Late Onset Research Articles

Myxomatous mitral valve disease in Labrador Retrievers and Golden Retrievers.

To characterize myxomatous mitral valve disease (MMVD) in Labrador Retrievers (LRs) and Golden Retrievers (GRs). 52 LRs and 20 GRs diagnosed with MMVD composed a retrospective study sample (February 1, 2010, to July 31, 2021). Stored echocardiograms were remeasured. Dogs were staged by 2019 MMVD consensus guidelines. Mean age was 9.9 years in LRs and 9.5 years in GRs, with 31 of 52 LRs (59.6%) and 13 of 20 (65.0%) GRs being male. Forty-six LRs were stage B1 (88.5%), 3 were B2 (5.8%), and 3 were C (5.8%). Fourteen GRs were stage B1 (70.0%), 2 were B2 (10.0%), and 4 were C (20.0%). Of LRs and GRs in stage B2/C, 50% had systolic dysfunction. Atrial fibrillation (AF) and ventricular arrhythmias were identified in 2 of 52 (3.8%) and 10 of 52 (19.2%) LRs at initial diagnosis versus 3 of 20 (15.0%) and 3 of 20 (15.0%) GRs, respectively. All 5 AF dogs were stage C, with intermediate to high probability of pulmonary hypertension. Two additional GRs developed AF during follow-up; thus 5 of 6 (83.3%) stage B2/C GRs ultimately experienced AF. Subjective mitral valve thickening was frequent in both breeds (41/52 LRs [78.8%]; 18/20 GRs [90.0%]), while mitral valve prolapse was more common in LRs (22/52 [42.3%]) than GRs (5/20 [25.0%]). In LRs and GRs, MMVD was relatively late onset, with males overrepresented. Both breeds exhibited mitral valve thickening in association with MMVD, while LRs more commonly exhibited mitral valve prolapse. While most LRs and GRs with MMVD were stage B1, those in stage B2/C had increased prevalence of systolic dysfunction and AF.

Hereditary transthyretin amyloidosis caused by Val142Ile variant in Spain: phenotypic characteristics, geographic distribution and population frequency

Abstract Background During recent years, several cases of hereditary transthyretin amyloidosis (ATTRv) due to p.Val142Ile have been described in patients without African ancestry in countries like Japan, Spain or Italy (1,2,3,4). All this evidence suggests that p.Val142Ile might be more prevalent than expected worldwide. Objectives The aim of this study was to analyze the impact of ATTRv caused p.Val142Ile in Spain to define its phenotypic characteristics, to explore endemic geographical areas and define its population frequency. Methods Patients diagnosed with ATTRv caused by p.Val142Ile and carriers irrespective of their phenotype were recruited from 16 centers in Spain. Baseline characteristics and events during follow-up were retrieved. Population frequency was assessed through the Spanish National DNA bank (N=3,569) and the Catalan Health Databank (N=790). Results The cohort included information regarding 164 subjects (75 probands [45.7%] and 89 relatives [54.3%]). Among probands, mean age was 73.9 ± 8.5 years and 47 (62.7%) were males. 67 probands (89.3%) had self-declared European ancestry and only 6 cases (8%) referred African or Afro-American ancestry. Cardiac symptoms were the most frequent reason leading to ATTRv diagnosis (N=64, 85.3%) followed by incidental finding (N=8, 10.7%) and neurologic symptoms (N=3, 4%). (Figure 1). Median follow-up was 1.6 years (Interquartile range 0.6-3.2). Neurologic involvement was observed in 35 probands (46.7%) at first evaluation or during follow-up. Overall penetrance at 65, 75 and 85 years was 12.8%, 44.3% and 94.2% respectively. Male sex was associated with earlier penetrance than women (P = 0.02). 38 patients initiated treatment with tafamidis during follow-up (28 [73.7%] 20 mg and 10 [26.3%] 61 mg), despite treatment, disease progression at 1 year (cardiovascular death or 30% increase of NTProBNP) was observed in 10 patients (40%). Population frequency was estimated between 0.0% and 0.12% based on the Spanish and Catalan databases respectively. Birthplace of probands suggests a higher prevalence in the Mediterranean basin. (Figure 2) Conclusions Our data suggests that ATTRv caused by p.Val142Ile has a significant prevalence in Spain, mostly in some specific regions. Phenotypic features are defined by late onset, male predominance, and cardiac involvement although a significant proportion develop neuropathy. Disease progression was observed in 40% of patients despite disease-modifying therapies.

Intracranial inoculation rapidly induces Nipah virus encephalitis in Syrian hamsters.

Nipah virus (NiV) is a highly pathogenic Paramyxovirus associated with outbreaks in Malaysia, Bangladesh, and India with high mortality rates. NiV infection causes fatal respiratory and neurological disease. The majority of survivors suffer from long-term neurological sequelae or late onset and relapsed encephalitis. The pathogenesis of neurological disease is complex and has not been able to be studied in current animal models as they are skewed towards the development of lethal respiratory disease rather than neurological disease. Although NiV neurological disease can be observed in animal models, there is currently no model where the majority of animals consistently develop neurological disease. Here, we developed a new Syrian hamster (Mesocricetus auratus) model to mimic neurological disease in humans. Hamsters were inoculated intracranially in the cerebellomedullary cistern with different doses of NiV, strain Malaysia. Intracranial NiV inoculation in the cerebellomedullary cistern resulted in a rapid progression towards severe neurological disease requiring euthanasia. High Nipah viral loads were detected in the brains, and NiV spread from the CNS to the lungs. Histopathologic examination of the brain showed ischemic necrosis, often accompanied by marked edema and hemorrhage. NiV antigen was detected primarily in meninges and cerebellum, but rarely observed in brain parenchyma. These histological lesions were different from the typical lesions observed in NiV-infected humans. Thus, despite the consistent development of neurological disease, intracranial inoculation does not result in a model representative of NiV neurological disease.

The Good (Tumor Killing) and the Bad (Cardiovascular Complications) of Immunologic Checkpoint Inhibitors.

This review details the significant advancement in knowledge of Immune-checkpoint inhibitor (ICI) and its potential deleterious cardiac immune-related adverse effects (irAE). We explore their mechanisms on the cardiac tissue, providing guidance on risk factors, clinical presentations, diagnostic strategies along with treatment. Recent findings have provided insights of cardiac irAEs that exist beyond the previously well-known ICI-induced myocarditis. We have a better understanding of the wide variety of cardiac irAEs pathologies both early and late onset. Moreover, there is more data on mechanisms of cardiotoxicity and patient and therapy-related risk factors, supporting closer routine cardiac monitoring with biomarkers and imaging for prevention and early detection. Diagnosing cardiac irAEs is a challenge given its broad clinical presentation. A high-level of suspicion in addition to early work-up is crucial to prevent serious cardiac events. A multi-disciplinary team including Cardiologists and Oncologists is essential for closely monitor patients' cardiac status on ICI therapy. There is a need of updated guidelines to establish clear recommendations in patients on ICIs.

Long-Term Risk of Medication-Related Osteonecrosis of the Jaw (MRONJ) After Bisphosphonates and/or Denosumab in Metastatic Breast Cancer Patients

Recently published data identified cancer patients with bone metastases receiving continuous monthly antiresorptive drugs (bisphosphonates and/or denosumab) as patients at high risk for Medication-Related Osteonecrosis of the Jaw (MRONJ), even with late onset. A retrospective multicenter study was conducted between 2000 and 2020 at all breast centers across Tyrol (Austria), screening all patients with breast cancer and bone metastases receiving antiresorptive therapy. The MRONJ incidence was found to be considerably high in patients receiving denosumab (11.6%-16.3%), with an elevated cumulative incidence at 6 years. This commentary underlines some important results of the study and proposes further evaluation of the group of patients receiving a sequence of bisphosphonates and denosumab. Furthermore, other interesting data could come from patients treated in the last decade, receiving more effective anticancer treatments but also more frequently denosumab, in comparison with patients treated in previous years.

LATE ONSET PSYCHOSIS IN THE ELDERLY

Late-onset psychosis in the elderly is a condition characterized by the onset of psychotic symptoms, such as hallucinations and delusions, after the age of 60. Although psychosis at younger ages is often associated with primary psychiatric disorders such as schizophrenia, diagnosis in the elderly is more complex, as it involves the need to differentiate between various conditions that can affect the brain and behavior, such as dementias, neurological disorders and factors related to brain aging. The impact of brain aging, such as diminished cognitive abilities and changes in brain structure, also plays an important role in the development and course of psychosis in this age group. The aim of this work is to analyze the differential diagnosis of late onset psychosis in the elderly, exploring the conditions that can mimic psychotic symptoms and the impact of brain aging on this process. It also aims to assess the implications of this diagnosis for clinical management and patients’ quality of life. This study uses a systematic review to investigate late onset psychosis in the elderly, its relationship with neurodegenerative diseases, differential diagnoses with dementias and therapeutic approaches, both pharmacological and non-pharmacological. The search was carried out in databases such as SciELO, PubMed, LILACS and Journal of Neurosciences, and included analysis of critical reviews, empirical studies and clinical guidelines. Additional data was obtained from population studies and clinical analyses involving geriatric patients with psychosis. The differential diagnosis of late onset psychosis is challenging, as it involves distinguishing between primary and secondary psychiatric causes. Neurodegenerative disorders, such as Alzheimer’s disease and dementia with Lewy bodies, are often associated with psychotic symptoms in the elderly. Likewise, disorders such as major depression with psychotic features and delirium can present with similar symptoms, and a detailed clinical assessment is essential. The exclusion of underlying medical factors, such as infections, metabolic disorders and adverse effects of medication, is crucial to ensure an accurate diagnosis. Brain aging, in turn, plays a key role in the vulnerability of the elderly to psychosis. With age, structural and functional changes occur in the brain, such as cortical atrophy, reduced neuronal density and alterations in dopaminergic pathways, which can predispose to the emergence of psychotic symptoms. These changes make the brain more susceptible to stress factors, inflammation and sensory deficits, which can precipitate psychotic episodes. Thus, the treatment of late onset psychosis involves a careful approach, given the sensitivity of the elderly to antipsychotics and the increased risk of side effects. The choice of treatment must balance efficacy in controlling symptoms with minimizing risks, and the use of low doses and constant monitoring are recommended to avoid complications. It is therefore concluded that late onset psychosis in the elderly presents significant diagnostic challenges, requiring a multifactorial approach that takes into account brain aging and the various medical conditions that can mimic or contribute to psychotic symptoms. Differential diagnosis is essential to ensure appropriate treatment, which, when properly targeted, can substantially improve patients’ quality of life. The impact of brain ageing on vulnerability to psychosis highlights the need for detailed clinical assessment and individualized therapeutic strategies for this population group.

Drivers of nest site selection and breeding success in an Alpine ground-nesting songbird

AbstractBirds breeding in high-Alpine habitats must select a suitable breeding site and achieve successful reproduction within a restricted time. During four breeding seasons, we monitored nest sites of the Northern Wheatear (Oenanthe oenanthe), a high-Alpine long-distance migrant. We investigated how ecological factors predicted the selection of a site for nesting within the home range, using conditional logistic regression. Birds preferred south-exposed productive pastures on gentle slopes, interspersed with non-vegetated ground and human-made rockpiles. The direct vicinity of conspecific nests was avoided, as were shrubby or north-exposed areas. We investigated if habitat also influenced breeding success. We analysed the impact of environmental factors on breeding success, which was primarily driven by predation. The probability of the brood fledging successfully decreased on north-exposed slopes or on areas with low coverage of non-vegetated ground. The vicinity of conspecific nests did not have a clear effect. Further, we describe how breeding success varied within and between years. Within years, replacement broods had a higher breeding success. The apparent absence of variation in breeding success between years and a delay of the breeding period in the year with late spring onset suggest a high level of tolerance with respect to inter-annual variation of meteorological conditions. Since the preferred habitat is still widely available in the Alps and given the negative population trends in Western Europe, the Alpine range might serve as a refuge for the Northern Wheatear, as long as low-intensity management and heterogenous habitats are maintained.

Early onset Colorectal Cancer and its association with its histological subtypes

Objective: There are different clinicopathological features between early and late onset colorectal cancer. We aimed to characterize the histological features of colorectal cancer (CRC) at different age groups in our institution. Methods: Total 232 patients with histologically proven colorectal cancer between ages 13-99 were included. This is retrospective study. Data collected from tumour registry Shifa International Hospital from January 1st 2018 to December 31st 2020. Pearson Chi square test was used for significance of categorical variables. P-values less than 0.05 were considered significant. Results: Mean age at diagnosis was 55.49+/-16.43 years. Out of total 232 patients 58.6% were male and 41.3% were females (p value= 0.16). 150 (64.9%) were aged > 50 years and 81 (35.1%) were age < or equal to 50 years (p value = 0.44). Most common histological subtype was adenocarcinoma that was found in 188 (81%) cases. One hundred fifty five (66.8%) patients had Grade-II tumor, 67(28.9%) with Grade-III and 10 (4.3%) with Grade-I tumor. Fifty eight (25%) patients presented with metastatic disease. A significantly higher percentage of patients with signet ring cell cancer presented with a high-grade tumor when compared with patients with adenocarcinoma and mucinous carcinoma (93.7% vs 21.8%, p-value- <0.001%; 93.7% vs 39.2%, p-value <0.001).A significantly higher percentage of patients with mucinous adenocarcinoma and signet ring cell carcinoma presented at age less than 50 as compared to those with adenocarcinoma (60.7%, 56.2% and 30.8% respectively; p-value <0.05). Conclusion: This study signifies that mucinous and signet ring cell type CRC present at an early age and with a higher proportion of patients with high tumour grade. Early diagnosis is key to help improve outcomes in these patients. doi: https://doi.org/10.12669/pjms.40.10.10143 How to cite this: Ibrar F, Atiq M, Shafqat F, Khan HM. Early onset Colorectal Cancer and its association with its histological subtypes. Pak J Med Sci. 2024;40(10):2395-2399. doi: https://doi.org/10.12669/pjms.40.10.10143 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Do preterm infants’ retinas like bovine colostrum? A randomized controlled trial

BackgroundBovine colostrum (BC) with liposomal delivery system (LDS) is a promising supplement to premature infant formula in absence of mother own milk. We propose that BC with LDS can target multiple etiological factors that threaten the developing retina, making premature infant less liable for retinopathy of prematurity (ROP). The aim of this study was to evaluate the effect of BC with LDS in the prevention of ROP.MethodsThis was a single center, randomized, controlled trial. Two hundred and eleven preterm infants of gestational age ≤ 32weeks were admitted to the NICU of Alexandria University Children Hospital, Egypt, and randomly allocated into either non-BC group (n = 105) or BC group (n = 106). Patients in BC group received 3.5 ml /kg/day of BC for 14 days. All patients were monitored for development of ROP, anemia, late onset sepsis (LOS), bronchopulmonary dysplasia (BPD), periventricular leukomalacia (PVL) and necrotizing enterocolitis (NEC), in addition to growth assessment. Multivariate binary logistic regression analysis was performed to determine factors predicting ROP development.ResultsCompared with the non-BC group, BC group was associated with a significantly lower incidence of ROP (5/100 vs. 16/100, respectively) with a p-value of 0.033. The administration of BC significantly decreased serum C- reactive protein (CRP) level and increased weight on day-14 of the study in comparison with the CRP level and birthweight at the beginning of study, with Cohen’s D= -0.184, D = -2.246, respectively. Patients with suspected sepsis were significantly less in BC than non-BC group, p = 0.004. Patients with BC had significantly higher hemoglobin level on day-14 than non-BC-group, with median (IQR) 12.2 (11.0–13.9) and 11.7 (10.5–12.9), respectively. BC intake is one of factors that decreased development of ROP in univariate analysis. Nevertheless, weight gain and birth weight were the most significant factors affecting ROP development in multivariate-regression model.ConclusionBC may reduce the incidence of ROP in preterm neonates aged ≤ 32 weeks. This might be due to keeping better Hb level and growth rate, as well as anti-inflammatory properties through its ability to decrease CRP level.Trial registrationThis work was registered on 06/13/2022 in clinicaltrial.gov with ID no.: NCT05438680 and URL:https://classic.clinicaltrials.gov/ct2/show/NCT05438680?term=NCT05438680&draw=2&rank=1.

Association of Age at Menarche with General and Abdominal Obesity in Young Women.

Background and Objectives: Age at menarche is related to various biological and socioeconomic factors in childhood. The aim of the study was to examine the association of age at menarche with general and abdominal obesity in young women. Materials and Methods: A transversal anthropometric survey was conducted with 102 females from 21 to 25 years of age. The surveyed traits included height, weight, waist circumference (WC) and hip circumference (HC). General obesity was assessed using the body mass index (BMI) and abdominal obesity by WC, waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR). A retrospective method was used for collecting age at menarche data. Results: The average age at menarche is 12.80 years. Early menarcheal age (<12 years) is detected in 25.5% of young females, while late onset of menarche (>14 years) is recorded for 20.6% of subjects. Early menarche age subjects exhibit significantly higher BMI, WC and WHtR in comparison with their late menarche age peers. There is a significant negative correlation between BMI, WC and WHtR values and menarcheal age. Late age at menarche is associated with higher probability of underweight status (BMI < 18.5 and/or WHtR < 0.4). Conclusions: Age at menarche has a negative correlation with general and abdominal obesity. Young women with early age at menarche show statistically higher values of BMI, WC and WHtR, while those with late menarcheal age show greater susceptibility to becoming underweight.

EXPRESS: Early Onset Colorectal Cancer, not just the Age: data from a large health organization.

Early onset colorectal cancer (EO-CRC) is increasing. We investigated the risk factors for ER-CRC compared to late onset CRC (LO-CRC). CRC patients between the years 1999 and 2021 were retrospectively evaluated. Data regarding demographics, comorbidities, malignancies, and mortality were collected. Data were retrieved using the MdClone platform from a large Health Maintenance Organization. The cohort was subdivided into EO-CRC (age ≤50 years) and LO-CRC (age ≥51 years) groups. 61,679 patients diagnosed with CRC were included in our analysis, 30,456 (49.4%) males, and 4,891 (7.9%) Arabs, with an average age at diagnosis of 70.1±13.1 years. 5561 (9%) patients were included in the EO-CRC group. Over the last decades, higher rates of EO-CRC were diagnosed compared to the previous decade, 9.8% vs 8.3%, p<0.001. A higher percentage of EO-CRC patients were females (52.8% vs 50.4%), had a family history of CRC (9.9% vs 5.5%), were Arabs (18.7% vs 6.9%), and were smokers (32.7% vs 30.2%) compared to LO-CRC patients. Significantly lower rates of comorbidities such as ischemic heart disease, diabetes mellitus, hypertension, obesity, and iron deficiency anemia were found among EO-CRC patients, with a lower all-cause mortality (27.7% vs 63.1%, p<0.001). 348 (6.3%) of the EO-CRC patients had another Lynch-related cancer until age 50 years compared to 45 (0.1%) at the LO-CRC. Young individuals with increased risk for CRC need special consideration and should be referred early for screening and endoscopic investigation, particularly those with a family history of CRC, smokers, and those of Arab ethnicity.

Strategic cultivar and sowing time selection for weed management and higher redgram productivity in semi-arid Indian regions

IntroductionRedgram (Cajanus cajan L. Mill sp.), a leguminous crop commonly grown in tropical and subtropical climates, is highly valued for its high protein content (21%), which contributes significantly to food and nutritional security. However, its production faces challenges primarily due to terminal dryness experienced during critical growth stages because of changing rainfall patterns. To overcome this, adaptive techniques become imperative as the productivity of this crop is intricately linked to environmental factors and the crop’s growth cycle.MethodsHence, the field experiment was conducted at the National Pulses Research Centre, Vamban, Pudukkottai, Tamil Nadu, in South India under rainfed condition, during the kharif (monsoon) seasons of 2017–18 and 2018–19. The primary objectives were to determine the optimal sowing time and identify suitable redgram cultivars, especially in the context of the late onset of the monsoon in Tamil Nadu, a common issue under changing climate conditions. The experiments tested six different sowing dates with three redgram cultivars.Results and discussionThe findings highlighted the substantial influence of different redgram cultivars and sowing times on the crop’s growth characteristics and yield. Among the six sowing dates tested, planting in later half of June (S6) resulted in notably higher plant height (201 cm), a greater number of pods per plant (287), a seed yield of 1,112 kg ha−1, and a benefit-cost ratio of 2.61 Notably, this sowing period (S6) demonstrated comparable performance with the treatment of redgram sowing in the latter part of September (S4). CO 6 (V1) is the most productive of the three redgram cultivars, with the highest mean pant height (200 cm), number of pods per plant (237), grain yield (1,017 kg ha−1), and benefit cost ratio (2.38). Extended phenological phases along with extra days to reach phenological stages could account for the increased yield in comparison to the other cultivars. Among the two short-duration cultivars, VBN (Rg) 3 (V3) had a significantly higher mean grain yield of 958 kg ha−1 with the benefit-cost ratio of 2.24. Even though CO 6 (V1) obtained a higher yield due to its long duration nature, it matured in 187 days whereas VBN (Rg) 3 (V3) matured within 129 days. Consequently, the short-duration redgram cultivars emerge as highly suitable choices for integrating into crop sequences, thereby augmenting farm cropping intensity.

Gitelman Syndrome in a 37-Years Old Woman with Urinary Tract Syndrome and History of Caesarean Section: A Case Report

Gitelman Syndrome (GS) is a rare genetic disorder often underdiagnosed due to its non-specific symptoms that can appear from neonatal stages to adulthood. It is more frequently observed in Asians, with a prevalence of approximately 1 in 40,000 people. Accurate diagnosis requires a comprehensive clinical interview and laboratory examinations. This report presents the case of a 37-year-old woman with GS who also experienced a urinary tract infection and had a history of cesarean section. Upon admission, she reported feeling fatigued and weak in all extremities. She had undergone a cesarean section a month prior due to pre-eclampsia. Initial laboratory tests revealed hypokalaemia, hyponatremia, and hypochloraemia. Further evaluation during hospitalization detected a urinary tract infection, hypocalciuria, and hypomagnesemia. The patient also suffered from carpopedal spasms and muscle cramps. Treatment included magnesium sulfate, calcium gluconate, potassium chloride, and sodium chloride infusions to restore electrolyte balance. The patient was discharged after six days, with a diagnosis of Gitelman Syndrome, which was unusual given her late onset of symptoms, as most cases are identified in childhood. The clinical presentation was largely driven by the patient’s electrolyte imbalances, especially hypokalaemia and hypomagnesemia, with hypomagnesemia further contributing to hypocalcemia and vitamin D deficiency. The patient’s symptoms improved after appropriate electrolyte supplementation. This case emphasizes the importance of a detailed clinical history and laboratory assessments in diagnosing GS, along with timely correction of electrolyte disturbances to improve the patient’s condition and prevent complications.

Racial/ethnic differences in the association of incident stroke with late onset epilepsy: The Northern Manhattan Study.

Little is known about the incidence of late onset epilepsy (LOE) across different racial/ethnic groups in the USA, particularly in the Hispanic population. Stroke, a strong predictor of LOE, is more common in non-Hispanic Blacks (NHBs) and Hispanics than in non-Hispanic Whites (NHWs). We assessed the incidence of LOE across racial/ethnic groups and examined whether the associations of stroke with LOE risk differ by race/ethnicity. The Northern Manhattan Study is a population-based longitudinal study of older adults enrolled between 1993 and 2001. Participants free of history of stroke or epilepsy at baseline (n = 3419) were followed prospectively for incidence of LOE. We estimated LOE incidence per 1000 person-years in each racial/ethnic group. We used Cox proportional hazards regression to assess the association of race/ethnicity with LOE and multiplicative interactions of race/ethnicity with incident stroke in relation to LOE, adjusting for demographics and comorbid diagnoses. During 51 176 person-years of follow-up, 183 individuals developed LOE. Incidence of LOE was significantly higher in NHBs (6.2 per 1000 person-years) than in NHWs (3.3 per 1000 person-years, p = .004). There was no significant difference in LOE incidence between NHWs (3.3 per 1000 person-years) and Hispanics (2.6 per 1000 person-years, p = .875). However, following incident stroke, the risk of LOE differed across racial/ethnic groups. Incident stroke was associated with 2.55 times the risk of LOE among NHWs (95% confidence interval [CI] = .88-7.35), 8.53 times the risk of LOE among Hispanics (95% CI = 5.36-13.57, p = .04 for stronger association than that in NHWs), and 6.46 times the risk of LOE among NHBs (95% CI = 3.79-11.01, p = .12 for stronger association than that in NHWs). We found a stronger association of incident stroke with LOE risk in Hispanics and NHBs than in NHWs, offering some insight into the racial/ethnic disparities of LOE incidence.

Comparison of Short vs. Extended Antibiotic Durations for Patients in the Neonatal Intensive Care Unit with Late Onset, Culture-negative Sepsis

Abstract Background Culture-proven late-onset sepsis in neonates and preterm infants, defined as symptom onset after 3-7 days of life, is a common cause of morbidity and mortality. Some patients are treated with antibiotics for sepsis despite lack of positive cultures after 48 hours of incubation, potentially due to the non-traditional signs of sepsis. Controversy remains over optimal treatment durations of culture-negative sepsis with durations reported as 2 to 7 days, and rarely longer than 7 days. The primary outcome of this study is to compare lack of symptom resolution at 7 days in patients with negative cultures treated with antibiotics for either ≤72 hours or &amp;gt;72 hours. Methods This was a single-center, retrospective, cohort study with Institutional Review Board approval at a 60 bed, level 4, surgical referral neonatal intensive care unit from January 1, 2020, to December 31, 2021. Patients were included for screening if they were ≥7 days of age, ≤ 44 weeks postmenstrual age, and received more than 1 day of antibiotics for possible late-onset, culture-negative sepsis. Patients were then excluded if they had positive culture results from any site, diagnosis of pneumonia, were being treated for suspicion of necrotizing enterocolitis, received antibiotics prior to obtaining cultures, or had continued treatment of prior infection. Patients were divided into two groups based on antibiotic duration: ≤72 hours or &amp;gt;72 hours. Presenting symptoms and symptom resolution at 72 hours and 7 days were assessed. Chi-squared or Fisher’s exact tests were used for categorical comparisons. Results Of the 909 patients screened, 68 were included: 42 in the ≤72 hours group and 26 in the &amp;gt;72 hours group. The most prevalent symptoms prompting antibiotic initiation were elevated CRP (64.7%) and bradycardia/oxygen desaturations (78%), with elevated CRP being the initiating symptom more frequently in the &amp;gt;72-hour group (92% vs 48%, p&amp;lt;0.001). If patients had 2 or more symptoms, they were more likely to receive &amp;gt;72 hours of antibiotics (85% vs 62%, p=0.034). At 7 days, 28 (41%) patients had complete symptom resolution. Antibiotic duration ≤72 hours was not associated with symptom resolution at 7 days (50% symptom resolution in the ≤72-hour group vs 27% in the &amp;gt; 72-hour group, p=0.06). Lack of symptom resolution at 72 hours of antibiotics was associated with lack of resolution at 7 days (p&amp;lt;0.001). Among patients without symptom resolution at 7 days, 65% of patients had a persistently elevated CRP and 68% of patients continued to have bradycardia/oxygen desaturations. Conclusion In neonates and preterm infants with negative cultures but possible signs of sepsis, antibiotic duration does not impact 7-day symptom resolution. Results indicate that if the initiating symptom is not resolved at 72 hours despite negative cultures, it is unlikely to be resolved with additional days of antibiotics. This is likely due to the multifactorial potentially non-infectious etiology of initiating symptoms in these patients. It is appropriate to discontinue antibiotics if cultures are negative after 48 hours of incubation in this population.

The Type VII Secretion System (T7SSb) contributes to interbacterial competition in a murine model of Group BStreptococcus gastrointestinal colonization

Abstract Background Late-onset (LO) disease caused by Group B Streptococcus (GBS) infection is a significant source of morbidity and mortality in neonates. It is believed that gastrointestinal (GI) colonization with GBS plays an important role in the progression to LO disease, although the host-microbial interactions that facilitate GBS GI colonization are poorly understood. The Type VII secretion system (T7SSb) has been identified in several gram-positive bacteria, and its function depends on a membrane-bound ATPase (EssC) which drives secretion of virulence factors. In GBS, the T7SSb has been shown to contribute to vaginal colonization and brain cytotoxicity. We aimed to identify the role of the T7SSb in GBS GI colonization using a murine model and hypothesize that the T7SSb is necessary for sustained GBS GI colonization. Methods Two bacterial strains were used, a wild-type (WT) GBS of A909 background (serotype Ia) and an isogenic T7SSb mutant GBS strain (essC::Himar1, transposon inserted). Monocolonization and co-cocolonization experiments were performed by orally inoculating preweaning C57BL/6J mice (12-14 days of life) with one or both strains, respectively. Euthanasia was performed, rectal swabs collected, and the GI tract harvested at day 7 post infection. For co-colonization experiments, competitive indices were calculated at day 7 post infection to determine the contribution of T7SSb to GBS GI colonization. For monocolonization experiments, colonization status and bacterial burden at day 7 post infection were measured. Results In cocolonization, WT GBS A909 outcompeted the essC::Himar1 mutant at 7-days post infection with a geometric mean competitive index of 8.8, 95% CI [0.2, 350.1] by rectal swab; 35.7, 95% CI [19.2, 66.3] in the small intestine; 87.6, 95% CI [18.9, 407] in the cecum; and 91.7, 95% CI [33.4, 252] in the colon (Figure 1a). In monocolonization, we noted similar rates of colonization (p=NS, Fisher’s exact test) (Figure 1b) and no difference in bacterial burden (p=NS, 2-way ANOVA test) (Figure 1c) across the GI tract at 7 days post infection. Conclusion Our results suggest that T7SSb plays an important role in GBS bacterial competition in the GI tract but is likely not an essential factor for GBS GI colonization. Further exploration of the role of the T7SSb in interbacterial competition may yield relevant information regarding GI colonization dynamics. Figure 1. Establishing the role of T7SSb in a murine model of GI colonization. (a) Wild type (WT) A909 confers an advantage over an isogenic T7SSb mutant (essC::Himar1) strain in a cocolonization model. Data points represent geometric mean competition indices and error bars represent 95% confidence interval. (b) Colonization status by WT A909 and essC::Himar1 mutant in the GI tract 7-days post infection in monocolonization experiments (p-values represent two-sided Fisher’s exact test). (c) Bacterial burden of monocolonization by WT A909 and essC::Himar1 mutant in the GI tract 7-days post infection (p-values represent 2-way ANOVA test).

Psychological Impact of Acne and Post Inflammatory Hyperpigmentation Among Sudanese Women

&amp;lt;i&amp;gt;Introduction: &amp;lt;/i&amp;gt;Acne vulgaris is a chronic inflammatory disorder of the skin which often causes a negative impact on a woman&amp;apos;s psychological state and quality of life. This study seeks to provide basic data and information about the psychological impact of acne on Sudanese women. &amp;lt;i&amp;gt;Methodology: &amp;lt;/i&amp;gt;A cross-sectional questionnaire-based study was conducted during the period from June 2022 to January 2023. A total of 400 females aged 15 years and above were included in this study. These are Sudanese women who had suffered from acne in their lives, and who responded to the online study questionnaire. Cardiff Acne Disability Index (CADI) was used to assess the psychological effect of acne.&amp;lt;i&amp;gt; Results: &amp;lt;/i&amp;gt;Seventy one percent of respondents had active acne. Acne scars were observed in (74.8%) of participants, while post-acne hyperpigmentation was observed in (71.3%). Facial acne was the most common, as it was observed in (75.8%) of the respondents. The mean age at acne onset was 15.66 years and ranged between 10 and 36 years. Mild and moderate acne were the most common types, accounting for (37.0%) and (41.5%) of cases, respectively. Acne was found to affect the psychological state of the vast majority of the respondents (89%). Cosmetics or makeup were used by (42.3%) of the respondents to conceal acne and scars. Late onset of acne treatment was reported in (42%) of the cases. Most respondents (72.5%) visited doctors to treat acne. The mean Cardiff Acne Disability Index (CADI) score was 4.55, which reflects mild effects of acne on the quality of life of most of the respondents. The adverse psychological impact was found to be significantly associated with increased acne severity, scarring, and hyperpigmentation as well as with university educated respondents. &amp;lt;i&amp;gt;Conclusion: &amp;lt;/i&amp;gt;It was found that acne has mild effects on the quality of life of Sudanese women. Late onset of acne treatment resulted in widespread scarring and post-inflammatory hyperpigmentation in most participants, which was associated with the psychological impact of acne. There is an urgent need to encourage early treatment of acne to reduce the physical sequalae of acne to reduce the psychosocial consequences associated with the disease and the risk of scarring and hyperpigmentation on Sudanese women. Sudanese health authorities and Sudanese doctors can address this issue through education and awareness programs.

Apolipoprotein B gene expression and regulation in relation to Alzheimer’s disease pathophysiology

Apolipoprotein B (APOB), a receptor-binding protein present in cholesterol-rich lipoproteins, has been implicated in Alzheimer's disease (AD). High levels of APOB-containing low-density lipoproteins (LDL) are linked to the pathogenesis of both early-onset familial and late onset sporadic AD. Rare coding mutations in the APOB gene are associated with familial AD, suggesting a role for APOB-bound lipoproteins in the central nervous system.This research explores APOB gene regulation across the AD spectrum using four cohorts: BRAINEAC (elderly control brains), DBCBB (controls, AD brains), ROSMAP (controls, MCI, AD brains), and ADNI (control, MCI, AD clinical subjects). APOB protein levels, measured via mass spectrometry and ELISA, positively correlated with AD pathology indices and cognition, while APOB mRNA levels showed negative correlations. Brain APOB protein levels also correlated with cortical Aβ levels.A common coding variant in the APOB gene locus affected its expression but didn't impact AD risk or brain cholesterol concentrations, except for 24-S-hydroxycholesterol. Polymorphisms in the CYP27A1 gene, notably rs4674344, were associated with APOB protein levels. A negative correlation was observed between brain APOB gene expression and AD biomarker levels. CSF APOB correlated with Tau pathology in presymptomatic subjects, while cortical APOB was strongly associated with cortical Aβ deposition in late-stage AD.The study discusses the potential link between blood-brain barrier dysfunction and AD symptoms in relation to APOB neurobiology. Overall, APOB's involvement in lipoprotein metabolism appears to influence AD pathology across different stages of the disease.

Functional outcome and histologic analysis of late onset total type brachial plexus injury treated with intercostal nerve transfer to median nerve with local umbilical cord-derived mesenchymal stem cells or secretome injection: a double-blinded, randomized control study.

Intercostal nerve transfer is a surgical technique used to restore function in patients with total brachial plexus injury. Stem cell and secretome therapy has been explored as a potential treatment for brachial plexus injuries. This study aimed to compare the functional and histologic outcome of intercostal nerve transfer to median nerve with local stem cells or secretome injection in total type brachial plexus injuries. This was a double-blinded, randomized controlled study (RCT). We included patients with neglected total type brachial plexus injury (BPI) who underwent nerve transfer and local injection of either umbilical cord-derivedmesenchymal stem cells (UC-MSC) or secretome into median nerve-flexor digitorum superficialis (FDS) neuromuscular junction (NMJ). We measured preoperative and 8-month postoperative FDS muscle strength, SF-36, DASH score, and histologic assessment. We then analyzed the difference outcome between those two groups. A total of 15 patients were included in this study. Our study found that after nerve transfer and implantation with either UC-MSC or secretome, significant postoperative improvements were observed in physical functioning, role limitations, energy/fatigue, emotional well-being, social functioning, pain, general health, and DASH scores, particularly in the overall cohort and the secretome group. When we compared the mean difference of clinical outcome from preoperative to postoperative between UC-MSC and secretome groups, the UC-MSC group showed better improvement of health change in SF-36 subgroup compared to secretome group. From the analysis, there was no significant difference in the histologic outcomes (inflammation, regeneration, and fibrosis) in overall cohort between preoperative and postoperative cohort. There was also no significant difference in mean change of the histologic outcomes (inflammation, regeneration, and fibrosis) preoperative and postoperatively between UC-MSC and secretome groups. Implantation of either UC-MSC or secretome along with nerve transfer may provide clinical improvement, while to achieve histologic improvement, further conditioning should be performed.

The role of therapeutic plasma exchange using membrane plasma separation in the late onset myasthenic crisis: a case report

Myasthenia gravis (MG) is an autoimmune disease, in which antibodies bind to receptors in the neuromuscular junction (NMJ), causing muscle weakness. This disease is relatively challenging to diagnose due to its late onset and comorbidities. Several treatment options include therapeutic plasma exchange (TPE) with membrane plasma separation, that aims to remove large molecular-weight toxins such as pathogenic antibodies and lipoproteins. A 61-year-old male patient was admitted to the ICU post-sternotomy due to mediastinal tumor resection. Extubation failed, so we decided to undergo a tracheostomy. The lung pathology result showed lymphocyte-predominant thymoma, and along with symptoms of chest weakness and ptosis, the patient was suspected for MG. Electromyography results confirmed the occurrence of functional lesions in post-synaptic NMJ consistent with MG. We assessed patient with myasthenic crisis (MC), then gave pyridostigmine 60 mg 6x/day, and planned for TPE using membrane plasma separation. Plasma exchange was done by 1.5 of blood volume. The patient developed sepsis pneumonia and was administered levofloxacin based on his culture results. Patient still had weakness. We re-evaluated the drugs that might have exacerbated MG. Aztreonam in combination with co-trimoxazole was administered to combat Stenotrophomonas maltophilia pneumonia. The patient was eventually weaned from the ventilator and gradually recovered. Keywords: Membrane Plasma Separation; Myasthenia Gravis Crisis; Therapeutic Plasma Exchange; TPE Citation: Kurnia D, Manggala SK, Irawany V. The role of therapeutic plasma exchange using membrane plasma separation in the late onset myasthenia gravis crisis: a case report. Anaesth. pain intensive care 2024;28(5):969−973; DOI: 10.35975/apic.v28i5.2557 Received: July 17, 2024; Reviewed: August 01, 2024; Accepted: August 01, 2024