Search Results (50)

Background: Histoplasma capsulatum is an environmentally acquired dimorphic fungus. Infection results in histoplasmosis, a clinical syndrome often underdiagnosed and that may progress to life-threatening disseminated infection not only in immunocompromised individuals but also, following high-level exposure, in immunocompetent hosts. Epidemiological data from Caribbean regions, and particularly from Guadeloupe, remain limited. Methods: We performed a retrospective cohort study of all microbiologically confirmed histoplasmosis cases managed at the University Hospital of Guadeloupe between January 2014 and October 2024. Demographic, clinical, diagnostic, therapeutic, and outcome data were retrieved from medical records and analyzed using descriptive statistics. Results: Forty-two patients met the inclusion criteria, corresponding to an estimated annual incidence rate of 1 per 100,000 inhabitants. The median age was 52 years, and the male-to-female ratio was 4:1. An underlying immunocompromising condition was present in 85% of cases, most commonly HIV infection (48%). Common clinical features included weight loss (97%), fever (89%), and pulmonary manifestations (81%). The mean time to diagnosis from hospital admission was 3.5 ± 10.3 days. Direct microscopy was positive in 67% of cases, and culture was positive in 88% of cases. Intravenous liposomal amphotericin B constituted the initial therapy in 71% of patients. Overall, the in-hospital mortality was 29%, rising to 40% among HIV-positive individuals. The 30-day survival rate was 71%. Conclusions: Histoplasmosis in Guadeloupe is under-recognized and associated with appreciable morbidity and mortality in both immunocompromised and immunocompetent patients. The wider availability of rapid diagnostics and heightened clinical vigilance are essential to shorten diagnostic delays and improve outcomes in this Caribbean population. Full article

Background/Objectives: The corneal epithelium plays a vital role in maintaining corneal transparency and ocular surface integrity. Chronic topical use of antiglaucoma medications may induce epithelial changes, especially with the concurrent use of multiple agents. This study aimed to evaluate the association between the number and class of antiglaucoma medications and central corneal epithelial thickness (CET), measured using a spectral-domain optical coherence tomography (SD-OCT) device. Methods: This cross-sectional study included 456 eyes from 242 adults (median age 72 years), grouped by the number of antiglaucoma agents used (0–4 medications). All pharmacologically treated participants had received the same regimen for ≥6 months. CET was measured using SD-OCT (SOLIX, Optovue). Generalized estimating equations (GEEs) accounted for inter-eye correlation. Two models were constructed: one evaluating specific medication effects and another assessing CET reduction per additional drug used. Age and sex were included as covariates. Results: CET progressively decreased with the number of medications, ranging from 53 µm in controls to 48 µm with quadruple therapy. Multivariable GEE analysis confirmed a cumulative thinning effect, with each additional medication associated with further CET reduction (β = −2.83 to −9.17 µm, p < 0.001). Latanoprost exerted the most pronounced single-drug effect (β = −3.01 µm, p < 0.001). Age was a modest negative predictor, while sex showed no significant effect. Conclusions: The cumulative number and specific class of antiglaucoma medications have a significant impact on corneal epithelial thickness. These results emphasize the need for vigilant ocular surface evaluation in patients on multi-drug regimens and propose CET as a surrogate marker for the burden of topical therapy. Full article

Clostridioides difficile infection (CDI) appears mainly as nosocomial antibiotic-associated diarrhea, and community-acquired infection is increasingly being recognized. The threshold of asymptomatic colonization and the clinical manifestation of CDI need further elucidation. Community-acquired CDI (CA-CDI) should be considered when the disease commences within 48 h of admission to hospital or more than 12 weeks after discharge. Although CDI is not established as a food-borne or zoonotic disease, some data support that direction. The spores’ ability to survive standard cooking procedures and on abiotic surfaces, the formation of biofilms, and their survival within biofilms of other bacteria render even a low number of spores capable of food contamination and spread. Adequate enumeration methods for detecting a low number of spores in food have not been developed. Primary care physicians should take CA-CDI into consideration in the differential diagnosis of diarrhea, as there is a thin line between colonization and infection. In patients diagnosed with inflammatory bowel disease and other comorbidities, C. difficile can be the cause of recurrent disease and should be included in the estimation of diarrhea and worsening colitis symptoms. In the community setting, it is difficult to distinguish asymptomatic carriage from true infection. For asymptomatic carriage, antibiotic therapy is not suggested but contact isolation and hand-washing practices are required. Primary healthcare providers should be vigilant and implement infection control policies for the prevention of C. difficile spread. Full article

Background/Objectives: Post-market surveillance of COVID-19 vaccines is vital. This study analyzed EudraVigilance data (Jan 2021–Dec 2023) to detect potential safety signals linking COVID-19 vaccines and specific neurological adverse events (aseptic meningitis, Guillain–Barré syndrome, polyradiculoneuropathies, multiple sclerosis, transverse myelitis, neuromyelitis optica). It also explored the impact of non-healthcare professional reports on disproportionality analysis. Methods: EudraVigilance reports were analyzed to quantify neurological events for 5 COVID-19 vaccines and 47 comparators. Disproportionality was assessed using the Proportional Reporting Ratio (PRR). Spearman’s correlation (SCC) was used to examine the impact of non-healthcare professional reports on PRR. Results: An analysis of 4,159,820 COVID-19 vaccine and 114,025 comparator reports showed a reporting decline over time. A higher proportion of adverse drug event reports were submitted by non-healthcare professionals for COVID-19 vaccines compared to control vaccines, a trend observed consistently across 2021 (57.3% vs. 33%, p < 0.001), 2022 (59.4% vs. 36.5%, p = 0.001), and 2023 (42% vs. 24.36%, p = 0.006). In 2023, significant signals (PRR ≥ 2) were found between Jcovden© and polyradiculoneuropathy (PRR 5.4, IC 95% 3.98–7.32), multiple sclerosis (PRR 2.72, IC 95% (1.08–6.87), transverse myelitis (PRR 4.68, IC 95% 1.02–21.35) and neuromyelitis optica (PRR 7.79, IC 95% 3.5–17.37). In addition, both Spikevax© and Comirnaty© showed significant signals with multiple sclerosis (PRR 2.50, IC 95% 1.70–3.68, and PRR 2.33, IC 95% 1.68–3.24) and transverse myelitis (PRR 3.50, IC 95% 1.66–7.50 and PRR 3.58, IC 95% 1.85–6.93). A significant negative correlation between the proportion of reports from non-healthcare professionals and the case/no-case ratio was found (SCC = −0.4683, p = 0.009). Conclusions: While some significant signals emerged in 2023, the combined three-year data showed no vaccine exceeding the PRR threshold of 2. High-quality data and bias mitigation strategies are crucial for accurate PRR estimation in pharmacovigilance and public health. Full article

Background/Objectives: Although kidney transplant recipients (KTRs) who are immune-compromised have been shown to be at high risk of adverse acute COVID-19 outcomes (i.e., mortality and critical illness), the long-term outcomes of KTRs with a history of SARS-CoV-2 infection are unknown. We aimed to compare long-term outcomes of KTRs with and without exposure to SARS-CoV-2. Methods: This study retrospectively evaluated 1815 KTRs in the Montefiore Health System from 4 January 2001 to 31 January 2024. The final cohorts consisted of KTRs who survived COVID-19 (n = 510) and matched KTRs without COVID-19 (n = 510, controls). Outcomes were defined as all-cause mortality and changes in estimated glomerular filtration rate (eGFR) and urine protein to creatinine ratio (UPCR) from 30 days up to four years post index date. Kaplan–Meier survival analysis and Cox proportional modeling were performed for mortality. Generalized estimating equations were used to analyze changes in eGFR and UPCR across time. Results: There was no significant group difference in long-term all-cause mortality (adjusted hazard ratio = 0.66, [0.43, 1.01] p = 0.057). eGFR in controls and COVID-19 patients before infection similarly decreased −0.98 units/year [−1.50, −0.46]. By contrast, eGFR declined at a significantly greater rate (−1.80 units/year [−2.45, −1.15]) in KTRs after COVID-19 compared to KTRs without COVID-19. This association was only seen among male and not female KTRs. COVID-19 status was not significantly associated with rate of change in UPCR or acute kidney rejection rate. Conclusions: SARS-CoV-2 infection was associated with an accelerated decline in eGFR up to four years post infection, suggesting potential long-term implications for graft health. These findings underscore the importance of vigilant monitoring and management of kidney function post SARS-CoV-2 infection in this vulnerable population. Full article

The aim of this investigation was to measure the natural nocturnal plasma melatonin concentration in gestating and fresh ewes. Studies in humans showed that maternal melatonin had a significant increase as pregnancy progressed and then decreased after birth. Two studies conducted in sheep so far, considering the entire gestation, have led to conflicting results. The breed of 16 pregnant ewes selected for the research was the Tsigai. Blood samples were taken into EDTA vacutainers predetermined times a night at different stages of their gestation. The RIA method was used to determine the melatonin concentrations. For estimation of its variations during gestation, population genetic statistics was applied. It was found that the average plasma melatonin concentration of 134 pg mL⁻¹ is characteristic for the investigated period, and that it rises between the autumnal equinox and the winter solstice. Secondly, it was revealed that the average melatonin concentration adjusted for midnight is 162.4 pg mL⁻¹, and its moderate variation is characteristic for the night. The investigation showed that there is no connection between the plasma melatonin concentration of the ewes and their gestational age in the Tsigai breed in Middle Europe. Our result is consistent with the results of single studies in sheep and donkey, in contrast to human observations. With regard to the nocturnal plasma melatonin, the concentration is reduced at the same level (30 pg mL⁻¹) in ewes and lambs during the early postpartum period without nightly fluctuation. The expelled placenta, the constant vigilance between the mother and her lamb, and the opposition between melatonin and prolactin may provide a plausible explanation for this. Full article

Background/Objectives: Spinal cord injury (SCI) causes profound autonomic and endocrine dysfunctions, giving rise to adrenal insufficiency (AI), which is marked by a reduction in steroid hormone production. Left unaddressed, SCI-related AI (SCI-AI) can lead to life-threatening consequences such as severe hypotension and shock (i.e., adrenal crisis). However, symptoms are often non-specific, making AI challenging to distinguish from similar or overlapping cardiovascular conditions (e.g., orthostatic hypotension). Additionally, the etiology of SCI-AI remains unknown. This review aimed to synthesize the current literature reporting the prevalence, symptomology, and management of SCI-AI. Methods: A systematic search was performed to identify studies reporting AI following the cessation of glucocorticoid treatments in individuals with traumatic SCI. A random-effects meta-analysis was conducted to investigate the overall prevalence of SCI-AI. Results: Thirteen studies involving 545 individuals with traumatic SCI, most with cervical level injuries (n = 256), met the review criteria. A total of 4 studies were included in the meta-analysis. Primary analysis results indicated an SCI-AI pooled prevalence of 24.3% (event rate [ER] = 0.243, 95% confidence interval [CI] = 0.073–0.565, n = 4). Additional sensitivity analyses showed a pooled prevalence of 46.3% (ER = 0.463, 95%CI = 0.348–0.582, n = 2) and 10.8% (ER = 0.108, 95%CI = 0.025–0.368, n = 2) for case–control and retrospective cohort studies, respectively. High-dose glucocorticoid administration after SCI as well as the injury itself appear to contribute to the development of AI. Conclusions: The estimated prevalence of AI in people with traumatic SCI was high (24%). Prevalence was also greater among individuals with cervical SCI than those with lower-level lesions. Clinicians should be vigilant in recognizing the symptomatology and onset of SCI-AI. Further research elucidating its underlying pathophysiology is needed to optimize glucocorticoid administration for remediating AI in this vulnerable population. Full article

Patients with mild cognitive impairment due to Alzheimer’s disease (ADMCI) typically show abnormally high delta (<4 Hz) and low alpha (8–12 Hz) rhythms measured from resting-state eyes-closed electroencephalographic (rsEEG) activity. Here, we hypothesized that the abnormalities in rsEEG activity may be greater in ADMCI patients than in those with MCI not due to AD (noADMCI). Furthermore, they may be associated with the diagnostic cerebrospinal fluid (CSF) amyloid–tau biomarkers in ADMCI patients. An international database provided clinical–demographic–rsEEG datasets for cognitively unimpaired older (Healthy; N = 45), ADMCI (N = 70), and noADMCI (N = 45) participants. The rsEEG rhythms spanned individual delta, theta, and alpha frequency bands. The eLORETA freeware estimated cortical rsEEG sources. Posterior rsEEG alpha source activities were reduced in the ADMCI group compared not only to the Healthy group but also to the noADMCI group (p < 0.001). Negative associations between the CSF phospho-tau and total tau levels and posterior rsEEG alpha source activities were observed in the ADMCI group (p < 0.001), whereas those with CSF amyloid beta 42 levels were marginal. These results suggest that neurophysiological brain neural oscillatory synchronization mechanisms regulating cortical arousal and vigilance through rsEEG alpha rhythms are mainly affected by brain tauopathy in ADMCI patients. Full article

(1) Car tyre microplastic particles (TMPs) significantly contribute to global microplastic pollution, with an estimated annual production of 6 million tonnes. However, the impact of TMPs, particularly tyre and road wear particles (TRWPs), resulting from tyre abrasion on the road on terrestrial organisms, is poorly understood. This study investigated the effects of TMPs and TRWPs on the growth, immune response, behaviour, and cognition of the woodlouse Armadillidium pallasii over 30 days; (2) TMPs and TRWPs were mixed together in the first experiment and provided at different concentrations of 1.25%, 2.5%, 5%, and 10% (w/w), and with soil at 5% and 10% (w/w) concentrations in the second experiment. (3) No differences in survival or immune responses were observed in both experiments. However, isopods exposed to TRWPs showed significant weight gain at lower concentrations but no gain at higher levels. Behavioural tests revealed increased vigilance in TRWP-exposed animals. Micro-FTIR analysis showed that the number of TMPs and TRWPs in the isopods correlated with soil concentrations, and particle size decreased during the experiment. (4) The study highlights the physiological and behavioural effects of TRWPs and the role of detritivorous species in the biofragmentation of TMPs and TRWPs, contributing to the biogeochemical plastic cycle. Full article

Background: Sarcoidosis is a multisystem granulomatous disorder with a variable clinical course and complications. The relationship between sarcoidosis and malignancies remains unclear, including specific malignancy associations with sarcoidosis and whether the association is short-term, long-term, or a result of misdiagnoses or coincidence. This study investigated the association between sarcoidosis and malignancy by analyzing the varying intervals between the diagnoses of these two conditions to clarify their inter-relationship. Methods: This retrospective cohort study included almost 24,000 sarcoidosis patients and matched controls at a 1:5 ratio in patients diagnosed between 2000 and 2015 in Israel. Patients had a median age of 57 years. Malignancy rates were compared across several timeframes: overall, within one year before or after sarcoidosis diagnosis and more than one year. Logistic regression models were employed to estimate odds ratios for the association between sarcoidosis and malignancy, adjusting for sociodemographic and clinical variables. Results: Sarcoidosis patients had a significantly higher prevalence of malignancies (19.5%) compared to controls (13.6%) (p < 0.001). The association remained significant for both hematologic malignancies (OR: 2.94, 95% CI: 2.41–3.57) and solid malignancies (OR: 1.41, 95% CI: 1.27–1.55). The strongest association was observed with lymphoma, particularly within the first year of sarcoidosis diagnosis (OR: 14.88, 95% CI: 8.83–25.1). Elevated odds for malignancies persisted both within one year and beyond, including sarcoma and soft tissue cancers and genitourinary malignancies. Conclusions: Our study confirms a significant association between sarcoidosis and both hematologic and solid malignancies in both the short and long term across various timeframes. These findings emphasize the need for increased clinical vigilance in sarcoidosis patients and highlight the importance of further research into the shared genetic and environmental mechanisms that may underlie this relationship. Full article

Vaginal cuff dehiscence can be a rare complication of total hysterectomy, with an estimated prevalence of 0.032% to 1.25% and a high mortality rate of 6 to 10%. Dehiscence is also reported in cases following total laparoscopic hysterectomy, with a prevalence of 0.87%. This case report details the emergency management of a 59-year-old female who complained of abdominal and pelvic pain and the feeling of a foreign body in her vagina. The patient reported a history of laparoscopic total hysterectomy 6 months prior to presenting at the Emergency Department. A clinical examination revealed small bowel loops protruding through the vagina. The patient underwent exploratory laparotomy through a Pfannenstiel incision, and the terminal ileum was found prolapsing through the vaginal cuff. The bowel loops were identified as viable and the vagina was sutured. The patient had an unremarked post operative course. This case report showcases that in patients with transvaginal evisceration, immediate surgical management is crucial in order to avoid serious life threatening complications, and both surgeons and gynecologists should remain vigilant regarding this pathology. Full article

Background: Total hip arthroplasty (THA) is a well-established and effective treatment for advanced osteoarthritis (OA) of the hip joint. While commonly performed in older patients, THA is increasingly used in younger individuals, especially in cases of secondary coxarthrosis. Technological advances have led to the development of specialized implants, which allow surgeons to address severe post-inflammatory or dysplastic deformities. Younger patients undergoing THA, often in their 20s or 30s, present higher functional expectations. Despite limited long-term studies, research indicates a higher rate of revision surgeries in this age group compared to older populations, making these procedures a unique challenge. Methods: This retrospective study analyzed 5263 primary total hip arthroplasties (THAs) performed at our center between May 1985 and December 2016. After excluding cemented and hybrid implants, as well as patients lost to follow-up or with other etiologies, 101 uncemented THA procedures in 92 patients aged 30 years or younger were included. The majority (64.4%) were due to dysplastic coxarthrosis (DDH), while avascular necrosis (26.7%) and juvenile rheumatoid arthritis (8.9%) accounted for the rest. The average patient age was 25.6 years, with a mean follow-up period of over 24 years. Surgical technique involved the anterolateral approach, with implants placed in the true acetabular region. Implants included Munich/Plasmacup, Mittelmeier, and P-M designs. Implant survival was estimated using the Kaplan–Meier estimator to determine the probability of implant longevity over the follow-up period. Outcomes were assessed using Merle d’Aubigné and Postel scores, modified by Charnley, alongside radiographic evaluations based on the Crowe, De Lee, and Gruen classifications. Results: Preoperatively radiological assessment of all hips was classified as grade IV according to the Kellgren–Lawrence scale. Over an average follow-up of 24 years, final outcomes using the modified Merle d’Aubigné and Postel (MAP) classification were excellent in 24%, good in 37%, satisfactory in 8%, and poor in 32% of cases. Results compared between DDH group and control group indicate significantly more poor results for the DDH group compared to the control group (p-value < 0.05). All poor outcomes were associated with prosthesis loosening, primarily involving P-M and Mittelmeier acetabular components. Complications included intraoperative fractures in five cases, peripheral nerve dysfunction in six cases, and heterotopic ossification in eight cases. Postoperative pain scores on the VAS scale improved from 6.8 to 1.7. The Kaplan–Meier estimator indicated 10-year survival rates of 85.2% for the entire prosthesis, with 69.8% survival at 15 years and 54.5% at 20 years. For each period the bio-functionality according to Kaplan–Meier estimator was in favor of the control group. Conclusions: Cementless THA in patients aged 30 or younger has demonstrated itself to be an efficacious treatment for hip osteoarthritis, yielding favorable bio-functional outcomes in both short- and long-term follow-up. Nevertheless, THA performed in the context of developmental dysplasia of the hip (DDH) carries a significantly elevated risk of postoperative complications, most notably aseptic loosening, which critically undermines implant survival rates. Given the young demographic and the anticipated prolonged functional lifespan of the prosthesis, there is an increased propensity for loosening over time, necessitating vigilant and sustained postoperative surveillance. Full article

A 2018 report from the Water Quality for Human Consumption Vigilance Information System (SISÁGUA, Brazil) showed the presence of 27 pesticides in Brazilian drinking water, of which 11 have carcinogenic potential. We assessed the data for 27 municipalities in Paraná state southwest, a rural landscape with high cancer rates. We selected data from the carcinogenic potential of 11 pesticides provided by international agencies (alachlor, aldrin-diheldrin, atrazine, chlordane, DDT, diuron, glyphosate, lindane, mancozeb, molinate, and trifluralin) and estimated the number of cancer cases attributable to drinking water contamination by pesticides. Also, we correlated such findings with incidence and mortality cancer rates for ten topographies obtained from the Brazilian National Cancer Institute (INCA) database. A total of 9 cities were selected, corresponding to about 81,000 people. All towns had all pesticides quantified in the drinking water. About ten cancer cases were attributed to drinking water contamination by pesticides in 2014–2017, mainly linked to diuron and mancozeb. Concerning the consolidated incidence of cancer cases reported by the INCA, significant correlations were found regarding aldrin-diheldrin, alachlor, and atrazine for breast cancer, atrazine for prostate cancer, and mancozeb and diuron for colon cancer, among others. Regarding the consolidated mortality rates, some correlations were found between DDT and trifluralin for the breast, DDT and lindane for the prostate, and glyphosate for lung cancer. Moderate correlations were found between the estimated and consolidated cancer cases for several topographies. Our findings highlight the correlation between drinking water contamination in Paraná state southwest and its increased incidence of cancers with poor prognosis. Full article

The study aimed to estimate the prevalence of skin problems in children and adolescents with type 1 diabetes (T1D) using insulin pumps (IPs) and/or continuous glucose monitoring (CGM) in our center and analyze their association with various factors. As part of the international ISPAD JENIOUS-initiated SKIN-PEDIC project, we interviewed and examined patients who visited the regional pediatric diabetes center in Opole (Poland) for four weeks regarding the use of IP and/or CGM and the presence of skin problems. Body mass index (BMI) and glycemic parameters were obtained retrospectively from medical records. Among 115 individuals (45.2% girls, 83.5% IP users, 96.5% CGM users), old scars were the most common skin problem (IP users 53.1%; CGM users 66.4%), while ≥2 types of skin problems co-occurred (IP users 40.6%; CGM users 27.3%). Longer IP use was associated with a higher prevalence of skin problems (50% for IP < 1 year, 98.1%-IP 1–3 years, 100% for IP > 3 years; p < 0.001), pointing out extra attention with IP use > 1 year. No significant associations were found between skin problems and gender, age, BMI centile and glycemic parameters. Dermatological complications were common among children using IP and CGM in our center, highlighting the need for vigilant monitoring and early intervention to manage these skin-related issues effectively. Full article

Introduction: Fluvoxamine is used in children and adolescents (‘youths’) for treating obsessive compulsive disorder (OCD) but also off-label for depressive and anxiety disorders. This study aimed to investigate the relationship between fluvoxamine dose and serum concentrations, independent correlates of fluvoxamine concentrations, and a preliminary therapeutic reference range (TRR) for youths with OCD and treatment response. Methods: Multicenter naturalistic data of a therapeutic drug monitoring service, as well as prospective data of the ‘TDM Vigil study’ (EudraCT 2013-004881-33), were analyzed. Patient and treatment characteristics were assessed by standardized measures, including Clinical Global Impressions—Severity (CGI-S) and —Change (CGI-I), with CGI-I of much or very much improved defining treatment response and adverse drug reactions using the Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale. Multivariable regression analysis was used to evaluate the influence of sex, age, body weight, body mass index (BMI), and fluvoxamine dose on fluvoxamine serum concentrations. Results: The study included 70 youths (age = 6.7–19.6 years, OCD = 78%, mean fluvoxamine dose = 140.4 (range = 25–300) mg/d). A weak positive correlation between daily dose and steady-state trough serum concentrations was found (r_s = 0.34, p = 0.004), with dose variation explaining 16.2% of serum concentration variability. Multivariable correlates explaining 25.3% of the variance of fluvoxamine concentrations included higher fluvoxamine dose and lower BMI. Considering responders with OCD, the estimated TRR for youths was 55–371 ng/mL, exceeding the TRR for adults with depression of 60–230 ng/mL. Discussion: These preliminary data contribute to the definition of a TRR in youth with OCD treated with fluvoxamine and identify higher BMI as a moderator of lower fluvoxamine concentrations. Full article