41.2%). These anthropometric tools are inexpensive, portable, simple to use, and require minimal training, but are less sensitive and specific indicators of nutritional status. A few studies (17.6%) also conducted body fat composition measurements, using various standardized tools, such as skin-fold thickness, circumference measurement (Waist/hip circumference), Bioelectrical Impendence Analysis (BIA), Dual-energy X-ray Absorptiometry and Air Displacement Plethysmography (ADP) , 22, 27.n = 4), FFQ (n = 1) and individual assessment of dietary diversity (n = 1) to identify energy and nutrient intake. There are significant challenges in obtaining accurate diet histories as the tools are arduous to complete and of little value unless there is a high degree of completeness and accuracy. Use of such limited methods in the determination of nutritional status results in limited information and difficulty in differentiating whether apparent undernutrition was a result of disease effects, inadequate food intake or other predisposing factors.Some studies (35.3%) evaluated dietary intake, using one-time 24-h dietary review  .Six of these seventeen studies revealed the prevalence of overweight, with the pooled prevalence of 5.0% and the highest and lowest frequencies reversing the findings for wasting. A study in Brazil found the highest frequency of overweight young people (15.6%), with Ethiopia providing the lowest prevalence (1.9%) . This vaRegarding factors associated with undernutrition, male sex predisposed to both stunting and wasting, occurring at 1.85 and 2.55 times higher than for their female adolescent counterparts, respectively. This might be a consequence of the generally greater growth spurt and energy requirements of male compared to female adolescents , 39. It Adolescent nutrition has been largely overlooked in intervention and policy research. Most intervention studies have focused on micronutrient supplementation, and few have considered multiple factors in adolescent nutrition . It may Sustainable nutrition care and support for adolescents with HIV are used to provide adequate nutrient intake to promote normal growth and development during puberty, maintain adequate nutritional status to promote health and prevent disease after physiological growth is complete, promote optimal nutrition and prevention of malnutrition, manage or reduce symptoms of HIV disease, enhance drug compliance and efficacy through diet counseling, prevent food-borne illness, and manage complications associated with HIV and antiretroviral therapy (ART) . IntegraThis assessment has many strengths. An extensive search strategy was implemented and data were analyzed using a rigorous methodology. Explicit inclusion and exclusion criteria related to population and comprehensive outcomes were assessed. Four authors were involved in the quality assessment. As the included studies showed considerable heterogeneity, we performed advanced statistical analysis such as meta-regression to identify possible sources of heterogeneity. Despite the above strengths, this review has some limitations that should be considered before interpreting the results. Since most of the primary studies included in this systematic review and meta-analysis are cross-sectional, no analyses could be undertaken to pool intervention effects as only one single eligible intervention study was found. In addition, the limited number of published studies from low-middle income countries that were retrieved and used for the pooled effect size, may have yielded underrepresentation of data from other low middle-income countries. Other limitations of this study included significant heterogeneity between the primary studies, with review methods limited to those published in the English language. This may have resulted in the exclusion of some essential studies.In conclusion, the review demonstrates the paucity of research on nutrition in adolescents living with HIV, and the effects of supplementation intervention could not be tested. The review results indicate a high prevalence of stunting and wasting in HIV-infected adolescents, but low proportions of overweight. Opportunistic infection was the sole factor shown by this review to be both significant and amenable to intervention. The inadequate and fragmented nutritional screening and support programs used by government and non-governmental organizations for this population in clinical settings were highlighted.Review findings have implications for improving the healthy living of adolescents infected with HIV in LMIC through acting on the demonstrated prevalence and identified determinants of undernutrition; by integrating rigorous nutritional screening and assessment modalities into routine services, and developing and evaluating nutritional interventions.Review findings indicate that comprehensive systems of nutritional assessment and intervention should be integrated within HIV services to be delivered during routine follow-up of adolescents in the ART clinic. Despite its limitations, review findings provide evidence that can be used by policy-makers, health planners and managers, researchers, and planners in LMICs to create an evidence-informed strategy supporting Sustainable Development Goal 1–3.Additional file 1: Supplementary Table 1. Search Strategy “Population, Intervention / Exposure, Comparator / Control, Outcomes (PICO or PEO) Framework”. Supplementary Table 2. Characteristics of studies included in this systematic review and meta-analysis, 2022. Supplementary Table 3. Distribution of included studies outcomes in this systematic review and metanalysis, 2022. Supplementary Table 4. Quality appraisal status of studies included according to JBI characteristics, 2022.


Cryptococcal meningitis (CM) is the most common fungal infection of the central nervous system that can cause significant morbidity and mortality. Although several prognostic factors have been identified, their clinical efficacy and use in combination to predict outcomes in immunocompetent patients with CM are not clear. Therefore, we aimed to determine the utility of those prognostic factors alone or in combination in predicting outcomes of immunocompetent patients with CM.The demographic and clinical data of patients with CM were collected and analyzed. The clinical outcome was graded by the Glasgow outcome scale (GOS) at discharge, and patients were divided into good (score of 5) and unfavorable (score of 1–4) outcome groups. Prognostic model was created and receiver-operating characteristic curve analyses were conducted.A total of 156 patients were included in our study. Patients with higher age at onset (p = 0.021), ventriculoperitoneal shunt placement (p = 0.010), Glasgow Coma Scale (GCS) score of less than 15(p< 0.001), lower CSF glucose concentration (p = 0.037) and immunocompromised condition (p = 0.002) tended to have worse outcomes. Logistic regression analysis was used to create a combined score which had a higher AUC (0.815) than those factors used alone for predicting outcome.Our study shows that a prediction model based on clinical characteristics had satisfactory accuracy in prognostic prediction. Early recognition of CM patients at risk of poor prognosis using this model would be helpful in providing timely management and therapy to improve outcomes and to identify individuals who warrant early follow-up and intervention.The online version contains supplementary material available at 10.1186/s12879-023-08337-2. Cryptococcal meningitis (CM) is the most common fungal infection of the central nervous system (CNS) . DespiteIn this study, we aimed to explore the clinical significance of those prognostic clinical signatures used alone or in combination in the prognostic prediction of patients with CM.We conducted a review of hospitalized patients with CM from January 2003 to August 2022.The diagnosis of CM was based on clinical features and positive laboratory findings. The patients with CM were included if they had to meet one or more of the following criteria: (1) positive culture of cryptococcus from CSF, (2) positive CSF india ink testing, (3) positive CSF cryptococcal antigen testing, or (4) positive cerebral biopsy. Patients who had one or more identifiable underlying diseases were categorized as immunocompromised hosts, this included individuals with a history of autoimmune disorders, long-term glucocorticoids or other immunosuppressive therapies, idiopathic CD4 T-cell lymphopenia, HIV infection, malignant tumor, hepatic cirrhosis, end-stage renal failure or diabetes , 7. MeanIn this retrospective study, we collected demographic data, major symptoms and signs, neuroimaging features, laboratory findings and clinical outcome at discharge. The clinical outcome was evaluated by a neurological physician using Glasgow Outcome Scale (GOS) within 24 h prior to discharge. Score of 1–4, indicating death, vegetative status, severe disability and moderate disability, was considered “unfavorable” clinical outcomes. Score of 5, indicating no or mild disability, was considered “good” outcome . The degMean and standard deviations were presented for parametric variables, while medians and quartiles were used for non-parametric variables. Chi squared and fisher’s exact tests, Two-sample t-test (parametric) or Mann Whitney U test(non-parametric) were used to assess differences in demographic and clinical features between the good and unfavorable outcome groups. Variable selection was performed using the least absolute shrinkage and selection operator (LASSO) regression model, followed by multivariable logistic regression analysis to create a combined score for predicting the outcome utilizing the independent variable statistically significant at the univariate analysis, in which P value levels for inclusion and exclusion criteria were set as 0.05 and 0.10, respectively. Odds ratio (OR) and its 95% Confidence interval (CI) were estimated for each factor. To determine clinical efficacy of individual variables and the combined predictive score. The pairwise comparison of ROC curves was conducted with Delong’s test. The area under the curve (AUC) with 95% CI that evaluates the sensitivity and specificity, and cut-off values were calculated. P values < 0.05 were considered statistically significant. All statistical analyses in this study were conducted using SPSS  and MedCalc Statistical Software .A total of 156 confirmed patients with CM  with complete data were included, and 49 of them were considered immunocompromised.In our study, the most frequent symptoms included headache (89.7%), fever (55.8%), vomiting 41.0%). Demographics and clinical manifestations of all cases in the training set are listed in Table .0%. Demo9/L. The median WBC count in the CSF was 54.0 106/L, the median CSF glucose concentration was 2.18  mmol/L. The median CSF chloride concentration was 117.6  mmol/L. The median CSF protein concentration was 0.87  g/L. The sensitivity of the CSF India ink test/antigen test and culture in our study were 82.1% and 48.1%, respectively. One patient was diagnosed with CM by positive cerebral biopsy. Laboratory data and features of neuroimaging were presented in Table 87.8% of patients (n = 137) had the highest GCS score of 15. The median white blood cell (WBC) count in the blood was 8.2  × 10p = 0.021), ventriculoperitoneal shunt placement (p = 0.010), GCS score of less than 15(p< 0.001), lower CSF glucose concentration (p = 0.037) and immunocompromised condition (p = 0.002) tended to have worse outcomes  with p-value of less than 0.1 in univariate analysis were included in LASSO, lambda.min and lambda.1se  were 0.013 and 0.074. Optimal lambda.min resulted in 8 nonzero coefficients  curve was performed to investigate the predictive value of those markers used alone and combined score. We found that CSF glucose concentration, GCS score of <15, age at onset , ventriculoperitoneal shunt placement , immunocompromised condition  and combined score had significant accuracy for predicting the unfavorable outcomes in patients with CM . Additionally, it could provide a helpful tool for risk assessment and decision-making in treatment strategy. Identifying patients with a higher risk of poor outcome could facilitate earlier, aggressive treatment  and potentially improve outcomes. Conversely, identifying patients with a lower risk of poor outcome could enable the use of moderate treatment to relieve the side effects and the financial burden caused by long-term antifungal therapy.There were some limitations on the strength of this study. A larger sample size may allow findings to be more accurate. Moreover, no data of long-term clinical outcome after discharge were recruited, the utility of the clinical factors here analyzed on predicting long term prognosis was unattainable in this study. Because the vast majority of patients have not undergone CrAg test, the finding of the CrAg test was not included in our study. Therefore, a multicenter study with long term follow-up data and more variables should be performed for a more detailed study.The present study established a prediction model based on clinical characteristics, which had statistically significant accuracy in prognostic prediction. Our findings may help clinicians early identify patients with poor outcomes and optimize treatment strategy.Below is the link to the electronic supplementary material.Supplementary Material 1


Zea mays L.) and cassava (Manihot esculenta Crantz). We determined the soil nutrient contents and physicochemical properties as well as the microbial communities by high-throughput sequencing. We found that the relay intercropping system changed the bacterial community structure, especially the rhizosphere microorganisms. The bacterial community was characterized by a higher abundance of the phyla Chloroflexi, Proteobacteria, and Actinobacteria and of the genus AD3, which are related to nutrient cycling and decreased bioavailability of Cd. At the same time, the relay intercropping system reduces the relative abundance of pathogenic bacteria and biomarkers of organic pollution. The relay intercropping systems significantly boosted soil pH and available K levels in addition to the monocropping yield. The results of this study suggest that maize/cassava relay intercropping, starting from the first year, not only provides a stable supply of food and income due to the diversified cropping systems but is also beneficial for the improvement of soil quality and the soil microbial community.The maize/cassava relay intercropping system can be a specific and efficient cropping pattern in a tropical/subtropical field. Relay intercropping systems contribute to the optimization of land use, fostering sustainable and efficient agriculture. This study entails a first-year comparative intercropping experiment using maize ( AlthougIntercropping has several advantages, including efficient nutrient acquisition, reduced soil-borne diseases, reduced use of herbicides and pesticides, and increased microbial diversity in the farmland soil–plant system . MechaniMaize has received attention in intercropping systems with legumes, pepper, peanut, alfalfa and other crops because of its positive effect on crop yield and nutrient use efficiency . Cassava2.2.1.−1 organic matter, 1.11 g kg−1 total N, 96.6 mg kg−1 available N, 217 mg kg−1 available P, and 46.0 mg kg−1 available K in the 0–20 cm soil layer.Experiments were conducted from 2020 to 2021 at an experimental farm in Guiping, Guangxi Province, China . The climate of the experimental site was subtropical monsoon. The main soil type is loam red soil, and the farming system is two crops a year. In dry land, the main crop is cassava, intercropping peanut, corn and other crops. The local farm area is approximately 100 hectares. The experiments were conducted in soil that had been cultivated with cassava and maize patterns for more than 10 years. Before the experiment, the soil had a pH of 4.10, 35.6 g kgThe maize/cassava relay intercropping system was used in the field experiments. The three treatments with three replications were as follows: (1) sole cassava: the intrarow and interrow spacing of cassava plants was 80 and 100 cm, respectively. (2) Cassava and maize intercrops: the intercropping patterns utilized two rows of maize and one row of cassava. The intrarow and interrow spacing of maize plants was 40 and 50 cm, respectively. While cassava was planted at the center point of four maize plants, the intrarow and interrow spacing of cassava plants was 80 and 100 cm, respectively. (3) Sole maize: the intrarow and interrow spacing of maize plants was 40 and 50 cm, respectively. The row spacings and spacing of cassava remained the same, and the row spacings and spacing of maize remained the same. Therefore, cassava/maize intercropping is equivalent to the superposition of cassava monoculture and maize monoculture.2 (4 m × 8 m), including four-strip cassava or eight-strip maize or four-strip cassava and eight-strip maize , total nitrogen (TN), alkali-hydrolysable nitrogen , available phosphorus (AP), and available potassium (AK). The concentration of soil nutrients was measured following the protocols described below. The soil pH was determined at a 1:5 solid to liquid ratio (w to v) using deionized water (METTLER FE28). The SOM content was measured using vitriol acid-potassium dichromate oxidation . The TN 4F . AK was traction . Microbitraction . We calc2.3.2.3.1.−1 with sterile water.Total genomic DNA from the soil samples was extracted using the CTAB method. The DNA concentration and purity were determined on 1% agarose gels. After quantification, DNA was diluted to 1 ng μl2.3.2.The V4 region of the 16S rRNA genes of bacteria was amplified using the forward primer 515F (GTGCCAGCMGCCGCGGTAA) and reverse primer 806R (GGACTACHVGGGTWTCTAAT) with barcodes. The ITS region of fungal genes was amplified using the forward primer ITS1F (CTTGGTCATTTAGAGGAAGTAA) and reverse primer ITS2R (GCTGCGTTCTTCATCGATGC). PCR was carried out in a 30 μl volume: 15 μl of Phusion® High-Fidelity PCR Master Mix (New England Biolabs), 0.2 μM of both forward and reverse primers, and 10 ng DNA. PCR cycles were completed in a BIO-RAD T100™ Thermal Cycler (USA) at 98°C for 1 min, followed by 30 cycles of denaturation at 98°C for 10 s, annealing at 50°C for 30 s, elongation at 72°C for 30 s, and finally 72°C for 5 min. PCR products were purified by electrophoresis on a 2% agarose gel. Then, the purified PCR products were quantified using a Qubit 2.0 Fluorometer (Thermo Scientific). Equivalent PCR products of different samples were mixed together and purified with a GeneJET Gel Extraction Kit (Thermo Scientific).2.3.3.Sequencing libraries were generated using an Illumina TruSeq DNA PCR-Free Library Preparation Kit . The library was qualified using a Qubit 2.0 Fluorometer (Thermo Scientific) and Agilent Bioanalyzer 2100 system. Finally, the library was sequenced on an Illumina HiSeq 2500 platform.2.4.p < 0.05. All statistical analyses were carried out using SPSS (version 22.0). Alpha-diversity , Comparison of bacterial community composition between rhizosphere soil and non-rhizosphere soil in different cropping systems was performed through the analysis of the β diversity of the soil microbial community. Principal coordinate analysis (PCoA), redundancy analysis (RDA)/canonical correlation analysis (CCA), variation partitioning analysis (VPA), correlation analysis and figures were performed using the free online Majorbio Cloud Platform.One-way analysis of variance (ANOVA), t test and non-parametric tests were performed to determine the difference between treatments, and the significance was set at 3.3.1.Compared with the initial soil, planting crops reduced the soil pH. The pH of both rhizosphere and non-rhizosphere soil was lower than that of the original soil. The rhizosphere soil pH was lower than that of the non-rhizosphere soil. Cassava and maize relay intercropping can slow the decrease in soil pH. The decrease in soil pH in the cassava and corn monocropping soil was larger, while the decrease in soil pH in the cassava and corn intercropping soil was smaller. Planting increased soil organic matter and available potassium in rhizosphere and non-rhizosphere soil. Rhizosphere soil has a higher content of organic matter and available potassium than non-rhizosphere soil. The increase in non-rhizosphere soil organic matter in monoculture cassava was the largest, followed by maize, and the increase in non-rhizosphere soil organic matter in intercropped cassava and maize was the smallest. The available K content of maize non-rhizosphere soil was higher than that of cassava, and the available K content of intercropped maize non-rhizosphere soil was significantly higher than that of other treatments.3.2.After filtering, 203, 6,588 reads were obtained, and 52,171 operational taxonomic units (OTUs) were identified with 97% similarity for the bacterial community. The alpha diversity  of the planting patterns was not significantly different . HoweverPrincipal coordinate analysis (PCoA) was used to study the similarity or difference in sample community composition. Bacterial community structures were distinctly grouped by planting pattern on a PCoA plot . In addi3.3.The relative abundance of bacteria at the phylum level and genus level for different planting patterns is shown in AD3, Subgroup_2, Acidothermus, and TK10. The relative abundance of AD3 in each treatment, as the main genus in our experiments, accounted for a large proportion, and the lowest proportion was more than 19%. In different monocropping/intercropping treatments, the order of relative abundance of AD3 was CR > MR > CM_CR > CM_MR. The relative abundance of Subgroup_2 showed an increasing trend in cassava crops, and this increase was independent of intercropping.The most abundant genera in the different cropping systems were Candidatus_Staskawiczbacteria, and 3 genera in cassava rhizosphere soil in the maize/cassava relay intercropping system (CM_CR), Promicromonospora, CCD24, and Pseudorhodoplanes. It further revealed one genus in cassava monoculture rhizosphere soil (CR), Rudaea  revealed one genus in cassava non-rhizosphere soil in the maize/cassava relay intercropping system (CM_CN), , Rudaea , and one3.4.Redundancy analysis (RDA) can explain the relationship between environmental factors and the soil microbial community well. As shown in 4.Increased crop yield as well as improved nutrient use efficiency are considered advantages of intercropping as an eco-friendly system . In our Compared with the original soil, the organic matter of the non-rhizosphere and rhizosphere in each treatment was significantly improved, and the organic matter content of monocropping was higher. For non-rhizosphere soil organic matter content, it increases in cassava was higher than that in maize. The non-rhizosphere soil organic matter of cassava decreased by 18.4% in intercropping compared with that of monoculture, while that of maize decreased by 8.7% . GiagnonAs for the impact of intercropping on organic matter content, 2 in the soil solution and by the H+ and OH− ions released by roots to balance the charge upon uptake of anionic nutrients  was higher in cassava monocropping treatments, its relative abundance was correlated with that of other pathogenic bacteria  can be found at: Sequence Read Archive, accession number: SRP410378.CH: resources and writing – original draft. BZ: conceptualization, writing – reviewing, and funding acquisition. HW: methodology, investigation, and funding acquisition. YW: writing – reviewing. JH: conceptualization, project administration, and funding acquisition. All authors contributed to the article and approved the submitted version.This work was supported by the National Key R & D Program of China (2020YFD1000603), China Agriculture Research System (CARS-11-HNHJ), Project funded by China Postdoctoral Science Foundation (2021M692144) and Shanghai Post-doctoral Excellence Program (2021304).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


To retrospectively compare the clinical and radiological outcomes of staged lateral lumbar interbody fusion (LLIF) combined with posterior instrumented fusion(PIF)with PIF alone for the treatment of adult degenerative lumbar scoliosis (ADLS) with sagittal imbalance.ADLS patients with sagittal imbalance underwent corrective surgery were included and divided into staged group (underwent multilevel LLIF in the first-stage and PIF in the second-stage) and control group . The clinical and radiological outcomes were evaluated and compared between the two groups.P<0.01), respectively. Posterior column osteotomy (PCO) was performed in 9 patients (36%) in the staged group, while PCO and/or pedicle subtraction osteotomy were performed in 15 patients (75%) in the control group (P<0.01). There was no difference in complications between the two groups.Forty-five patients with an average age of 69.7±6.3 years were enrolled, including 25 in the staged group and 20 in the control group. Compared with preoperative values, patients in both groups achieved significant improvement in terms of ODI, VAS back, VAS leg and spinopelvic parameters after surgery, which were maintained well during the follow-up period. Compared with control group, total operative time in the staged group was longer, but the amounts of blood loss and blood transfusion were reduced. The average posterior fixation segments were 6.20±1.78 in the staged group and 8.25±1.16 in the control group (Both surgical strategies were effective for the treatment of ADLS with sagittal imbalance. However, staged treatment was less invasive, which reduced the number of posterior fixation segments and osteotomy requirement. Adult degenerative lumbar scoliosis (ADLS) is a common spinal deformity in skeletally mature patients, characterized by a lateral curvature of spine in the coronal plane greater than 10°, asymmetric loss of disc height, lumbar kyphosis, and even global sagittal imbalance . The preSurgical treatment is recommended when the initial conservative treatment is unsatisfactory. However, surgical treatment for ADLS is challenging due to a high incidence of complications . DecomprIn recent years, there has been an increasing emphasis on minimally invasive treatment, with the aim of reducing surgical trauma and prompting rapid recovery. Transpsoas lateral lumbar interbody fusion (LLIF), as a minimally invasive surgical technique, allows the placement of large interbody cage on bilaterally lateral margins of the dense apophyseal ring, and subsequently results in indirectly neurological decompression and deformity correction –10. StagInstitutional review board approval was obtained. In this study, we retrospectively reviewed data of ADLS patients who underwent corrective surgeries in our institution between January 2016 and January 2019. The inclusion criteria included (1) older than 50 years; (2) the apical vertebrae in coronal plane is lower than L1 level; (3) coronal Cobb angle > 20°; (4) pelvic incidence (PI)/lumbar lordosis (LL) mismatchnt} 6 cm ; (6) conAccording to the different corrective strategies, the included patients were divided into staged group and control group. In the staged group, multilevel LLIFs were performed in the first-stage, and posterior pedicle screw fixation and fusion were performed in the second-stage. In the control group, the patients were managed by posterior pedicle screw fixation and fusion alone in single stage. The advantages and disadvantages of the two different surgical strategies were informed to the patients in detail before surgery, who made the final decision for the treatment. Informed consent was obtained from all patients.In the first-stage, lateral incision was usually made from the concave side of the scoliosis with patient positioned in lateral decubitus position after general anesthesia. Through retroperitoneal transpsoas trajectory, the lateral side of indicated disc space was exposed, and discectomy was performed until to the contralateral side. For anterior column realignment (ACR), high speed blur was used to remove the paravertebral bridging osteophyte, and anterior longitudinal ligament and annulus were completely released by using a long-handle scalpel or the surgeon’s method of choice. Polyetheretherketone interbody cages  with uniform 18 mm anteroposterior width were used. The lateral and vertical dimensions of the cages depended on the anatomic morphology of disc spaces. Allograft demineralized bone matrix combined with bone marrow aspirate were used as bone graft. The patients were encouraged to walk on the first day after the first-stage surgery.In the second-stage , the patients underwent posterior pedicle screw fixation and fusion. Laminectomy was performed at the levels with symptomatically neurological compression. Transforaminal lumbar interbody fusion (TLIF) was performed at L5/S1 level for patient with the following conditions:(1) nerve root compression or lumbar canal stenosis; (2) segmental instability or spondylolisthesis; (3) severe degeneration of L5/S1 disc; (4) previous surgical history; (5) more than 15° tilt of L5 vertebral body. Posterior column osteotomy (PCO) was performed in patients with PI/LL mismatch > 30° or thoracolumbar kyphotic deformity according to the radiographic examination after first-stage LLIF.Posterior pedicle screw fixation and fusion was performed in a standard fashion through posterior midline incision under prone position. Laminectomy was performed at the levels with symptomatically neural elements compression. TLIF was performed at unstable levels. PCO, pedicle subtraction osteotomy (PSO) or a combination was performed in patients with severe rigid sagittal and/or coronal deformities.By reviewing medical records, patients’ data regarding demographics, operative time, blood loss, blood transfusion, postoperative hospital stay, surgical details and complications were collected. For patients in the staged group, the blood loss and operative time was calculated by the sum of those during the first- and second-staged surgery. Postoperative short-term psoas weakness, thigh numbness, and pain were regarded as expected aspects of the recovery process, but were regarded as complications when these deficiencies persist beyond 6 months. Complications were categorized as major and minor according to the definition by Glassman et al. .Clinical and radiological assessments were performed preoperatively, postoperatively and at final follow-up. Back and leg pain was evaluated by Visual Analogue Scale (VAS) ranging from 0 (no pain) to 10 . Functional status was evaluated by Oswestry Disability Index (ODI).The following spinopelvic parameters were evaluated by using full-length anteroposterior and lateral radiographs: Cobb angle, coronal balance distance (CBD), SVA, LL, PI, pelvic tilt (PT) and PI/LL mismatch Fig. . Proximap-value<0.05.SPSS software  was used for statistical analysis. Continuous variables were expressed as meansP>0.05), respectively.A total of 45 patients were enrolled in this study with an average age of 69.71±6.29 years, including 25 in the staged group and 20 in the control group. The average follow-up duration was 26.07±6.64 months. The two groups were similar in terms of gender, age, body mass index (BMI), BMD, symptomatic duration, and follow-up duration . In the second-stage, TLIF at L5/S1 level was performed in 7 patients. The average lumbar interbody fusion levels were 3.60±0.82. The average posterior fixation segments were 6.20±1.78 in the staged group. PCO was performed in 9 patients (36%).P<0.01). The average posterior fixation segments were 8.25±1.16, which showed significant difference when compared to staged group (P < 0.01). Osteotomy was performed in 15 patients (75%), including PCO in 11 cases and PSO in 4 cases, respectively. There was significant difference between the two groups regarding the incidence of osteotomy (P < 0.01).For the control group, 58 levels of TLIF were performed for all the patients. The average lumbar interbody fusion levels were 2.90±0.79, which showed significant difference when compared to staged group , and the improvements were maintained till to the final follow-up visit (P < 0.01). No difference in clinical improvement was found between the two groups postoperatively and at the final follow-up.Regarding to the preoperative ODI, VAS back and VAS leg, no significant difference was found between the two groups Table . After sP < 0.01). Except Cobb angle (P = 0.04), no significant difference was found between the two groups regarding to postoperative CBD, SVA, LL, PT, and PI/LL mismatch. At the final follow-up, significant radiological improvements were maintained in both groups (P < 0.01), and no significant difference was found between the two groups.There were no significant differences between the two groups regarding to preoperative Cobb angle, CBD, SVA, LL, PT, PI and PI/LL mismatch Table . PostopeIn the staged group, 11 complications occurred in 8 patients (32%), including 7 minor and 4 major complications. Major complications were as follows: one case of deep wound infection treated with debridement; one case of deep vein embolism treated with inferior vena cava mesh placement; one case of pulmonary infection treated with antibiotics; one patient developed PJK 16 months after surgery and was treated conservatively.P = 0.37). Major complications were as follows: one case of deep wound infection treated with debridement; one case of deep vein embolism was treated with anticoagulant; one case of cerebral infarction was treated with medication and rehabilitation exercise; one case of permanent lower extremity radiculopathy; one patient developed PJK 20 months after surgery and underwent revision surgery. All patients with surgical-related complication in both groups achieved great prognosis after timely and effective treatment.In the control group, 11 complications occurred in 9 patients (45%), including 6 minor and 5 major complications , can only provide 5°-10° of segmental sagittal correction . Thus, PIn recent years, LLIF combined with PIF have been developed with good clinical results for the treatment of ADLS. Bae et al.  reportedThe purpose of staged treatment for severe ADLS is to reduce surgical invasiveness of each procedure. However, it may also prolong hospital stay and bed rest, leading to the development of related complications. Passias et al.  reportedThere are several limitations to the current study. Retrospective analysis reduced the evidence level. A small sample size was another weak point, limiting its statistical power. Further study is needed with a larger cohort included. Finally, the follow-up period is relatively short. A prolonged observation period is beneficial in the comparison of the efficacy of staged LLIF combined with PSF and PSF alone in the treatment of ADLS. Hence, a high-quality randomized controlled study of with larger sample size and longer follow-up duration is required to confirm our finding in the future.Both staged LLIF combined with PIF and PIF alone were effective treatments for ADLS with sagittal imbalance. However, staged treatment showed less surgical trauma, which reduced the number of posterior fixation segments and osteotomy requirement.


Walking and balance impairment are common sequelae of stroke and significantly impact functional independence, morbidity, and mortality. Adequate postural stability is needed for walking, which requires sufficient integration of sensory information between the visual, somatosensory, and vestibular centers. “Sensory reweighting” describes the normal physiologic response needed to maintain postural stability in the absence of sufficient visual or somatosensory information and is believed to play a critical role in preserving postural stability after stroke. However, the extent to which sensory reweighting successfully maintains postural stability in the chronic stages of stroke and its potential impact on walking function remains understudied.In this cross-sectional study, fifty-eight community-dwelling ambulatory chronic stroke survivors underwent baseline postural stability testing during quiet stance using the modified Clinical test of Sensory Interaction in Balance (mCTSIB) and assessment of spatiotemporal gait parameters.Seventy-six percent (45/58) of participants showed sufficient sensory reweighting with visual and somatosensory deprivation for maintaining postural stability, albeit with greater postural sway velocity indices than normative data. In contrast, survivors with insufficient reweighting demonstrated markedly slower overground walking speeds, greater spatiotemporal asymmetry, and limited acceleration potential.Adequate sensory system reweighting is essential for chronic stroke survivors’ postural stability and walking independence. Greater emphasis should be placed on rehabilitation strategies incorporating multisensory system integration testing and strengthening as part of walking rehabilitation protocols. Given its potential impact on outcomes, walking rehabilitation trials may benefit from incorporating formal postural stability testing in design and group stratification. Post-stroke walking impairment significantly reduces functional ambulatory independence and is a significant cause of worldwide morbidity and mortality , 2. CommPostural stability is the ability to maintain the center of gravity inside one’s base of support through discrete synergies of trunk and leg muscles and is activated both in quiet stance and during motion . EvidencN = 21)  . Yet, otN = 21) , 27–29. -completion) would demonstrate greater walking impairment .Hence, the objectives of this study were: (1) to characterize sensory reweighting in cohort of chronic stroke survivors (≥6 months post-stroke) and (2) to determine the relationship between postural stability and walking speed. We hypothesized that chronic stroke survivors would have greater postural instability across all four conditions of the modified Clinical test of Sensory Interaction in Balance (mCTSIB) compared to normative data. Second, participants with the most significant postural instability or the overt loss of balance  who had undergone baseline testing in two walking rehabilitation trials (NCT04553198 and NCT04721860) at the University of Cincinnati Neurorecovery Lab from August 2020 to February 2023 were included in this study. According to the Declaration of Helsinki recommendations, all participants provided written informed consent prior to enrollment. Inclusion criteria were: 18–80 years of age, residual walking impairment secondary to ischemic/hemorrhagic stroke(s) and ambulating at least 10 meters without a walker. All participants were able to walk independently without assistance of another person (with or without orthosis) or with an assistive device . In addition, all participants were expected to have abstained from formal physiotherapy and botulinum toxin injections at least 2 weeks before the screening visit . ExclusiThe mCTSIB is an established and reliable instrument for measuring static posture during quiet stance , 32, 33.While on the Biodex Balance Platform™ , with a safety harness and without body weight support or use of balance aids, participants were asked to stand with their hands at their sides, in comfortable double limb stance with shoes approximately shoulder width apart. The test was performed under the four different conditions of the mCTSIB, with each trial lasting 30 s, see The 10-meter walk test (10 MWT) is the gold standard measure of post-stroke walking function reflecting overall mobility and health status .A trained physical therapist used a handheld stopwatch to time participants over the 10-meter walkway to obtain the self-selected (SS) and fast-paced (FP) walking speeds. A two-meter space was provided prior to the starting and ending markers to allow for acceleration and deceleration, respectively. The timing started when the participant’s lead leg broke the plane of the starting marker and stopped when both legs crossed the marker at the end of the path. Participants were allowed to use their home assistive device and orthosis. First, participants were asked to walk at their SS speed. Next, they were asked to walk at their FP speed without running. There were two trials for each walking condition, and the respective results were averaged for analysis.SS walking speed is an universally accepted measure for classifying walking impairment level (household/severe vs. community ambulator/Mild–moderate) , while FDecreased paretic limb contribution to standing balance control has been associated with greater walking asymmetry and increased likelihood of falls due to the limited capacity of the paretic limb to respond to instability . SpecifiN = 2,195, Ages: 13–84) provided by Biodex was used for comparison , SVI (variable-independent), and non-completion (dichotomous-independent) were performed to determine the relationship between performance on each of the four test conditions and SS and FP walking speeds. The normative SVI value from the general population  compared to normative data (0.44 ± 0.48), p < 0.0001 , see Condition #2: Fifty-seven of fifty-eight (98%) participants completed the eyes-closed, fixed support surface condition testing somatosensory and vestibular systems’ contributions to postural balance in the absence of visual input. Chronic stroke survivors experienced greater SVI (1.64 ± 0.67) compared to normative data (0.80 ± 0.44), p < 0.0001 .Condition #3: Fifty-five of fifty-eight (95%) participants completed the eyes-opened foam surface condition, testing visual and vestibular systems’ contributions to postural stability when somatosensory information is perturbed. Chronic stroke survivors experienced greater SVI (1.42 ± 0.72) compared to normative data (0.79 ± 0.43), p < 0.0001 . Although three participants could not complete condition #3 (compared to only one for condition #2), the SVI was comparable between both conditions, p = 0.10 .Condition #4: Forty-five of fifty-eight (78%) participants completed the eyes-closed foam surface condition testing the contributions of the vestibular system alone and the relative dependence of vision and somatosensation on postural stability. Chronic stroke survivors experienced greater SVI (2.87 ± 0.83) compared to normative data (2.41 ± 0.38), p < 0.0001 .All 58 study participants completed the walking speed trials. Of these, 25 (43%) required the use of an assistive device during walking , including 15 who used an ankle foot orthosis (AFO). The average group SS walking speed was 0.62 ± 0.32 m/s and 0.89 ± 0.50 m/s for FP. The average group acceleration potential (FP-SS Speed) was 0.27 ± 0.21 m/s.Details demonstrating walking speed differences between Completers and Non-completers on mCTSIB, are in The average lower extremity temporal symmetry [single support time (s)] during SS and FP walking was 83.7% ± 10.4% and 84.6% ± 11.0%, respectively. The average lower extremity spatial symmetry [step length (cm)] was 89.0% ± 10.5% during SS and 89.0% ± 12.3% during FP walking. Details showing differences in spatiotemporal walking patterns between Completers and Non-completers on mCTSIB, are in n = 58), #2 (n = 57), #3 (n = 55), #4 (n = 45). There was a weak negative association between SVI in condition #1 and each walking speed: SS  and FP . Otherwise, there were no associations between SVI in conditions #2–4 and walking speed.The relationship between SVI and walking speed was assessed in participants who completed the posturography task: condition #1 , p = 0.15, R2 = 0.04]. However, there was a weak association between non-completion of condition #3 and walking speed , and a moderate association for non-completion of condition #4 . The average speed was faster for participants completing all four mCTSIB conditions [0.73 ± 0.27 m/s (SS) and 1.06 ± 0.43 (FP)] compared to participants unable to complete one or more conditions [0.23 ± 0.12 (SS) and 0.29 ± 0.17 (FP)], <0.0001, <0.0001 . Participants unable to complete one or more conditions of the mCTSIB were at or below the established threshold (<0.4 m/s) for self-selected walking speed necessary for community ambulation  , <0.00010., 0.66, <This study aimed to test postural stability during quiet stance and determine differences in visual and somatosensory reliance in our cohort of chronic stroke survivors. We also aimed to determine the relationship between postural stability and overground walking performance. Compared to normative data, we found significantly greater postural instability across all conditions in chronic stroke survivors. In addition, we found an increased reliance on visual and somatosensory systems in chronic stroke survivors, based on comparable SVI values in both conditions 2 and 3 of the mCTSIB, and higher SVI values in condition 4, when both are absent or perturbed, see In this observational study, all participants were able to complete condition #1 of the mCTSIB, suggesting that the cumulative input of the visual, somatosensory, and vestibular inputs was sufficient to prevent falls during quiet stance in the chronic stages of stroke recovery, irrespective of other factors associated with balance such as cognition, sensorimotor impairment, musculoskeletal strength, and coordination. In addition, there was a small negative association between the SVI and self-selected and fast walking speeds, suggesting that individuals with the greatest SVI under condition #1 are more likely to be slower walkers. We found no association between the SVI and walking speed in conditions #2–4. The absence of this relationship is likely due to the variability in sensory system integrity and implicit strategies used to maintain postural control across study participants. Another possible confounder is that participants with the greatest instability (non-completers) did not generate SVI values for inclusion into the correlation analysis, thereby decreasing the sample size and restricting the distribution of SVI values. Moreover, while postural stability during quiet standing and walking has many similarities, one possibility is that additional biomechanical variables not apparent during quiet stance, such as the shifting of the center of mass and motor activation time, become more relevant during walking , 42.Although there have been conflicting reports on sensory system reweighting in the chronic stages of stroke , 26, we Interestingly, 88% of our study cohort and 77% of non-completers had supratentorial strokes, as opposed to brainstem and cerebellar strokes—regions classically associated with postural control and balance. Recent reports have shed light on the importance of the human vestibular cortex in motor control, postural stability, and walking outcomes . SpecifiWhile task completers and non-completers were similar in characteristics such as age, chronicity of stroke, cognition, and stroke location, we found that the inability to complete one or more of the subcomponents of the mCTSIB was associated with slower walking speeds, greater spatiotemporal asymmetry, and diminished acceleration potential. This finding has both quality of life , 55 and Furthermore, this study found that non-completers were more likely to have had a hemorrhagic rather than an ischemic stroke. However, this finding warrants further investigation in a larger prospective study, as the impact that the stroke subtype (ischemic vs. hemorrhagic) on recovery and rehabilitation remains unsettled , 61. MorLastly, given possible associations between mCTISB completion and other clinical measures , one may infer that such measures can be used in lieu of the mCTISB. However, the mCTSIB provides valuable and objective information on sensorineural integration and reweighting not attainable with other measures. In addition, mCTSIB with posturography provides invaluable continuous data which can be tracked over the continuum of recovery and used to determine the effects of neurorehabilitative interventions on postural stability and walking outcomes.Since this study was observational and did not adjust for multiple comparisons, future prospective rehabilitation studies with age-matched controls are needed to validate our findings. Furthermore, while there was no reported or clinically evident vestibular dysfunction in our cohort, formal vestibulo-ocular reflex testing was not performed in this study, therefore the influence of subclinical vestibular dysfunction could not be entirely ruled out and limits the interpretation of our study findings beyond what is reported. Additionally, as designed, the study did not include non-ambulatory stroke survivors; therefore, our findings are not generalizable to that population. Moreover, while this study included many of the standard variables associated with post-stroke balance and walking, additional measures such as lower extremity motor impairment levels, lesion size, structural network integrity of critical pathways involved in sensorimotor integration, and the inclusion of ascending and descending electrophysiological measures may better predict the determiners of outcome. In addition, investigations into how center-of-pressure patterns unfold over time  may help to elucidate adaptability to changing contextual conditions and transfer between different functional tasks.Findings from this cross-sectional study in ambulatory chronic stroke survivors report insufficiencies in sensory systems processing at this stage of recovery and suggest that further consideration should be given to rehabilitation strategies incorporating multisensory system integration testing and strengthening as part of walking rehabilitation protocols. In addition, future walking rehabilitation trials should consider incorporating sensorineural processing measures to evaluate their prognostic potential.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The studies involving humans were approved by University of Cincinnati College of Medicine Institutional Board Review. The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation in this study was provided by the participants’ legal guardians/next of kin. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.OA, AG, CD, HS, PB, EW, ME, and KD: conception and design of the study, acquisition of data, or analysis and interpretation of data. OA, HS, SS, PB, AB, KD, PK, and BK: drafting the article or revising it critically for important intellectual content. All authors contributed to the article and approved the submitted version.