Prospective Case-control Study Research Articles

Multicentre case–control study of pneumococcal infections among children with pneumonia in Peninsular Malaysia (MY-Pneumo): a study protocol

BackgroundS. pneumoniae (SPN) is the most common cause of pneumonia. The disease can be effectively prevented through immunisation. Since December 2020, the Malaysian Government has included the 10-valent pneumococcal conjugate vaccine (PCV10) for all infants born on or after 1 January 2020 as part of the National Immunisation Programme (NIP). However, the epidemiology of pneumonia remains poorly understood. To fill the knowledge gap, we established a multicentre surveillance study to understand the burden of pneumococcal pneumonia among young children in Peninsular Malaysia.MethodsMY-Pneumo is a multicentre prospective case–control study conducted in three sentinel sites located in three different states of Peninsular Malaysia – Kuala Lumpur, Pahang, and Kelantan. A cohort of at least 500 incident cases and 500 controls is enrolled beginning in October 2021 and matched for age. Cases are hospitalised children < 5 years with radiologically confirmed pneumonia, and the controls are children without any features suggestive of pneumonia. Clinical samples, including nasopharyngeal swabs (NPS) and urine, are collected according to the study protocol. Biological fluids such as blood, cerebrospinal fluid (CSF) and pleural fluid are obtained from invasive pneumonia disease (IPD) patients, if available. All children are tested for SPN using polymerase chain reaction (PCR) and pneumococcal urine antigen test (PUAT) using BinaxNow.DiscussionSurveillance data, including carriage rate, serotype variations and the phylogeny data structure of SPN among young children in Malaysia during PCV implementation, will be generated from this study. Trends and patterns of pneumococcal serotypes by different regions are important for targeted public health strategies. Our data will provide baseline information for estimating the impact of PCV10 implementation and will influence policymakers' decisions regarding the upgrade from PCV10 to a higher-valency conjugate vaccine in Malaysia.Trial registrationThis project was registered at ClinicalTrials.gov (NCT04923035) on 2021, June 11. The study protocol was approved by the International Medical University Joint-Committee on Research & Ethics (4.15/JCM-216/2021) and the Institutional Review Board at sentinel sites (USM/JEPeM/21020190, IREC 2021–114, MREC ID No: 2021128–9769) and University of Southampton's Ethics and Research Governance (ERGo II 64844).

The Relationship between Circulating Kidney Injury Molecule-1 and Cardiovascular Morbidity and Mortality in Hemodialysis Patients.

The importance of identifying mortality biomarkers in chronic kidney disease (CKD), and especially in patients treated with hemodialysis (HD), has become evident. In addition to being a marker of tubulointerstitial injury, plasma kidney injury molecule-1 (KIM-1) has been mentioned in regard to HD patients as a risk marker for cardiovascular (CV) mortality and coronary artery calcification. The aim of this study was to assess the level of plasma KIM-1 as a marker of cardiovascular disease (CVD) and mortality in CKD5-HD patients (patients with CKD stage G5D treated with hemodialysis). We conducted a prospective case-control study that included 63 CKD5-HD patients (HD for 1-5 years) followed up for 48 months and a control group consisting of 52 non-dialysis patients diagnosed with CKD stages G1-G5 (ND-CKD). All patients had a CVD baseline assessment including medical history, echocardiography, and electrocardiography (ECG). Circulating plasma KIM-1 levels were determined with single-molecule counting immunoassay technology using an enzyme-linked immunosorbent assay. We obtained the following parameters: serum creatinine and urea; the inflammation markers CRP (C-reactive protein) and IL-6 (interleukin-6); and the anemia markers complete blood count, serum ferritin, and transferrin saturation (TSAT). The mean plasma KIM-1 level was 403.8 ± 546.8 pg/mL, showing a statistically significant correlation with inflammation (CRP, R = 0.28, p = 0.02; IL-6, R = 0.36, p = 0.005) and with anemia (hematocrit, R = -0.5, p = -0.0316; hemoglobin (Hb), R = -0.5, p = 0.02). We found that patients with left ventricular hypertrophy (LVH) on echocardiography (59.7%) had significantly lower mean levels of plasma KIM-1 than patients from the control group (155.51 vs. 432.12 pg/mL; p = 0.026). Regarding the patients' follow-up, we assessed all-cause mortality as an endpoint. After 24 months of follow-up, we found a mortality rate of 22.23%, while after 48 months, the mortality rate was 50.73%. A plasma KIM-1 level < 82.98 pg/mL was significantly associated with decreased survival in hemodialysis patients (p < 0.001). In patients treated with hemodialysis, low levels of plasma KIM-1 were associated with cardiovascular changes and an increased risk of mortality. Plasma KIM-1 levels were significantly higher in HD patients compared to ND-CKD patients.

Transorbital B-mode ultrasound for the assessment of posterior globe flattening in idiopathic intracranial hypertension: a pilot study

BackgroundPosterior globe flattening (PGF) is a specific neuroimaging sign in patients with idiopathic intracranial hypertension (IIH), but its detection is based on subjective qualitative neuroradiological assessment. This study sought to evaluate the utility of transorbital ultrasound to detect and quantify PGF in IIH patients using the Posterior Globe Angle (PGA).MethodsConsecutive IIH patients and healthy controls were enrolled in a prospective case-control study. Transorbital ultrasound was performed to assess the presence of PGF. For quantification of PGF, an angular measurement (PGA) was performed with the vertex centering the optic nerve at a predefined distance from the lamina cribrosa and angle legs tangentially aligned to the borders of the vitreous body. PGA measurements were compared between IIH patients and healthy controls. Additionally, the diagnostic accuracy of PGA measurements in detecting PGF was evaluated using ROC analysis.ResultsThirty-one IIH patients (37.3 ± 12.3 years, 29 female) and 28 controls (33.3 ± 11.8 years, 21 female) were compared. PGF was present in 39% of IIH patients and absent in the control group. PGA3mm measurements significantly differed between IIH and controls (116.5° ± 5.5 vs. 111.7° ± 2.9; p < 0.001). A PGA3mm cutoff of ≥ 118.5° distinguished IIH patients from controls with 100% specificity, while retaining a sensitivity of 37.5%.ConclusionsTransorbital ultrasound may be applied to detect and quantify PGF in IIH patients. Prospective, multicenter studies with extended cohorts and blinded design are needed to validate these preliminary findings and confirm the diagnostic utility of transorbital ultrasound for the assessment of PGF in IIH.

The Impact of Non-Dysentery Shigella Infection on the Growth and Health of Children over Time (INSIGHT)-A Prospective Case-Control Study Protocol.

(1) Shigella spp. (Shigella) is known for causing dysentery with blood in stool, but most children infected with Shigella have non-dysentery Shigella-associated diarrhea (NDSD). The World Health Organization recommends the use of antibiotics when diarrhea is bloody, leaving most NDSD cases untreated. The absence of dysentery may not indicate a low risk of death and severe morbidity. Rapid diagnosis and treatment of shigellosis in vulnerable, young children may be lifesaving. INSIGHT aims to determine the potential benefit of identifying NDSD cases (n = 296) and their outcomes compared to cases of Shigella dysentery [DS (n = 148)] and non-Shigella watery diarrhea [WD (n = 148)]. (2) Children seeking care at hospitals in Bangladesh will be enrolled and followed for 1 year (NDSD and DS) or 90 days (WD). We will determine the impact of NDSD on morbidity, mortality, gut health, nutritional status, and cognitive development compared to DS and WD in children and whether the simple "Rapid LAMP-based Diagnostic Test (RLDT)" can accelerate the detection and treatment of shigellosis in the clinical settings of rural Bangladesh. (3) INSIGHT will determine the impact of NDSD in children and determine if the treatment guidelines of shigellosis need to be revisited to improve clinical outcomes and the development of these children.

Enhancing Comprehensive Assessments in Chronic Heart Failure Caused by Ischemic Heart Disease: The Diagnostic Utility of Holter ECG Parameters.

Background and Objectives: Chronic heart failure (CHF) caused by ischemic heart disease (IHD) is the leading cause of death worldwide and presents significant health challenges. Effective management of IHD requires prevention, early detection, and treatment to improve patient outcomes. This study aims to expand the diagnostic utility of various 24 h Holter ECG parameters, such as T-wave alternans (TWA), late ventricular potentials (LVPs), and heart rate variability (HRV) in patients with CHF caused by IHD. Additionally, we seek to explore the association between these parameters and other comorbid conditions affecting the prognosis of CHF patients. Materials and Methods: We conducted a prospective case-control study with 150 patients divided into two subgroups: 100 patients with CHF caused by IHD, and 50 patients in the control group. Data included medical history, physical examination, laboratory tests, echocardiography, and 24 h Holter monitoring. Results: Our comparative analysis demonstrated that both TWA and LVPs were significantly higher in patients with CHF compared to the control group (p < 0.01), indicating increased myocardial electrical vulnerability in CHF patients. Both time and frequency-domain HRV parameters were significantly lower in the CHF group. However, the ratio of NN50 to the total count of NN intervals (PNN50) showed a borderline significance (p = 0.06). While the low-frequency (LF) domain was significantly lower in CHF patients, the high-frequency (HF) domain did not differ significantly between groups. Acceleration and deceleration capacities were also significantly altered in CHF patients. Categorizing CHF patients by left ventricular ejection fraction (LVEF) revealed that the mean of the 5-min normal-to-normal intervals over the complete recording (SDNN Index) was significantly higher in patients with LVEF ≥ 50% compared to those with CHF with reduced EF and CHF with mildly reduced EF (p < 0.001), whereas the other HRV parameters showed no significant differences among the groups. Conclusions: Holter ECG parameters can become a reliable tool in the assessment of patients with CHF. The integration of multiple Holter ECG parameters, such as TWA, LVPs, and HRV, can significantly enhance the diagnostic assessment of CHF caused by IHD. This comprehensive approach allows for a more nuanced understanding of the patient's condition and potential outcomes.

Differences in pulmonary function measured by oscillometry between horses with mild-moderate equine asthma and healthy controls.

The diagnosis of mild-moderate equine asthma (MEA) can be confirmed by airway endoscopy, bronchoalveolar lavage fluid (BALf) cytology, and lung function evaluation by indirect pleural pressure measurement. Oscillometry is a promising pulmonary function test method, but its ability to detect subclinical airway obstruction has been questioned. To evaluate the differences in lung function measured by oscillometry between healthy and MEA-affected horses. Prospective case-control clinical study. Thirty-seven horses were divided into healthy and MEA groups, based on history and clinical score; the diagnosis of MEA was confirmed by airway endoscopy and BALf cytology. Horses underwent oscillometry at frequencies ranging from 2 to 6 Hz. Obtained parameters included whole-breath, inspiratory, expiratory, and the difference between inspiratory and expiratory resistance (Rrs) and reactance (Xrs). Differences between oscillometry parameters at different frequencies were evaluated within and between groups by repeated-measures two-way ANOVA and post hoc tests with Bonferroni correction. Frequency dependence was compared between groups by t test. For significant parameters, a receiver operating characteristics curve was designed, cut-off values were identified and their sensitivity and specificity were calculated. Statistical significance was set at p < 0.05. No significant differences in Xrs and Rrs were observed between groups. The frequency dependence of whole-breath and inspiratory Xrs significantly differed between healthy (respectively, -0.03 ± 0.02 and -0.05 ± 0.02 cmH2O/L/s) and MEA (-0.1 ± 0.03 and -0.2 ± 0.02 cmH2O/L/s) groups (p < 0.05 and p < 0.01). For inspiratory Xrs frequency dependence, a cut-off value of -0.06 cmH2O/L/s was identified, with 86.4% (95% CI: 66.7%-95.3%) sensitivity and 66.7% (95% CI: 41.7%-84.8%) specificity. Sample size, no BALf cytology in some healthy horses. Oscillometry can represent a useful non-invasive tool for the diagnosis of MEA. Specifically, the evaluation of the frequency dependence of Xrs may be of special interest.

Frequency of seropositive celiac disease and hypothyroidism among children and adolescents with congenital heart disease: A case-control study

BackgroundThe prevalence of celiac disease (CD) and hypothyroidism exhibit significant variation in different studies among patients with congenital heart disease (CHD). This study evaluated the frequency of laboratory test abnormalities in children and adolescents with CHD in Shiraz, Iran.MethodsThis prospective case-control study was conducted on 223 children and adolescents with CHD and healthy individuals referred to the heart clinic affiliated with Shiraz University of Medical Sciences between February 2019 and December 2021. They were classified into case and control groups. Blood tests were performed for total IgA antibody, anti-tissue transglutaminase IgA antibody (anti-TTG Ab), T4, and thyroid stimulating hormone (TSH) and anti-thyroid peroxidase antibodies in serum, along with transthoracic echocardiography. Likewise, demographic characteristics of patients, including age, sex, weight, height, and body mass index (BMI), were recorded. Also, anti-TTG Ab levels were compared among CHD patients according to cyanosis status, gender, age (above and below five years), and BMI (under and over 18.5).ResultsNinety-eight CHD patients and 100 healthy individuals with an average age of 5.32 ± 4.05 years (1–18 years) were examined. In children with CHD, atrial septal defect (27%), ventricular septal defect (20%), and tetralogy of Fallot (13%) were the most prevalent disorders. Only one CHD patient had an anti-TTG Ab level of 16.6 unit/mL, considered borderline for seropositive CD diagnosis. There was no difference in anti-TTG Ab levels between age (above and below five years), BMI (under and over 18.5), cyanosis status, and gender groups. Seven CHD patients had high TSH levels, three had cyanotic CHD, and one had Down syndrome. The TSH levels and non-autoimmune hypothyroidism were significantly higher in CHD patients than in normal subjects (p < 0.05).ConclusionsAccording to the results of this study, the serum level of TSH and prevalence of non-autoimmune hypothyroidism were higher in patients with CHD than in normal subjects, but the serum level of anti-TTG Ab was not different between the two groups.

Assessing Full Stomach Prevalence with Ultrasound Following Preoperative Fasting in Diabetic Patients with Dysautonomia: A Comparative Observational Study.

Traditionally, diabetics have been considered patients with a high risk of aspiration due to having delayed gastric emptying; However, the evidence concerning residual gastric volume (GV) in fasting diabetic patients is inconsistent. This study aimed to compare the fasting GV of diabetic patients with or without dysautonomia with control patients scheduled for elective surgery using gastric ultrasound. This bicentric prospective single-blinded case-control study was conducted at 2 university hospitals in Spain. Patients aged over 18 years, classified as American Society of Anesthesiologists (ASA) physical statuses I to III and having similar fasting statuses, were included in the study. The primary outcome was to compare the prevalence of risk stomach using the Perlas gastric content grading scale evaluated by ultrasound in the 3 groups. Secondary outcomes included the measurement of cross-sectional area (CSA) and GV in the right lateral decubitus (RLD) position, as well as the prevalence of solid gastric residue. A total of 289 patients were recruited for the study, comprising 145 diabetic patients (83 of whom had dysautonomia) and 144 patients in the control group. The percentage of patients classified as Perlas grade 2 was 13.2% in the control group, 16.1% in diabetic patients without dysautonomia, and 22.9% in diabetic patients with dysautonomia (P = .31). Antral CSA was significantly higher in diabetic patients with dysautonomia (6.5 [4.8-8.4]) compared to the control group (5.4 [4.0-7.2]; P = .04). However, no significant differences were observed between groups in residual GV. Among diabetic patients with dysautonomia, 12% exhibited solid gastric residue, which was twice the percentage observed in diabetic patients without dysautonomia (4.8%) and 3 times higher than that in the control group (3.5%; P = .03). The presence of dysautonomia was associated with an increased odds ratio of solid gastric residue (odds ratio [OR], 3.37; 95% confidence interval [CI], 1.28-8.87; P = .01) after adjusting for confounding factors. This study offers insights into the relationship between dysautonomia in patients with diabetes mellitus and the presence of full stomach, underscoring the significance of preoperative gastric ultrasound evaluation in managing perioperative risks in this population.

Evaluation of Choroidal Thickness and Retinal Vessel Density with Serum HIF-1α and TNF-α Level in Patients with OSAS

Purpose To reveal changes in choroidal thickness, retinal vessel density, and serum HIF-1α and TNF-α levels in obstructive sleep apnea syndrome (OSAS) and their correlation. Methods This prospective case-control study included 118 patients divided into mild-to-moderate OSAS (n = 40), severe OSAS (n = 39), and a control group (n = 39). Choroidal thickness was evaluated with OCT, vessel density with OCTA, AHI index with polysomnography, and serum HIF-1α and TNF-α levels were analyzed using the enzyme-linked immunosorbent assay. Results The serum HIF-1α values of the participants in the mild-moderate OSAS and severe OSAS groups were [893.25(406.7–2068) and 1027(453–2527), respectively], and were both significantly higher than the control group [(521.5(231.6–2741))] (p < 0.001). Serum TNF-α levels did not differ significantly between the groups (p = 0.051).). Subfoveal choroidal thickness (SFCT) values of the severe OSAS groups were significantly lower than the control group (p < 0.05). The superficial and deep capillary plexus vascular density (SVD and DVD) values of the severe OSAS group were lower than the control group (p < 0.05). Serum HIF-1α and TNF-α levels of all participants were negatively correlated with both their SVD values (p < 0.05, r: –0.220 and p < 0.05, r: –0.252, respectively) and their DVD values (p < 0.001, r: –0.324 and p = 0.001, r: –0.299, respectively). Conclusions Increased serum levels of inflammatory mediators (HIF-1α ve TNF-α) in OSAS cause a decrease in SFCT, SVD, and DVD, which is an indication of systemic vascular damage. Further research on developing treatment strategies to modulate TNF-α ve HIF-1α may help recede vascular morbidity in OSAS patients.

Usefulness of combined pseudo-continuous arterial spin labelling and spectroscopic analysis in schizophrenic Egyptian population sample

BackgroundSchizophrenia is a prevalent psychiatric disorder that affects 1% of the global population. Schizophrenia frequently begins in late adolescence or early adulthood, causing significant educational, social, and economic costs for people and society. Functional neuroimaging research on schizophrenia physiopathology has been beneficial. Arterial spin labelling (ASL) is one of functional magnetic resonance imaging (fMRI) technologies that assess brain function without radiation. ASL uses magnetic resonance (MR) imaging to quantify tissue-level brain perfusion non-invasively. Arterial spin labelling (ASL) is one of the functional magnetic resonance imaging (fMRI) technologies that assess the brain function without radiation hazards. ASL uses magnetic resonance (MR) imaging to quantify tissue-level brain perfusion non-invasively. Many publications were performed on role of different advanced MRI techniques in schizophrenia, but our study insisted on the added value of combined ASL and MRS over the conventional MRI in schizophrenic Egyptian population sample.Aim of the workThe purpose of this work was to evaluate the added value of combined ASL-perfusion MRI and MRS in schizophrenic patients.MethodsThis prospective case–control study was carried out on two groups: First group was 30 patients who were diagnosed clinically as schizophrenic patients, and second group was 20 healthy volunteers as a control group for comparison in the period from August 2021 till July 2022.ResultsThe majority of newly diagnosed cases had significant higher positive symptoms than chronic cases. According to arterial spin labelling (ASL) data, rCBF was noticed to be reduced in anterior cingulate, frontal lobe, and parietal lobe of both patients’ subgroups but more significant in chronically ill patients. Convergent results of decreased rCBF were also found in the parietal lobe and occipital lobe. Magnetic resonance spectroscopic analysis showed that NAA was decreased in the anterior cingulate cortex, thalami and basal ganglia of the newly diagnosed cases more than chronic cases. The ASL-MRI perfusion accurately detected the hypo-perfusion of different brain regions with sensitivity 100%, specificity 66.67%, positive predictive value 96.43%, negative predictive value 100%, and accuracy 96.67%, while MR spectroscopy showed sensitivity 100%, specificity 33.33%, positive predictive value 93.10%, negative predictive value 100%, and accuracy 93.33% in evaluation of changes of brain metabolites.ConclusionASL is a promising functional MRI technique that can produce together with MRS quantitative information about the metabolites of different brain regions. The ASL-MRI appears as a reliable non-invasive technique to measure cerebral blood flow and identify decreased rCBF without any contrast administration, and it could be repeatable which helps in early diagnosis as well as follow-up of the progression of the disease.

Postoperative pain in oncological patients subjected to nonsurgical root canal treatment: a prospective case-control study.

The purpose of this prospective study was to evaluate the incidence and intensity of postoperative pain in oncological patients with infected teeth subjected to nonsurgical root canal treatment or retreatment. Teeth with apical periodontitis from healthy control patients and oncological patients (n = 70 per group) were root canal treated/retreated and evaluated for the development of postoperative pain. Patients from the two groups were matched for tooth type, gender, clinical manifestation of apical periodontitis, and intervention type. A visual analogue scale (VSA) was used to evaluate the incidence of postoperative pain at 24h, 72h, 7d, and 15d after chemomechanical procedures. Data were statistically analyzed for the incidence and intensity of postoperative pain in the two groups. Preoperative pain occurred in 10% of the individuals and in all these cases pain showed a reduction in intensity or was absent after endodontic intervention at 24-h evaluation. The overall incidence of postoperative pain at 24h was 14% in oncology patients and 30% in controls (p = 0.03). At 72h, the respective corresponding figures were 4% and 8.5% (p > 0.05). At 7 and 15 days, all patients were asymptomatic, irrespective of the group. No significant differences in postoperative pain were found between control and oncological patients. The low incidence of postoperative pain observed in both groups supports the routine use of nonsurgical root canal treatment/retreatment as valid options in oncological patients. Oncological patients had no increased risk of postoperative pain in comparison with control patients.

DNA repair efficiency in young hypertensive: Is lifestyle a prooxidant factor?

Background: High prevalence of hypertension (HTN) is of major concern among the middle-aged population of Kerala. Understudied in the context of HTN is oxidative damage to DNA, which is caused by free radical assaults. The modern lifestyle associated with an unhealthy diet and lack of exercise plays a key role in oxidative stress induction. Aims and Objectives: The objective of this study was to assess the significance of oxidative stress and the effectiveness of DNA repair mechanisms in young hypertensives along with how it correlates with aspects of lifestyle. Materials and Methods: This prospective case–control study enrolled clinically proven hypertensive patients referred from the outpatient department of Hridayalaya, Institute of Preventive Cardiology, Thiruvananthapuram, to Genetika, a research center for Cytogenetic Studies in South Kerala. Hypertensive patients (n=180) within the age group of 18–39 were compared with matched healthy controls (n=140). Associated lifestyle factors were determined. Results: In comparison to controls, cases had noticeably higher mean levels of malondialdehyde (MDA) and mean break per cell (P&lt;0.05). There was a difference that was statistically significant (P&lt;0.05) between the patients and controls in terms of diet, exercise, physical activity, obesity, mental stress, alcohol, and tobacco use. On comparing MDA and mean break per cell values with lifestyle factors, a statistically significant difference was detected (P&lt;0.05). Observed a significant positive correlation of break per cell value with MDA (P&lt;0.05). Conclusion: The current study demonstrated increased DNA damage and decreased DNA repair efficiency in young hypertensive and was strongly associated with lifestyle factors. Appropriate measures such as regular BP checkups, regular exercises, and abstinence from alcohol and smoking are to be taken for the prevention and control of HTN.

Bone conducted cervical vestibular evoked myogenic potentials: comparison of tone burst stimulus vs chirp stimulus.

Vestibular evoked myogenic potential (VEMP) is a test used to evaluate the function of otolith organs. In healthy individuals, air-conducted (AC) responses are obtained, whereas, in conductive hearing loss, the inability to transmit the signal well enough with AC stimuli has led to the need for bone-conducted (BC) stimuli. This study aimed to compare 500Hz Chirp and Tone Burst stimuli in terms of latency and amplitude in BC cVEMP. This prospective observational case control study included 35 healthy participants (70 ears) between the age of 20-50. Participants underwent VEMP testing with BC 500Hz Tone Burst stimulus and 500Hz narrow band Chirp stimulus without changing the position of the bone conducted vibrator. The intensity of the stimuli was 50 dB nHL. Response rate of 500Hz TB Stimulus was 51.4% and 95.7% in Chirp stimulus. It was observed that significantly more responses were obtained with Chirp stimulus than TB stimulus (p < 0.001). In terms of p1 latency, n1 latency, both latencies were significantly shorter in Chirp stimulus (p < 0.001). p1n1 amplitude was found significantly larger in Chirp stimulus (p < 0.001). Compared to 500Hz TB stimulus, 500Hz Chirp stimulus results in a higher response rate, larger p1n1 amplitude, and shorter p1 and n1 latency. A higher response rate may provide a more accurate assessment of otolith organs, reducing false negatives due to signal transmission in patients.

Presepsin in Human Milk Is Delivery Mode and Gender Dependent.

Breast milk (BM) is a unique food due to its nutritional composition and anti-inflammatory characteristics. Evidence has emerged on the role of Presepsin (PSEP) as a reliable marker of early sepsis diagnosis. In the present study, we aimed to investigate the measurability of PSEP in BM according to different maturation stages (colostrum, C; transition, Tr; and mature milks, Mt) and corrected for delivery mode and gender. We conducted a multicenter prospective case-control study in women who had delivered 22 term (T) and 22 preterm (PT) infants. A total of 44 human milk samples were collected and stored at -80 °C. BM PSEP (pg/mL) levels were measured by using a rapid chemiluminescent enzyme immunoassay. PSEP was detected in all samples analyzed. Higher (p < 0.05) BM PSEP concentrations were observed in the PT compared to the T infants. According to the grade of maturation, higher (p < 0.05) levels of PSEP in C compared to Tr and Mt milks were observed in the whole study population. The BM subtypes' degrees of maturation were delivery mode and gender dependent. We found that PSEP at high concentrations supports its antimicrobial action both in PT and T infants. These results open the door to further studies investigating the role of PSEP.

Cognitive dysfunction in older patients undergoing non-neurosurgery in the immediate postoperative period: A systematic review.

To explore the risk factors associated with postoperative cognitive dysfunction in older patients within the first 7 days after non-neurosurgical surgery and anaesthesia. A systematic review. Following, PRISMA 2020 (Preferred Reporting Items for Systematic Reviews and Meta-analyses). Checklist, a systematic review of studies published from January 2018 to January 2024. The literature search was conducted across six electronic online databases, including PubMed, EMBASE, Scopus, Ovid, MEDLINE and Science Direct, and the Johns Hopkins Nursing Evidence-Based Practice Evidence Rating Scale was used for study appraisal. The initial search yielded 1750 studies. The review included 19 studies which comprised prospective observational, case-control and retrospective studies. The prevalence of postoperative cognitive dysfunction ranged from 19% to 64% among older adults undergoing non-neurosurgery. The identified risk factors were classified into three phases including preoperative, intraoperative and postoperative. Preoperative risk factors were found in age, educational attainment, malnutrition, preoperative biomarkers and co-morbidities. Intraoperative risk factors were the duration of the operation, blood loss during the operation and anaesthesia used. Postoperative risk factors consisted of postoperative biomarkers and postoperative pain. The result from this review may assist researchers and healthcare providers in assessing the underlying causes and risk factors of postoperative cognitive dysfunction, and in formulating suitable preventative and therapeutic strategies for older adults with non-neurosurgery during the short-term postoperative period.

Re-exploration following caesarean birth: a prospective national case-control study using the United Kingdom Obstetric Surveillance System (UKOSS) data collection system.

Re-exploration following caesarean birth and the associated maternal morbidity has not been investigated in the UK. Our aims were to determine the national incidence and identify the associated risk factors. We conducted a prospective observational case-control study across 194 UK consultant-led maternity units in women whose caesarean birth was complicated by a re-exploration. Independent factors for re-exploration were analysed using multivariable multi-level mixed effects logistic regression. Over the study period (1 June 2021 and 31 May 2022) 238,423 caesarean births were recorded across the UK of which 187 women underwent re-exploration, giving an incidence of one re-exploration per 1282 caesarean births (95%CI 1:1099-1:1471). Haemorrhage (124/187, 66.3%) and sepsis (31/187, 16.6%) were the most common findings at re-exploration. Median (IQR [range]) time interval to re-exploration following the caesarean birth was 1 (0-4 [0-28]) day. Mechanical ventilation was required in 34 (18.6%) women, cardiac arrest was reported in 5 (2.7%) and 3 (1.6%) women died. Independent preceding factors associated with a re-exploration included: receipt of blood transfusion (adjusted OR (95%CI) 8.25 (2.66-25.61)); use of a general anaesthetic (adjusted OR (95%CI) 3.33 (1.61-6.88)); pre-eclampsia (adjusted OR (95%CI) 3.27 (1.55-6.91)); black ethnicity (adjusted OR (95%CI) 3.14 (1.39-7.11)); postpartum haemorrhage (adjusted OR (95%CI) 2.82 (1.81-4.37)); use of anticoagulants or antiplatelet drugs pre-caesarean birth (adjusted OR (95%CI) 2.26 (1.35-3.81)); and emergency caesarean birth (adjusted OR (95%CI) 1.89 (1.01-3.57)). Re-exploration following caesarean birth in the UK is uncommon but is associated with significant maternal morbidity and mortality. These study findings will help guide informed consent and encourage appropriate surveillance of high-risk women postpartum.

Value of serum muscular creatinine phosphokinase levels in patients with adenomyosis as a non-invasive diagnostic marker.

In the present study, we aimed to compare serum CK-MM levels in patients with and without adenomyosis and to investigate whether CK-MM level can be a non-invasive marker for myometrial damage due to adenomyosis. Our study was a prospective case-control study in a tertiary center and consisted of 40 patients with a clinical/ultrasonographic diagnosis of adenomyosis and 40 patients without a clinical/ultrasonographic diagnosis of adenomyosis as the control group based on recently published morphological uterus sonographic assessment (MUSA) criteria. Individuals of similar age who signed a voluntary consent form were included in our study. Demographic, clinical, and laboratory findings of the patients in both groups were recorded. Blood serum samples were used for the determination of serum CK-MM levels of the participants in our study. The samples were analyzed by using the human CK-MM enzyme-linked immunosorbent assay (ELISA) kit. In our study, the mean serum CK-MM level was 16.2 ± 21.7 (ng/dL) in patients with adenomyosis and 2.6 ± 2.2 (ng/dL) in patients without adenomyosis. Serum CK-MM level was statistically significantly higher in the patient group with adenomyosis than in the control group (p < 0.001). The CK-MM threshold value of 3.43 ng/mL, with a sensitivity of 82.5% and specificity of 85%, has been found to be a valuable distinguishing level in patients with and without adenomyosis. In this study, we demonstrated that serum CK-MM can be used as a non-invasive diagnostic method in patients with adenomyosis. As the number of studies around this subject in the literature is insufficient, larger studies are needed to use CK-MM as a diagnostic marker in adenomyosis.

The Neural Correlates of Central Auditory Dysfunction in Chronic Tinnitus: A Multimodal Approach.

It was aimed at assessing the connection between tinnitus and central auditory dysfunction using both central auditory tests (CATs) and diffusion tensor imaging (DTI) for brain regions that are crucial for central auditory processing. This prospective case-control study included 15 patients with persistent tinnitus and 20 healthy volunteers as controls. They underwent CATs for memory, attention, and DTI. The Tinnitus Handicap Inventory (THI) Questionnaire was applied as well. From several brain regions, the values of mean diffusivity (MD) and fractional anisotropy (FA) were determined. Comparing both groups, the tinnitus group showed statistically worse values as regards the CATs (memory for content, sequence memory, speech perception in noise (SPIN) at different signal-to-noise ratios, "SNRs") compared with the control group. As regards DTI, the tinnitus group showed decreased FA in several brain areas, including the cingulum, prefrontal-cortex (PFC), insula, and hippocampus. Furthermore, the tinnitus group showed significantly higher MD in the cingulum, BA-46, and amygdala compared with the control group. FA values of BA-46 were positively correlated with the SPIN-SNR-10 scores. Also, FA values of the middle cingulum were positively correlated with SPIN-SNRzero scores. MD values at BA-46 were negatively correlated with SPIN-SNR-10. THI scores were negatively correlated with FA at BA-46; however, they were positively correlated with MD at the amygdala. Central auditory dysfunction may be linked to the underlying neurophysiological changes in chronic tinnitus. Level 2 Laryngoscope, 2024.

A systematic review of sex and gender differences in treatment outcome of inflammatory skin diseases: Is it time for new guidelines?

Gender- and sex-specific differences in medicine were long-time disregarded. Despite numerous indications of gender- and sex-specific influences on the treatment of dermatological conditions, these have not yet been systematically investigated. To meet this unmet need, we conducted the present systematic review on the topic of gender and sex differences in the treatement outcome of skin diseases. Embase (via Ovid), PubMed Medline and Web of Science were searched, in between January 2001 and December 2022. English and german randomized controlled trials, prospective and retrospective cohorts and case-control studies that examined differences between men and women in treatment outcomes of skin diseases were included. Two authors independently screened the reports for eligibility, one extracted all data (the second double-checked) and critically appraised the quality and risk of bias of the studies. Eighty-three reports were included. The largest share of the identified publications focused on gender differences in psoriasis and psoriatic arthritis (n = 49), followed by melanoma (n = 8) and sporadic studies (n < 5) of inflammatory, infectious and autoimmune skin diseases. The main topics in which gender differences could be identified were choice of treatment, time to initiation of treatment, therapy response, adverse events, adherence and treatment satisfaction. For psoriasis, gender differences could be found in all aspects, while for the other skin diseases specific publications on gender differences are still missing. This systematic review shows numerous gender differences but also reveals major gaps in gender-specific care in dermatology which should be narrowed in the upcoming years to optimize a patient-centred, individualized, gender-equal healthcare. PROSPERO Registration: CRD42022306626.

Correlation between Serum Levels of HLA-G and Recurrent Implantation Failure During Implantation Window in Women Undergoing In Vitro Fertilization

Background: Recurrent implantation failure (RIF) during artificial reproductive techniques (ARTs) remains a health problem. Many physiopathological pathways have been proposed for RIF, but the causes are not yet clear. Thus, the purpose of the current study was to evaluate the possible correlation between human leucocyte antigen-G (HLA-G) serum levels and recurrent implantation failure during the implantation window in women undergoing In vitro fertilization (IVF). Materials and Methods: In this prospective case-control study, 39 patients with RIF and 20 cases with successful implantation were enrolled as the control group. HLA-G serum levels were measured using the sandwich ELISA method in both groups. Results: HLA-G serum levels in the RIF group were significantly higher than in controls (0.085 ± 0.019 compared to 0.073 ± 0.005, p = 0.024). Furthermore, by grouping patients based on age and BMI, we found that in the cases with ages above 30 years and with BMI more than 25 (kg/m2), HLA-G serum levels in the RIF group were remarkably greater than controls (0.088 ± 0.019 compared to 0.072 ± 0.004, p = 0.002 and 0.083 ± 0.012 compared to 0.072 ± 0.003, p = 0.021, respectively). Conclusion: Serum levels of HLA-G increase in the RIF patients, especially in cases of patients above 30 years old and those with BMI ≥ 25, which remains significant after eliminating confounding variables. These results may indicate the involvement of physiopathological pathways of HLA-G in the increasing risk of RIF.