Common Cause Research Articles

Profile of Blood Donors and Reasons for Deferral at a District Hospital in North Goa

Introduction: A blood transfusion is a life-sustaining procedure in several medical and surgical conditions. It isvital that an adequate inventory of safe blood is established by implementing stringent donor selection criteria andscreening for transfusion transmitted infections by ultrasensitive methods of detection. Despite a huge population,scarcity of blood lingers nationwide and it is important to analyse the varied reasons of deferrals in order to lessenthe deferrals in the future.The aim of this paper is to scrutinise the demographic profile of blood donors and evaluate the patterns andreasons for donor deferral at North Goa District hospital, India.Materials and Methods: This is a retrospective study carried out at the Blood Centre , North Goa Districthospital,India,. All those who registered for donation between June 2022 till May 2023 were included in the study.The donors were screened by a questionnaire followed by medical examination and were selected or deferredbased on the guidelines laid down by Drugs and Cosmetics Act,1940 and Directorate General of Health Services,MoHFW,Govt of India1.2 .Data was collected using a proforma and analysed by SPSS software wherever indicated.Results: During this time period, 2611 donors registered for blood donation, out of which 425 donors were deferreddue to diverse reasons. Most of the donors were voluntary donors(98.3%) of which majority were males(86.4%).The commonest cause of deferral in males was high BP(24%) and high Hb(11.3%) whereas the commonest cause ofdeferrals in females was low Hb (46.9%). Most of the donors were rejected due to temporary reasons(97.1%). Thecommonest reason of permanent deferrals was a medical history of uncontrolled DM.

A study to untangle the puzzle of urinary incontinence and frailty co-occurrence among older adults: The roles of depression and activity engagement.

To explore the co-occurrence of urinary incontinence and frailty by testing the roles of depression and activity engagement guided by the mechanisms of common cause and interaction pathways. A secondary analysis of a 1-year three-wave panel data collected from older nursing home residents in China. Changes in depression and activity engagement were regressed on urinary incontinence and frailty incidence underpinned by the common cause mechanism of chronic conditions co-occurrence, and these changes were also taken as mediators linking from frailty to urinary incontinence incidence supported by the interaction pathways' mechanism. A total of 348 older adults were included in this study, and 55.7% were women. The co-occurrence of urinary incontinence and frailty was found in 16.7% of the participants at baseline. Older adults with sole frailty at baseline had almost twice the rate of incident urinary incontinence (32.7%) compared with those without (16.7%) over a 1-year period. The subsample analyses showed that changes in depression and activity engagement failed to significantly predict the incidence of urinary incontinence and frailty. The mediating roles of these changes linking frailty to urinary incontinence incidence were also not statistically significant. The co-occurrence of urinary incontinence and frailty is prevalent in older nursing home residents. Older adults with frailty at baseline are more likely to develop urinary incontinence a year later. The common cause and interaction pathways mechanisms for the co-occurrence of urinary incontinence and frailty were not verified with changes in depression and activity engagement. The phenomenon of urinary incontinence and frailty co-occurrence should be given extreme emphasis. Although statistically significant findings on the roles of depression and activity engagement were not inferred, this study provides multiple possibilities for future studies to test and depict a clear picture of this co-occurrence. What problem did the study address? This study was designed to test the roles of depression and activity engagement in predicting the incidence of urinary incontinence and frailty, and the mediating roles in linking frailty to urinary incontinence incidence. What were the main findings? Despite the methodological pitfalls in literature have been addressed, neither depression nor activity engagement would significantly predict the incidence of urinary incontinence and frailty in older adults. Their mediating roles in linking frailty to urinary incontinence incidence were also not significant. Where and on whom will the research have an impact? Our findings add important pieces of evidence to promote researchers' understanding and provide an important basis for untangling the puzzle of urinary incontinence and frailty co-occurrence. The report of this study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement guidelines. No patient or public contribution.

Abstract 6145: A trans-ethnic meta-analysis identified additional novel genomic loci associated with cervical cancer

Abstract Introduction: Cervical cancer is the second most common cause of cancer-related deaths among women worldwide. Genome-wide association studies (GWAS) have identified genetic variants associated with cervical cancer. However, these discoveries have been limited by the small sample sizes of the individual cohorts. To identify additional novel loci associated with cervical cancer, we performed a trans-ethnic meta-analysis. Methods: GWAS summary data for trans-ethic meta-analysis were identified in women of European ancestry from the UK Biobank, East Asian ancestry from Biobank Japan, and African ancestries from the pan-UK Biobank and Johannesburg cancer study. Meta-analyses were performed using fixed effect inverse variance weighted method implemented in GWAMA. To localize putative genomic loci associated with cervical cancer, we performed fine mapping using the Bayesian approach by calculating the marginal posterior probability of causality for each single nucleotide polymorphisms (SNPs) and 99% credible set size. Results: Our meta-analysis identified four additional novel genomic loci associated with cervical cancer. These loci include: rs147778467 (odds ratio [OR] = 1.12, 95% confidence interval [CI] = 1.08-1.16, P-value = 3.12 x 10-08) in RGS21, rs53150478 (OR =1.03, 95%CI = 1.01-1.05, P-value = 4.48 x 10-08) in MAN1C1, rs113842373 (OR = 0.68, 95%CI = 0.56-0.81, P-value = 2.31 x 10-09) in LINCO1850 and rs75372437 (OR = 0.80, 95%CI = 0.72-0.88, P-value = 3.32 x 10-08) in RNU6-356P. These loci are implicated in carcinogenic pathways. Moreover, our Bayesian fine mapping identified five loci with a marginal posterior probability of causality > 1 and reduced the 99% credible set sizes. Conclusion: We identified additional novel loci associated with cervical cancer and our fine mapping identified loci with a high posterior probability of being causal. Citation Format: Abram Bunya Kamiza, Jean-Tristan Brandenburg, Michele Ramsay, Christopher Mathew. A trans-ethnic meta-analysis identified additional novel genomic loci associated with cervical cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6145.

Neoplasia detection in FIT positive screening colonoscopies compared with an age-controlled symptomatic cohort: a retrospective review

Colonoscopy following a positive FIT test in an average risk population is effective in reducing CRC incidence and mortality. While lower gastrointestinal symptoms remain a common cause for referral for colonoscopy, symptoms are poor predictors of clinically significant disease. The study was performed to compare neoplasia detection FIT +ve individuals and age-matched symptomatic cohorts. A single centre retrospective observational study was performed including all index colonoscopies performed on patients aged 60-70 from January 2015 to September 2021. Diagnostic yield was reported as adenoma detection rate, SSL detection rate, detection of high risk finding or adenocarcinoma. 8,106 colonoscopies were performed on patients aged 60-70 years. 3,695 (45.6%) originated from screening (FIT +ve). With exclusion criteria applied, 2,640 (59.9%) for screening and 1,767 (40.1%) for symptomatic patients were included. Median age in screening was 65 years (IQR 62-67) and 64 years in the symptomatic group (IQR 62-68), with male predominance in both groups (n=1,536, 58.1%, n=944, 53.4%). There were significant differences in both the ADR (56% vs 26.3%, p<0.01) and the SSLDR (10.4% vs. 8.1%, p=0.05) in the screening cohort compared to the symptomatic group. High risk findings (21.3% vs. 7.5%, p<0.01) were significantly more prevalent in the screening group with a considerably higher colorectal cancer (4.7% vs. 0.9%, p=<0.001) detection rate. FIT based triage significantly outperforms symptom based investigation for individuals in the 60-70 age group. Patients should be preferentially referred to organised colorectal cancer screening. FIT can be performed on symptomatic patients, to identify low risk individuals.

Abstract 3211: Development of first in class zip code drug conjugate in pancreatic ductal adenocarcinoma

Abstract Pancreatic ductal adenocarcinoma (PC) is the fourth most common cancer-related cause of death in Western countries. It is projected that PC will become the second most prevalent cause of cancer-related mortality by the year 2030. Although chemotherapy may offer certain advantages to those who have been diagnosed with pancreatic cancer, its effectiveness is notably constrained by the emergence of chemoresistance and excessive toxicity. In recent studies, it has been established that circulating tumor DNA (ctDNA) serves as a mechanism for cell-specific genetic transfer. We discovered that transposon sequences (known as Zip Codes, ZC) were responsible for ctDNA cell targeting. Therefore, we investigated the possibility of hijacking these ZC to deliver drugs specifically. We began by determining whether PDCA ZC synthesized chemically could target PDCA cells selectively. To achieve this, ZC sequences were labeled with CY5 for high-throughput microscopy. Results show that numerous PDCA-ZC were specific and efficient at targeting PC cell lines while sparing other cancer cell lines. The AluSc8 (PCZC) sequence was chosen for further investigation. The specificity of PCZC for targeting cells was validated using pancreatic islet cells. Based on these findings, we developed a technique for conjugating PCZC with SN38 via a CL2A linker. The results indicated that PCZC-SN38 was a very effective agent at killing PC cells (IC50: 1 μg), but not other cancer cell lines. The therapeutic efficacy of PCZC-N38 was evaluated in vivo using PDX (patient-derived xenografts, Garcia et al Plos One 2013). Maximum tolerated dose testing (MTD) (dosing from 1 to 21 mg of PCZC-SN38/Kg) failed to reach an MTD. Subsequently, we evaluated the efficacy signal of PCZC-SN38 by administering PCZC-SN38 to animals three times per week for three weeks at concentrations of 3 and 30 mg/kg of DNA (equivalent to 0.05 and 0.5 SN38 mg/kg). We used animals treated with vehicle, PCZC alone, and irinotecan (either once per week (50 mg/kg) or three times per week (0.5 mg/Kg) as a comparison. PCZC-SN38 decreased tumor growth by 41% and 70%, respectively, when compared to the vehicle or PCZC alone. The observed efficacy did not result in a change in body weight. In contrast, every animal administered irinotecan at a dosage of 50 mg/kg died within a week. On the contrary, animals that were given irinotecan at a dosage of 0.5 mg/kg demonstrated a growth inhibition of 60% and exhibited remarkable tolerability. Currently, research is being undertaken to determine the therapeutic efficacy of PCZC-SN38 at higher doses. The results outlined in this study illustrate the preliminary application of PC targeted drug delivery using a PC zip code drug conjugate. The results of our study demonstrate an innovative methodology for targeting PC cells specifically with therapeutic cargo material and supports further preclinical development of PCZC-SN38 for PC. Citation Format: Munnever Cinar, Purnachandra Ganji, Andrey Pisarev, Lourdes Martinez-Medina, Dhana S. Bandi, Pavan K. Puvvula, Steven Chang, Daniel Maneval, Bassel El-Rayes, Leon Bernal-Mizrachi. Development of first in class zip code drug conjugate in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3211.

Breastfeeding and fatty liver - is there any association?

The campaign to promote the natural feeding of infants, at least for the first six months of life, conducted over recent years has deep justification from a medical point of view. Numerous gynecological and pediatric societies around the world recommend breastfeeding as the most appropriate way of feeding infants. It has been proven that the benefits of this type of nutrition go beyond nutritional aspects, proper growth and development. The list of long-term metabolic benefits, which include reducing the incidence of obesity, allergies, infections and diabetes, is constantly growing. It has been shown that the method of feeding infants using various mechanisms may influence the tendency of the liver to accumulate fatty compounds and develop fatty liver disease with its metabolic consequences leading to liver failure, cirrhosis and hepatocellular carcinoma. This is an important discovery due to the growing obesity epidemic in adults and children. Metabolic dysfunction - associated fatty liver disease (MAFLD) has become the most common cause of chronic liver disease, affecting 25% of the global population. The results of studies conducted in recent years have shown the protective effect of breastfeeding on the risk of developing MAFLD later in life in both children and breastfeeding women. New scientific reports provide the basis for qualifying breastfeeding as a modifiable risk factor for MAFLD.

The Effect of Apathy and Depressive Syndromes on Functional Outcomes in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common cause of dementia. Its initially characterized by progressive short-term memory loss followed by cross-domain cognitive decline in later stages resulting in significant functional deficits and loss of activities of daily living (ADLs) independence. Apathy and depression are frequent neuropsychiatric sequelae in AD, but their contribution to functional deficits is poorly understood. We aimed to quantitatively investigate if apathy and depressive symptoms predict ADLs in AD. We also wanted to fractionate apathy dimensions by factor-analyzing the apathy evaluation scale (AES) and then investigate the dimensions' relation to ADLs. We recruited a sample of 115 patients with probable or possible AD and assessed them for depression, apathy, and ADLs alongside other measures. We hypothesized that apathy and depressive symptoms would predict ADLs and that AES items will load into cognitive, behavioral, and affective factors that would differentially relate to ADLs. Our results indicated that apathy symptoms predict ADLs deficits. The AES items resolved into a three-factor solution but the manner of clustering diverged from that proposed by AES authors. When these factors were regressed simultaneously, only behavioral apathy predicted global ADLs. Distinguishing basic from instrumental ADLs showed that behavioral and cognitive apathy symptoms associate with ADLs deficits while affective symptoms do not. Our results highlight the influence of apathy on ADLs in AD. This has important implications for patient care considering the high prevalence of apathy in AD and other dementing illnesses.

Pediatric Cases Diagnosed with Drug-Related Acute Tubulointerstitial Nephritis: A Single-Center Experience

Aim: Acute tubulointerstitial nephritis (TIN) is inflammation of the renal interstitium. It is also a common cause of acute kidney injury (AKI). The aim is to contribute to the literature by evaluating patients diagnosed with drug-induced TIN.
 Material methods: 29 Turkish children aged between 3 and 217 months, 5 of whom had undergone a biopsy, were retrospectively analyzed in terms of clinical and laboratory findings.
 Results: 29 patients, 19 of whom were girls, were evaluated. The mean age at diagnosis was 138.6(3-217) ± 67.4 months. Nausea-vomiting complaint of 12 cases, 6 under treatment during hospitalization, 4 with headache, 2 with isolated fatigue, and the remaining 5 patients with incidentally detected renal function test disorder, oligo-anuria, urinary incontinence, red urination, and uveitis. At the time of diagnosis, 4 patients had hypertension and 26 patients had AKI. Two of these cases were anuric. The low eGFR values at the time of diagnosis were observed to improve at the end of the follow-up. Hematuria was detected in 18 cases and of them were macroscopic hematuria. 4 patients had pyuria, 19 patients had proteinuria, and 2 of them were nephrotic. FeNa was the most common abnormality of the tubular tests with 4.5%. Biopsy was performed in 5 cases. While one of the patients presented with uveitis, uveitis developed in 1 patient during the 3rd month of follow-up.
 Conclusion: Consequently, although TIN is a reversible disease, its recognition is important in terms of treatment and follow-up.

Community Preferences for the Care of Older People at the End of Life: How Important is the Disease Context?

Population preferences for care at the end of life can inform palliative care policy and direction. Research investigating preferences for care at the end of life has focused predominantly on the context of advanced cancer, with relatively little attention to other life-limiting illnesses that are common causes of death. We aimed to investigate preferences for the care of older people at the end of life in three different disease contexts. The purpose was to understand if population preferences for care in the last 3 weeks of life would differ for patients dying from cancer, heart failure or dementia. Three discrete choice experiments were conducted in Australia with a general population sample using similar methods but different end-of-life disease contexts. Some attributes were common across the three experiments and others differed to accommodate the specific disease context. Each survey was completed by a different panel sample aged ≥45years (cancer, n=1548; dementia, n=1549; heart failure, n=1003). Analysis was by separate mixed logit models. The most important attributes across all three surveys were costs to the patient and family, patient symptoms and informal carer stress. The probability of choosing an alternative was lowest (0.18-0.29) when any one of these attributes was at the least favourable level, holding other attributes constant across alternatives. The cancer survey explored symptoms more specifically and found patient anxiety with a higher relative importance score than the symptom attribute of pain. Dementia was the only context where most respondents preferred to not have a medical intervention to prolong life; the probability of choosing an alternative with a feeding tube was 0.40 (95% confidence interval 0.36-0.43). This study suggests a need for affordable services that focus on improving patient and carer well-being irrespective of the location of care, and this message is consistent across different disease contexts, including cancer, heart failure and dementia. It also suggests some different considerations in the context of people dying from dementia where medical intervention to prolong life was less desirable.

Incidental but Not Insignificant: Thyroid Cancer in Patients with Graves Disease.

Graves disease is the most common cause of hyperthyroidism in the US. Treatment with antithyroid drugs and radioactive iodine is more commonly used than surgical management with total thyroidectomy (TTx). However, incidentally discovered thyroid cancer (TC) has been described on surgical pathology from patients who underwent surgical treatment of Graves disease, which would be missed with these other treatment strategies. We sought to determine the incidence rate of TC among patients with surgically treated Graves disease. We retrospectively reviewed patients with Graves disease who underwent TTx at a single institution from 2011 to 2023. Pathology reports were reviewed for TC. Patient demographics, preoperative laboratory and radiological evaluations, preoperative medical management, and surgical outcomes were compared between patients with and without incidental TC. There were 934 patients, of whom 60 (6.4%) patients had incidentally discovered TC on pathology. The majority (58.3%) of patients had papillary thyroid carcinoma, followed by 33.3% with papillary microcarcinoma. Preoperative ultrasound (US) was obtained in 564 (60.4%) of patients, with 44.3% with nodules, but only 34 (13.7%) of those with nodules had TC on final pathology. Preoperative fine needle aspiration was obtained in 15 patients with TC, and 8 patients (53.3%) were reported as benign lesions, which ultimately had TC on final pathology. There was no difference in sex, race or ethnicity, preoperative medical management, and postoperative outcomes between the 2 groups. Incidental TC was found on surgical pathology in 6.4% of patients undergoing TTx for Graves disease. Preoperative imaging with US and fine needle aspiration were often unreliable at predicting TC. The incidence of TC should not be underestimated when counseling patients on definitive management for Graves disease.

Management of outpatient pediatric burns at a pediatric burn center.

Burn injuries are a serious emergency. Most burn injuries in children can be treated as outpatients. The aim of this study was to present the clinical and epidemiologic characteristics of pediatric burn injuries treated in our outpatient burn clinic. This study included pediatric patients treated in an outpatient burn clinic over an eight-year period. The demographic and clinical characteristics of the patients were retrospectively analyzed. The patients were divided into four groups according to their age groups, and the differences between the groups were investigated. Statistical analysis was performed using IBM SPSS Statistics, Version 25.0. P<0.05 was accepted as statistically significant. Of the total 5,167 patients, 2,811 (54.4%) were male. Scald burns were the most common cause of burns (81.4%). Contact burns accounted for 12.2% of all burns. There were no differences between sexes for any variable. The highest incidence was seen in children in the 2-5-year-old age group (28.3%). There were differences between age groups in terms of sex, burn area, burn visit, burn type, burn location, need for wound dressing under anesthesia, and need for grafting. Among the patients, 4.9% were hospitalized due to the need for wound dressing under anesthesia. However, most of the patients (95.1%) were treated as outpatients. In conclusion, the majority of pediatric burn patients can be treated as outpatients. This allows pediatric patients to complete treatment in a psychologically comfortable environment and have low complication rates. Outpatient treatment should become the standard for children who are suitable for outpatient follow-up and who have home support.

Deep learning-based automated lesion segmentation on pediatric focal cortical dysplasia II preoperative MRI: a reliable approach

ObjectivesFocal cortical dysplasia (FCD) represents one of the most common causes of refractory epilepsy in children. Deep learning demonstrates great power in tissue discrimination by analyzing MRI data. A prediction model was built and verified using 3D full-resolution nnU-Net for automatic lesion detection and segmentation of children with FCD II.MethodsHigh-resolution brain MRI structure data from 65 patients, confirmed with FCD II by pathology, were retrospectively studied. Experienced neuroradiologists segmented and labeled the lesions as the ground truth. Also, we used 3D full-resolution nnU-Net to segment lesions automatically, generating detection maps. The algorithm was trained using fivefold cross-validation, with data partitioned into training (N = 200) and testing (N = 15). To evaluate performance, detection maps were compared to expert manual labels. The Dice-Sørensen coefficient (DSC) and sensitivity were used to assess the algorithm performance.ResultsThe 3D nnU-Net showed a good performance for FCD lesion detection at the voxel level, with a sensitivity of 0.73. The best segmentation model achieved a mean DSC score of 0.57 on the testing dataset.ConclusionThis pilot study confirmed that 3D full-resolution nnU-Net can automatically segment FCD lesions with reliable outcomes. This provides a novel approach to FCD lesion detection.Critical relevance statementOur fully automatic models could process the 3D T1-MPRAGE data and segment FCD II lesions with reliable outcomes.Key points• Simplified image processing promotes the DL model implemented in clinical practice.• The histopathological confirmed lesion masks enhance the clinical credibility of the AI model.• The voxel-level evaluation metrics benefit lesion detection and clinical decisions.Graphical

Trend and Determinants of Neonatal Mortality at the Buea and Limbe Regional Hospitals, Southwest Region, Cameroon

Background: Over the years the rate of neonatal mortality in low-income settings has been on the increase and most cases of neonatal mortality can be associated with modifiable risk factors. However, the rate of neonatal mortality remains high in Cameroon with the Southwest Region having one of the highest rates of neonatal mortality. Objectives: We aimed to determine the trend and determinants of neonatal mortality in Buea and Limbe Regional Hospitals. Method and Materials: A hospital based retrospective study of files of neonates was conducted from the 1st of January 2017 to the 31st of December 2022. Socio-demographic, clinical and outcome data were obtained using a data extraction form and analyzed using Statistical Package for Social Science (SPSS) Version 27. Results: The trend of neonatal mortality was apparently constant (16.1% and 17.8%) between 2017 to 2022. Birth asphyxia 150(53.4%) was found to be the most common cause of neonatal mortality. Identified determinants were: acute fetal distress (AOR:2.6 [1.333-5.346]), no ANC visit (AOR:13.1 [3.849-44.284]), birth weight less than 2500g (AOR:2.050 [0.039-4.216]), birth weight greater than 4000 g (AOR:2 [1.002-3.43]), Apgar Score ˂ 3 (AOR:99.9 [87.036-100.000]) and Apgar score ˂ 6 (AOR=5.164 [1.768-15.082]). Conclusion: Neonatal mortality in our context is still below the expectations of SDG3 with perinatal asphyxia and its related modifiable factors influencing neonatal mortality the most. Therefore, more impactful community education and information sessions to build a positive mind set on pregnant women and their families to reduce neonatal mortality is required from all health sectors.

Central retinal artery occlusion after cardioversion of atrial fibrillation.

Central retinal artery occlusion (CRAO) is a vascular ophthalmic emergency. Often caused by a sudden interruption of blood flow to the eye, with profound and painless vision loss, resulting in irreversible cell damage. An impacted embolus at the narrowest part of the central retinal artery is the most common cause. Cardioversion is a medical procedure used to restore a normal heart rhythm in individuals with atrial fibrillation (AF). In some cases, cardioversion can lead to thromboembolic complications. If an embolus reaches the central retinal artery, it can block the blood flow to the retina, resulting in CRAO and subsequent vision loss.

Distinct patterns of postoperative fever in paediatric neurosurgery patients.

Postoperative fever is a common problem following neurosurgery but data on the causes among paediatric patients is sparse. In this report, we determined the incidence, causes, and outcomes of postoperative fever in paediatric neurosurgical patients (< 18years), and contrasted the findings with an adult cohort published recently from our unit. We recruited 61 patients who underwent 73 surgeries for non-traumatic neurosurgical indications over 12months. A standard protocol was followed for the evaluation and management of postoperative fever. We prospectively collected data pertaining to operative details, daily maximal temperature, clinical features, and use of surgical drains, urinary catheters, and other adjuncts. Elevated body temperature of > 99.9 °F or 37.7°C for > 48h or associated with clinical deterioration or localising features was considered as "fever"; elevated temperature not meeting these criteria was classified as transient elevation in temperature (TET). Twenty-six patients (35.6%) had postoperative fever, more frequent than in adult patients. TET occurred in 12 patients (16.4%). The most common causes of fever were aseptic meningitis (34.6%), followed by urinary tract infections (15.4%), pyogenic meningitis, COVID-19, and wound infections. Postoperative fever was associated with significantly longer duration of hospital admission and was the commonest cause of readmission. In contrast to adults, early temperature elevations in paediatric patients may portend infectious and serious non-infectious causes of fever, including delayed presentation with aseptic meningitis, a novel association among paediatric patients. Investigation guided by clinical assessment and conservative antibiotic policy in keeping with the institutional microbiological profile provides the most appropriate strategy in managing paediatric postoperative fever.

Long term clinical follow up of four patients with Wolfram syndrome and urodynamic abnormalities.

Wolfram syndrome is characterised by insulin-dependent diabetes (IDDM), diabetes insipidus (DI), optic atrophy, sensorineural deafness and neurocognitive disorders. The DIDMOAD acronym has been recently modified to DIDMOAUD suggesting the rising awareness of the prevalence of urinary tract dysfunction (UD). End stage renal disease is the commonest cause of mortality in Wolfram syndrome. We present a case series with main objective of long term follow up in four children having Wolfram syndrome with evaluation of their urodynamic profile. A prospective follow up of four genetically proven children with Wolfram syndrome presenting to a tertiary care pediatric diabetes clinic in Pune, India was conducted. Their clinical, and urodynamic parameters were reviewed. IDDM, in the first decade, was the initial presentation in all the four children (three male and one female). Three children had persistent polyuria and polydipsia despite having optimum glycemic control; hence were diagnosed to have DI and treated with desmopressin. All four patients entered spontaneous puberty. All patients had homozygous mutation in WFS1 gene; three with exon 8 and one with exon 6 novel mutations. These children with symptoms of lower urinary tract malfunction were further evaluated with urodynamic studies; two of them had hypocontractile detrusor and another had sphincter-detrusor dyssynergia. Patients with hypocontractile bladder were taught clean intermittent catheterization and the use of overnight drain. We report a novel homozygous deletion in exon 6 of WFS-1 gene. The importance of evaluation of lower urinary tract malfunction is highlighted by our case series. The final bladder outcome in our cases was a poorly contractile bladder in three patients.

The Outcomes of Emergency Admissions and Associated Factors Among Children Admitted to the Pediatric Emergency Unit at Selected Public Hospitals in Addis Ababa, Ethiopia — A Retrospective Cross-Sectional Study

BACKGROUND: A pediatric emergency condition is a life-threatening process that, without timely and standard clinical intervention, may lead to death. Therefore, this study aimed to assess the outcomes of emergency admissions and associated factors among children admitted to the pediatric emergency of selected public hospitals. METHODS: An institutional-based retrospective cross-sectional study design was conducted on children admitted to the emergency unit/ward from January 02, 2020, to January 08, 2022, in the emergency units of randomly selected public hospitals. Data were extracted with prepared checklists from February 1 to March 1, 2022. RESULT: A total of 303 admitted children’s charts were reviewed with 100% coverage. The mean age of children was 37.47 months, and the male-to-female ratio was 1.16:1. The study revealed that the most common causes of emergency admission were pneumonia (22.4%), surgical emergencies (14.5%), and late-onset sepsis (9.2%), respectively. More than half (53.8%) of children were admitted to the Pediatric Emergency Department for less than 24 hours, and the mean length of stay was 2 days. 39.6% of children were discharged with clinical improvement. Known comorbidity (AOR=4.65, 95% CI (1.23-17.64)) and length of stay less than 24 hours (AOR=4.2, 95% CI (1.2-14.7)) were strongly associated with the outcome. CONCLUSION: Pneumonia is still the most common cause of pediatric emergency admission, and the mortality rate of children at the Pediatric Emergency Department is high, with known comorbidity showing a significant association with mortality. FMOH recommended developing national pediatric emergency care guidelines and providing skill gap training for healthcare workers.

Role Played by Biochemical and Hematological Parameters in the Prediction of Cardiovascular Risk

Introduction: The term “cardiovascular diseases” (CVDs) refers to any disease affecting the heart or blood vessels. CVDs are the most common cause of death worldwide and the most responsible reason for 10% of deaths in the early 20th century. These CVDs can emerge as myocardial infarction or ischemic heart disease, stroke, and congestive heart failure. For diagnosing CVDs, physical, radiological investigations, and laboratory investigations for cardiac enzymes and lipid profile are used. In clinical practices, cardiovascular risk prediction models are very important in the identification, prevention, and staging of the severity of CVDs. Framingham Risk Score-coronary heart disease, Framingham Risk Score-cardiovascular disease, QRESEARCH-cardiovascular risk algorithm, Joint British Society risk-calculator-3, WHO/ISH CVD risk prediction charts, and Atherosclerotic Cardiovascular Disease risk-estimator are some of the available CVD risk estimators. However, many of these estimators can be used only to evaluate individuals more than 40 years and to assess the risk for 10-years. Therefore, new risk estimators are needed to overcome the deficiencies of the available risk estimators. Research have been done in novel directions; on ratios of routinely performing hematological and biochemical laboratory parameters such as Neutrophil to Lymphocyte Ratio (NLR), Platelet to Lymphocyte Ratio (PLR), and Aspartate aminotransferase to Alanine aminotransferase ratio (AST/ALT). The outcomes indicate a relationship between the above-said ratios and the risk for CVDs. &#x0D; Conclusion: On such grounds, this review describes the importance of developing a CVD risk estimator by amalgamating some of the biochemical and hematological parameters, including NLR, PLR, and AST/ALT ratios, aiming to overcome the existing shortcomings.

Effective treatment of Clostridioides difficile infection improves survival and affects graft-versus-host disease: a multicenter study by the Polish Adult Leukemia Group

Clostridioides difficile infection (CDI) is the most common cause of infectious diarrhea after allogeneic hematopoietic cell transplantation (allo-HCT). The impact of CDI and its treatment on allo-HCT outcomes and graft-versus-host disease (GVHD), including gastrointestinal GVHD (GI-GVHD) is not well established. This multicenter study assessed real-life data on the first-line treatment of CDI and its impact on allo-HCT outcomes. Retrospective and prospective data of patients with CDI after allo-HCT were assessed. We noted statistically significant increase in the incidence of acute GVHD and acute GI-GVHD after CDI (P = 0.005 and P = 0.016, respectively). The first-line treatment for CDI included metronidazole in 34 patients, vancomycin in 64, and combination therapy in 10. Treatment failure was more common with metronidazole than vancomycin (38.2% vs. 6.2%; P < 0.001). The need to administer second-line treatment was associated with the occurrence or exacerbation of GVHD (P < 0.05) and GI-GVHD (P < 0.001) and reduced overall survival (P < 0.05). In the multivariate analysis, the risk of death was associated with acute GVHD presence before CDI (hazard ratio [HR], 3.19; P = 0.009) and the need to switch to second-line treatment (HR, 4.83; P < 0.001). The efficacy of the initial CDI treatment affects survival and occurrence of immune-mediated GI-GVHD after allo-HCT. Therefore, agents with higher efficacy than metronidazole (vancomycin or fidaxomicin) should be administered as the first-line treatment.

Notoginsenoside R1 alleviates cerebral ischemia/reperfusion injury by inhibiting the TLR4/MyD88/NF-κB signaling pathway through microbiota-gut-brain axis

BackgroundIschemic stroke (IS) ranks as the second common cause of death worldwide. However, a narrow thrombolysis timeframe and ischemia-reperfusion (I/R) injury limits patient recovery. Moreover, anticoagulation and antithrombotic drugs do not meet the clinical requirements. Studies have demonstrated close communication between the brain and gut microbiota in IS. Notoginsenoside R1 (NG-R1), a significant component of the total saponins from Panax notoginseng, has been demonstrated to be effective against cerebral I/R injury. Total saponins have been used to treat IS in Chinese pharmacopoeia. Furthermore, previous research has indicated that the absorption of NG-R1 was controlled by gut microbiota. Study designThis study aimed to access the impact of NG-R1 treatment on neuroinflammation and investigate the microbiota-related mechanisms. ResultsNG-R1 significantly reduced neuronal death and neuroinflammation in middle cerebral artery occlusion/reperfusion (MCAO/R) models. 16S rRNA sequencing revealed that NG-R1 treatment displayed the reversal of microbiota related with MCAO/R models. Additionally, NG-R1 administration attenuated intestinal inflammation, gut barrier destruction, and systemic inflammation. Furthermore, microbiota transplantation from NG-R1 exhibited a similar effect in the MCAO/R models. ConclusionIn summary, NG-R1 treatment resulted in the restoration of the structure of the blood-brain barrier (BBB) and reduction in neuroinflammation via suppressing the stimulation of astrocytes and microglia in the cerebral ischemic area. Mechanistic research demonstrated that NG-R1 treatment suppressed the toll-like receptor 4/myeloid differentiation primary response 88/nuclear factor kappa B (TLR4/MyD88/NF-κB) signaling pathway in both the ischemic brain and colon. NG-R1 treatment enhanced microbiota dysbiosis by inhibiting the TLR4 signaling pathway to protect MCAO/R models. These findings elucidate the mechanisms by which NG-R1 improve stroke outcomes and provide some basis for Panax notoginseng saponins in clinical treatment.