Poznan University of Medical Sciences

Introduction Intranasal adhesions (synechiae) are common complications of nasal surgery. This study aimed to analyze the factors influencing the development of synechiae, with particular emphasis on the use of nasal septal splints. We also propose a solution to reduce the incidence of this complication in the future. Methodology This retrospective analysis of patients ( n = 243) who underwent septoplasty and septoconchoplasty between 2017 and 2022. Results Iatrogenic intranasal synechiae occurred in 26.75% (65/243) of patients. Among patients who received nasal septal splints, synechiae occurred in 13.1%. Synechiae complicated 46.9% of the surgeries in the group without separators ( P < 0.001). There was no statistically significant relationship between increased risk of synechiae and concomitant conchoplasty (26% vs. 27.7%, P = 0.817). Patients with seton gauze dressings experienced synechiae significantly more often than those with nasal tampons or other gauze dressings ( P < 0.001). Conclusions The use of nasal septal separators and tampons significantly reduces the risk of iatrogenic intranasal synechiae following septoplasty or septoconchoplasty, regardless of the degree of nasal septum deviation. Conversely, the use of seton gauze dressings is associated with a higher risk of developing synechiae.

Purpose The aim of part one of this EU‐US consensus was to combine literature research and expertise to provide recommendations for the usage of rehabilitation (including physical therapy) of patients undergoing surgical treatment for degenerative meniscus lesions or acute meniscus tears (including meniscectomy, repair, or reconstruction). Prevention programmes, non‐operative treatment of acute tears and degenerative lesions, return to sports and patient‐reported outcome measures will be presented in a part II article. Methods This consensus followed the European Society for Sports Traumatology and Arthroscopy (ESSKA)'s ‘formal consensus’ methodology. For this combined ESSKA, American Orthopedic Society for Sports Medicine and American Academy of Sports Physical Therapy initiative, 67 experts (26 in the steering group and 41 in the rating group) from 14 countries (US and 13 European countries), including orthopaedic surgeons, sports medicine doctors and physiotherapists were involved. Steering group members established guiding questions, searched the literature and proposed statements. Rating group members assessed the statements according to a Likert scale and provided grades of recommendations, reaching a final agreement about rehabilitation of the knee after meniscus surgery. Final documents were then assessed by a peer review group to address the geographical adaptability. Results The overall level of evidence in the literature was low. Of the 19 questions (leading to 29 statements), 1 received a Grade A of recommendation, 2 a Grade B, 9 a Grade C and 17 a Grade D. Nevertheless, the mean median rating of all questions was 8.2/9 (9 being the highest rating on a scale of 1–9). The global mean rating was 8.4 ± 0.2, indicating a high agreement. Rehabilitation depends on the type of lesion, the treatment performed and is the same after medial or lateral meniscus surgery. Rehabilitation after meniscectomy should follow a criterion‐based rehabilitation protocol, based on milestones rather than a time‐based protocol. After meniscus repair and reconstruction, rehabilitation should be progressed according to both time and criterion‐based milestones. Conclusion Rehabilitation after meniscus surgery is a debated topic that may influence surgical outcomes if not optimally performed. This international formal consensus established clear, updated and structured recommendations for both surgeons and physiotherapists treating patients after meniscus surgery. Level of Evidence Level I, consensus.

Background Abscisic acid (ABA) regulates key plant processes, including seed germination, dormancy, and abiotic stress responses. While its physiological role in germination is well-documented, the molecular mechanisms are still poorly understood. To address this, we analyzed transcriptomic and metabolomic changes in ABA-treated germinating barley (Hordeum vulgare) embryos. To map ABA-responsive gene expression across embryonic tissues, we employed the Visium Spatial Transcriptomics (10× Genomics). This approach, which remains technically challenging to be applied in plant tissues, enabled the precise localization of gene expression across six embryo regions, offering insights into tissue-specific expression patterns that cannot be resolved by traditional RNA-seq. Results Transcriptomic analysis indicated that ABA acts primarily as a germination repressor. Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses linked ABA-inhibited genes to energy metabolism, lignin biosynthesis, cell wall organization, and photosynthesis, while induced genes were associated with environmental adaptation and phytohormone signaling. Differentially expressed genes (DEGs) correlated with metabolites involved in phytohormone pathways, including gibberellins, jasmonates, brassinosteroids, salicylic acid, auxins, and ABA metabolism. Comparisons with developing seed transcriptomes suggested an ABA-associated gene expression signature in embryos. Spatial transcriptomics technique made possible the precise identification of ABA-induced transcriptional changes within distinct embryonic tissues. Conclusions Integrating transcriptomics, metabolomics and spatial transcriptomics defined the molecular signature of ABA-induced modulation of phytohormonal crosstalk, energy metabolism, and tissue-specific gene activity in germinating seeds. The successful use of spatial transcriptomics adds a novel layer of resolution for understanding tissue-specific ABA responses during barley seed germination. These findings offer new insights into the ABA role in seed germination and potential strategies for enhancing crop resilience.

Purpose of Review The aim of our review is to summarize the available literature where metabolomics was used in studies on childhood asthma, and to find metabolites that are diagnostic biomarker candidates in childhood asthma. Moreover, the review also describes studies related to metabo-endotypes and heterogeneity of childhood asthma, severity of the disease, and response to drug treatment. Recent Findings Metabolomics has opened up new perspectives in childhood asthma investigation. Based on the available literature, we found nine metabolites that demonstrated the highest diagnostic potential for differentiation between children with asthma and healthy controls: adenine, adenosine, benzoic acid, hypoxanthine, p-cresol, taurocholate, threonine, tyrosine, and 1-methyl nicotinamide. Many of the identified metabolites are closely associated with inflammatory processes responsible for asthma. Metabolomic analysis also contributed to characterizing new asthma endotypes highlighting the heterogeneity of pediatric asthma. Summary Metabolomics can bring about valuable insights, which, when integrated with other omic disciplines, can facilitate the diagnosis and management of childhood asthma and the search for new biomarkers of the disease. Improvements in the detection of asthma in preschool children, including asthma endotypes, will ease application of proper treatment and enable elimination of unnecessary test treatment of corticosteroids in young patients.

Introduction Lateral extra-articular tenodesis (LET) is a surgical technique that can be used in conjunction with anterior cruciate ligament reconstruction (ACLR), improving rotational stability and reducing the risk of anterior cruciate ligament (ACL) re-rupture. However, as with any surgical procedure, LET carries a risk of complications. Despite numerous articles published in recent decades discussing LET in the context of ACLR, relatively few complications associated with the LET procedure have been documented in the literature. This study aimed to systematically review adverse events associted with the LET procedure when combined with ACLR. Material and methods The following key terms were used: (extra-articular OR extraarticular) AND (tenodesis OR plasty OR augmentation OR procedure or reconstruction OR reconstructive OR surgical OR surgery OR technique) AND (ACL OR anterior cruciate ligament), with no limits regarding the year of publication in PubMed, ScienceDirect, Cochrane Central, Web of Science, and Embase databases. English-language clinical human studies with evidence levels I-IV were included. Results This analysis evaluated seven articles published between 1999 and 2023. Level IV evidence was identified in the majority of studies (n = 5), level III evidence was found in one (n = 1), and level I evidence was noted in another (n = 1). Nine distinct types of complications were identified with rates rangingfrom 0.6% to 17% across the analysed studies. The modified Lemaire technique had the highest complication rate, reaching 7.5%. Overall, the complication rate across all reviewed LET techniques in this study was 4.2%. Conclusion This is the first study to systematically document the occurrence of complications in LET. The most common problems included LET hardware irritation – predominantly after staple fixation, and subsequent removal, haematoma over the LET site, and pain over the LET site. The analysed studies show that combining LET with ACLR appears to be a safe procedure associated with infrequent and mild side effects.

Background Xevinapant, an inhibitor of apoptosis protein (IAP) inhibitor, has shown promising activity in combination with anticancer agents, including radiotherapy, and, in preclinical studies, anti-PD-(L)1 antibodies. This, in part, is due to its ability to restore apoptosis and increase antitumour immunity. Objectives We report efficacy, safety and exploratory biomarker analyses of xevinapant plus avelumab (anti-PD-L1) in a two-part, open-label, nonrandomised, phase Ib study. Design Part A assessed patients with advanced solid tumours who received xevinapant (100, 150, 200 or 250 mg/day, with no random allocation, on Days 1–10 and 15–24) in combination with avelumab (10 mg/kg) on Days 1 and 15 in 28-day cycle. Part B assessed patients with advanced non-small-cell lung cancer (NSCLC) who received xevinapant at the recommended phase II dose (RP2D) plus avelumab (maximum 26 cycles). Methods Part A assessed the safety and tolerability of the combination and established the maximum tolerated dose (MTD) and RP2D of xevinapant. Part B assessed the antitumour activity of xevinapant at the RP2D combined with avelumab compared with a historical control (avelumab alone). Exploratory biomarker analyses were also conducted. Results In part A (n = 16), xevinapant 200 mg/day was established as the RP2D with avelumab and the MTD was not reached. The most common treatment-emergent adverse events (TEAEs) irrespective of xevinapant dose were nausea and fatigue (n = 11 (68.8%) each). In part B (n = 38; four patients received prior anti-PD-(L)1 antibody), the objective response rate (ORR) was 10.5% (95% confidence interval (CI), 2.9–24.8; partial response, n = 4) and the most common TEAE was decreased appetite (n = 13 (34.2%)). Levels of plasma IL-10, IL-1β, IL-13 and CD8⁺ T cells increased during the study, and circulating levels of CD4⁺ T cells and Tregs increased during cycle 1. Macrophage-related gene expression signatures increased in patients with a partial response or stable disease. Low baseline Ki-67 expression in tumour samples correlated with a partial response. Conclusion The RP2D of xevinapant with avelumab was established; however, the ORR was not superior to the historical control (avelumab alone). The combination had a manageable safety profile in both study parts. Biomarker analyses provide insights into drivers associated with efficacy in patients with NSCLC receiving xevinapant plus avelumab. Trial registration NCT03270176 (https://clinicaltrials.gov/study/NCT03270176). Registered on ClinicalTrials.gov on 29 August 2017.

We analysed cognitive impairment (CI) during the peri-myocardial infarction (MI) period and after 6 months. The study included 326 patients. Cognitive function was assessed using the Mini–Mental State Examination (MMSE) and the Clock Drawing Test (CDT). Routine laboratory and echocardiography data were collected. We distinguished 4 groups of patients: 1 – CI present peri-infarction and after 6 months; 2 – CI present only peri-infarction; 3 – CI present only after 6 months; 4 – without CI. Groups constituted 8.9%, 16.3%, 7.7% and 67.1% of participants (as assessed by MMSE), respectively. In those who improved (group 2) or with worsened cognitive function (group 3), analogous changes in attention function occurred. There was a group of patients with CI on the MMSE who performed the CDT correctly, 12% peri-infarct and 11% at 6-month follow-up, respectively. Patients with a normal CDT score but CI found in the MMSE had impaired attention function. Cognitive function improves in some patients, and deteriorates in others after MI. The uniform type of impaired cognitive function allows us to assume a uniform etiology of CI. Performing the CDT and using the MMSE component assessing attention could prove sufficient for the initial assessment of cognitive functions in patients after MI.

Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrine disorders affecting women of reproductive age, with an estimated prevalence of 5–10%. Women with PCOS are at increased risk for metabolic disturbances. A significant proportion of women with PCOS, ranging from 40 to 85%, are either overweight or obese. Oral contraception is the standard first line treatment for PCOS. However, certain conditions associated with PCOS, such as obesity, must be considered when deciding to prescribe combined oral contraception. It seems that there is no clinical advantage in using high-dose ethinyl estradiol over low-dose formulations. Lower-dose EE formulations may be considered a safer option for obese PCOS patients. Combined oral contraception containing natural estrogens, which have a beneficial effect on metabolic parameters, could also be a viable option for this group. Progestin-only (POPs) formulations have minimal metabolic effects, making them a safe contraceptive choice for patients with obesity and a high risk of coronary artery disease, cerebrovascular disease, venous thromboembolism, or hypertension. Non-oral contraceptive methods, such as transdermal patches and vaginal rings, offer a valuable alternative for women with PCOS who prefer not to use daily oral contraceptives. However, the absence of anti-androgenic progestins in these contraceptive methods may limit their effectiveness, especially for women with moderate to severe clinical signs of androgen excess. The use of LNG-IUDs in women with PCOS may be beneficial in several ways. First, in cases where other contraceptive methods are contraindicated, the LNG-IUD provides effective contraception while also regulating abnormal uterine bleeding. Additionally, the relative hyperestrogenism associated with anovulation in PCOS can lead to endometrial hyperplasia with atypia and, in severe cases, endometrial cancer. Therefore, in women with both PCOS and obesity, the LNG-IUD may be preferred over oral megestrol acetate for endometrial protection.

Introduction Recombinant human growth hormone (rhGH) therapy (GHT) for short stature resulting from growth hormone deficiency (GHD) is effective in promoting optimal growth velocity and achieving an appropriate final height. However, the specific metabolic changes in children during replacement GHT remain unclear. Content The study aimed to evaluate the effects of GHT on metabolism in children with GHD. This is a review of the literature published at PubMed/MEDLINE between January 2010 and August 2024, including original articles. The authors searched Medline using the following keywords: growth hormone therapy in children OR growth hormone treatment in children AND metabolism OR glycemia OR glycated hemoglobin OR insulin OR lipid profile OR blood pressure OR bone mineral density OR body mass index OR waist circumference OR hip circumference OR waist-to-hip ratio OR lean body mass OR visceral fat OR muscle strength OR physical activity OR exercise. Summary and Outlook GHT in children positively affects the lipid profile and body composition. Nevertheless, rhGH treatment may increase fasting glucose, glycated hemoglobin, and indices of insulin resistance. GHT in children has not been associated with an increased risk of diabetes. No changes in blood pressure during GHT were observed. The results of our review show that GHT impacts lipid profiles, carbohydrate metabolism, and body composition. Further studies are needed to clarify the molecular mechanisms by which GH regulates substrate metabolism. Keywords: growth hormone deficiency; short stature; final height; glycemia; lipid profile; body composition

Coronary artery disease (CAD) is common in patients burdened with metabolic syndrome. Increased risk of cardiovascular disease is associated with abnormal levels of acylated derivates of carnitine. The present study aimed to evaluate the possible association between carnitine derivatives and coronary artery disease, including obese individuals. Twenty consecutive patients presenting with dyspnea on exertion were enrolled in the prospective analysis for metabolomic profiling. They were divided into two groups regarding CAD presence. Six (60%) men and four (40%) women comprised the CAD group assigned as Group 1, while 6 (60%) men and 4 (40%) women with normal coronary arteries on angiograms as Group 2. Compared to the non-CAD group, the CAD group was characterized by lower levels of the sum of long-chain ACs (p = 0.024), the sum of short-chain ACs (p = 0.022), saturated fatty acids (SFA) (p = 0.030) and monounsaturated fatty acids (MUFA) (p = 0.022). Further subanalysis concerning patients’ body mass index and CAD showed significant differences in plasma sum of ACs between the groups (p = 0.050) and SFA (p = 0.050) but not regarding the short-chain ACs (p = 0.060), medium-ACs (p = 0.758), long-chain-ACs (p = 0.141), or MUFA (p = 0.151). Our analysis revealed lower plasma levels of short-chain and saturated fatty acids acylcarnitine derivates in obese patients presenting with CAD.

This chapter highlights procedures that are specific to the assessment of a patient with a uveal tumor. These include slit-lamp examination, gonioscopy, binocular indirect ophthalmoscopy, transillumination, and color photography. Preparation of drawings complements imaging and may be useful for documenting disease and planning treatment. Other investigations, such as autofluorescence imaging, optical coherence tomography, and ultrasonography are described in other chapters. It is assumed that a full ophthalmic and systemic history is routinely obtained in all patients in addition to clinically relevant ancillary investigations.

Monoallelic variants in the nuclear factor kappa B 1 (NFKB1) gene reinforce the functional haploinsufficiency causing immunodeficiency with marked individual and intrafamilial variability in genotype-phenotype correlations. The leading clinical manifestations of NF-κB1 deficiency are recurrent infections and immune dysregulation disorders with autoinflammatory and lymphoproliferative disease. The reported patient initially presented with a neonatal sepsis-like illness with meningitis because of a parechovirus infection. The diagnosis of an inborn error of immunity, common variable immunodeficiency (CVID), was established based on hypogammaglobulinemia, impaired antibody response to vaccines, IgG subclass deficiency, and low numbers of switched memory B cells. Molecular genetic testing using trio whole exome sequencing was done to define the background of the presenting phenotype, and it revealed a novel heterozygous variant of NFKB1. Viral meningitis and sepsis-like illness are unusual, previously unreported, infectious complications in NF-κB1 deficiency. The transcriptional NF-κB1 regulatory effect on different target gene repertoires and numerous processes including immune and inflammatory responses may indiacte the vulnerability of deficient patients to severe viral infections. This case report exemplifies the advancement of immuno-genetics paving the way for the transition from the initial era of clinical recognition to the era of molecular diagnosis of the pediatric CVID.

The study was conducted prospectively on 107 children (74 boys). Eighty-three children were born at term (39 ± 1), 24 were born prematurely (33 ± 4). The study included the qualitative assessment at three months of age, eye contact and traction response assessment, and the quantitative assessment at 3, 9, and 16 months of age. The timely achievement of crawling and sitting down depended on the same qualitative characteristics at three months of age: hands and lower limbs and on the segmentally extended spine and shoulder blades. Social walking was influenced by the qualitative assessment of the position of the lower limbs at three months of age. The eye contact substantially impacted walking; the correct traction test moderately impacted crawling and sitting down. The qualitative assessment at three months is highly predictive for crawling and sitting down at nine months and social walking at 16 months. The correct traction test appears to predict crawling and sitting down, while eye contact is essential for social walking.

Dominantly inherited GAA repeat expansions in the FGF14 gene have recently been identified as the cause of spinocerebellar ataxia 27B (SCA27B). Our study focused on a Polish patient case along with asymptomatic family members. Moreover, we systematically reviewed available case reports to better understand the SCA27B phenotype. Genetic tests for SCA27B were performed on genomic DNA isolated from blood. Long-range polymerase chain reaction (LR-PCR) followed by Nanopore sequencing was conducted to establish the number of GAA repeats. The available literature was systematically reviewed per the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-analyses. The patient’s genetic studies identified pure expansions of (GAA) 420/94 repeats in FGF14, confirming the SCA27B diagnosis. A systematic review of 815 cases provides further insight into the typical clinical presentation, with gait ataxia (95.96%) being the most prevalent symptom, followed by abnormal saccadic pursuits (80.69%), nystagmus (71.15%), diplopia (54.05%), and dysarthria (51.22%). Notably, 41.87% of cases exhibited episodic symptoms. The correlation between GAA repeat expansions and the pathogenesis of SCA27B requires further studies. The unique course of the disease with episodic symptoms may cause diagnostic difficulties. Due to its high prevalence in the European population, SCA27B should be considered when diagnosing the causes of late-onset cerebellar ataxia.

Continuous positive airway pressure (CPAP) is a standard treatment for children with moderate to severe respiratory distress; however, ventilators are often unavailable in developing countries. Bubble CPAP (bCPAP) is considered a simple, cost effective and less invasive alternative to CPAP, however, its efficacy has not been assessed for children with pneumonia until recently. This meta-analysis aims to compare the effectiveness of bCPAP with low-flow oxygen for treating severe pneumonia and hypoxemia in children. PubMed, EMBASE, Cochrane Library, Web of Science, and CENTRAL were searched to identify eligible randomized controlled trials reported up to March 23, 2024. Outcomes were reported as risk ratios (RRs) or mean difference (MD) and confidence intervals (CIs) using Review Manager software. P value < 0.05 was considered statistically significant. Three studies with 2030 patients were included and revealed no significant difference between bCPAP and control in overall mortality [RR (95% CI) 0.46 (0.09, 2.32); P = 0.348], death during hospital stay [0.48 (0.02, 9.09), P = 0.619], composite primary outcome [0.48 (0.12, 1.97), P = 0.301], pneumothorax [1.94 (0.16, 23.11), P = 0.601], leaving hospital against medical advice [0.63 (0.16, 2.39), P = 0.489], and length of hospital stay [MD (95%CI) 0.15 days (− 0.66, 0.96), P = 0.706]. Children on bCPAP had significantly fewer events of severe hypoxemia [RR (95% CI) 0.22 (0.10, 0.49), P < 0.001], and less requirement for mechanical ventilation [RR (95% CI) 0.38 (0.15, 0.99), P = 0.048]. bCPAP is not superior to low-flow oxygen for improving survival and reducing hospital stay in children with pneumonia, albeit the need for mechanical ventilation decreases.

Alveolar echinococcosis is parasitic disease caused by Echinococcus multilocularis and spread endemically in the northern hemisphere. Although alveolar echinococcosis is considered a rare disease, with approximately 18,000 new cases diagnosed annually, it continues to present significant diagnostic and therapeutic challenges. Alveolar echinococcosis affects the liver through slow, asymptomatic infiltration over many years. At the time of diagnosis, approximately 70% of cases are not eligible for radical lesion resection. The aim of the study was to evaluate whether non-radical surgery increases patients’ survival rates. We conducted a prospective analysis on patients diagnosed with alveolar echinococcosis in years 1995–2017 who underwent liver resection. Age, gender, mass of lesion, extensive nature of the operation (radical vs. conservative) and surgical procedures were collected. Mortality was analyzed. Mean resected lesions’ weight was statistically higher in non-radically resected group 1396,00 g (SD ± 845,39) compared with radically resected group 549,43 g (SD ± 364,27), p = 0,004. The type of surgical treatment did not significantly affect patient survival. The complete lesion resection (in combination with albendazole) is only a curative therapy, if feasible. In advance stages when radical resection is not feasible, the reductive or debulking surgery should be done for symptoms’ alleviation and quality of life improvement.

Aim To determine how different cord clamping strategies affect cerebral oxygenation in the first 15 min after birth in preterm infants. Methods A post-hoc secondary outcome analysis of a multicentre prospective randomised clinical trial (COSGOD III) conducted between October 2017 and October 2021 in 11 tertiary neonatal intensive care units in six countries in Europe and in Canada. In the present ancillary study, all included premature neonates (<32 weeks gestation) were retrospectively assigned to three groups according to the timing of cord clamping (G1<30 s, G2 30–60 s, G3>30 s). The aim of this study was to evaluate differences in cerebral regional oxygen saturation (crSO2) and cerebral fractional tissue oxygen extraction (cFTOE) within the first 15 min after birth in preterm neonates based on the timing of cord clamping. Results 572 infants (n=339 (G1), n=164 (G2) and n=69 (G3)) were included in the final ancillary analysis. There were no statistically significant differences in crSO2 and cFTOE between the three groups. There were no statistically significant differences between the three groups in neonatal morbidities, particularly importantly in the degree of cerebral injury, as measured by any degree of intraventricular haemorrhage or cystic periventricular leukomalacia. Conclusions No significant differences in crSO2 and cFTOE during the first 15 min after birth were observed; however, some effect may have been modified by protocol-guided titration of supplemental oxygen in the intervention arm. Thus, in our study, we did not find a correlation between deferred cord clamping and improved cerebral oxygenation immediately after birth. Trial registration number NCT03166722.