Use of Azithromycin Attributable to Acute SARS-CoV-2 Infection.

PURPOSE: In the early stages of the COVID-19 pandemic, preliminary results that later proved to be incorrect suggested the possible efficacy of anti-infective drugs such as azithromycin for the treatment of SARS-CoV-2 infection. These preliminary data may have influenced the prescription of azithromycin. However, no individual-level data linking the use of this antibiotic to acute SARS-CoV-2 infection are available. The present analysis aims to fill this gap. METHODS: A retrospective population-based cohort design was used including patients diagnosed with SARS-CoV-2 infection in the period ranging from February 2020 to February 2022. The data source for antibiotic consumption was the drug database of outpatient prescriptions of Emilia-Romagna Region (Italy). Antibiotics were classified according to the Anatomical Therapeutic Chemical (ATC) classification system. Consumption rates and percentages of azithromycin DDDs (defined daily doses) during the acute phase of the infection were compared with a previous control period and with the post-acute phase. Analyses were stratified by four groups according to the prevalent virus variant at time of diagnosis. RESULTS: Comparing the previous control period with the acute phase of infections, the rates of azithromycin consumption (DDD per 1000 individuals per day) increased from 1.17 to 23.11, from 0.80 to 33.03, from 0.81 to 21.01, and from 1.02 to 9.76, in the pre-Alpha, Alpha, Delta, and Omicron periods, respectively. Similarly, the percentages of individuals receiving azithromycin, and the azithromycin DDDs percentages over total systemic antibiotics DDDs increased in acute phases of infection compared with control periods. The consumption rates and percentages returned to preinfection levels in the post-acute phase. In the study period, 12.9% of the use of azithromycin in the entire adult population of Emilia-Romagna was attributable to acute SARS-CoV-2 infection. CONCLUSIONS: Considering the low likelihood of bacterial coinfections, the increased azithromycin consumption in the acute phase of SARS-CoV-2 infection suggests inappropriate prescribing of this antibiotic.

The coculture of in vitro produced porcine embryos and oviductal epithelial cells improves blastocyst formation and modify embryo quality.

The efficiency of in vitro embryo production in mammals is influenced by variables associated with culture conditions during maturation, fertilization, and embryonic development. The embryos obtained often exhibit low quality due to suboptimal in vitro culture conditions compared to the in vivo environment. Co-culturing gametes and embryos with somatic cells has been developed to enhance in vitro culture conditions. This study aimed to assess the impact of coculturing in vitro-produced porcine embryos with porcine oviductal epithelial cells (POEC) on embryo development and quality. Firstly, a pure culture of POEC suitable for coculture systems was established. The epithelial origin of the cells was confirmed by the expression of E-cadherin and cytokeratin. The expression pattern of hormone receptors aligned with the diestrous oviduct, and POEC also secreted oviductal glycoprotein type 1 (OVGP-1). Secondly, POEC from passage 1 (POEC-1) were used to coculture with in vitro-produced porcine embryos. A successful coculture system was established without the addition of fetal bovine serum as a supplement. Coculturing POEC-1 in monolayers with in vitro-produced porcine embryos during the initial two days of culture enhanced the percentage of blastocysts and their hatching. Although the coculture did not alter the number of cells in the blastocysts or apoptosis assessed by TUNEL, it significantly reduced reactive oxygen species (ROS) levels in cleaved porcine embryos. This study represents the first report evaluating the quality of porcine embryos produced by IVF in coculture systems and assessing ROS levels in cleaved porcine embryos obtained by IVF.

Oro-dental manifestations of eating disorders: a systematic review.

BACKGROUND: Eating disorders (EDs) pose a significant risk to health, especially when not diagnosed early. For several years EDs and oral health has been extensively studied, and now it is quite clear the existence of a correlation between specific oral manifestations and these disorders. While these oral signs could potentially aid early diagnosis of EDs, their identification and the eventual establishment of a correlation is currently heavily limited to the clinician's experience. The present systematic review critically examines existing literature, offering an updated overview of oro-dental manifestations associated with EDs. METHOD: MEDLINE (via PubMed), Web of Science, Scopus, and grey literature were searched, and relevant epidemiological comparative studies were screened using the Rayyan software. No limitations have been imposed on the research regarding oro-dental outcomes, encompassing all medically diagnosed EDs. The quality of the studies was valuated using AXIS appraisal tool for cross-sectional studies. RESULT: Out of 3990 studies, 32 fulfilled the eligibility criteria and were included in the synthesis. The identified eating disorders include Anorexia Nervosa, Bulimia Nervosa and/or Eating Disorders Not Otherwise Specified, predominantly among female subjects, primarily originating from Europe. The evaluated oro-dental outcomes include dental erosion, caries, saliva assessment, hygiene-periodontal parameters, and mucosal tissue appearance. The association with erosion is confirmed while gingival recession, dentinal hypersensitivity, salivary flow thresholds and aspects relating to oral pathology are receiving increasing support from emerging evidence. DISCUSSION: This trend emphasizes the critical role of the complete intraoral examination to detect significant oro-dental signs that may indicate the onset of an ED.

The article is a review of existing studies that explores the link between eating disorders and oral health issues. It found that people with eating disorders, including anorexia nervosa and bulimia nervosa, may experience dental problems such as tooth erosion, cavities, and altered saliva production. The review findings emphasize the importance of dental care providers recognizing these signs early and suggests better training for dental professionals. By doing so, they can help diagnose eating disorders sooner and recommend appropriate treatment. This approach aims to improve patients' overall wellbeing by addressing both the oral health issues and the underlying eating disorders, making it essential for patients and medical teams to be aware of the interconnectedness between oral health and eating disorders.

Infectious events in patients with alopecia areata treated with JAK inhibitors: low burden and minimal impact on persistence in treatment.

BACKGROUND: Alopecia areata (AA) is a non-scarring disorder characterized by hair loss that greatly affects patients' quality of life and has a chronic, recurring course. This disease is marked by an inflammatory process, mainly on an autoimmune basis primarily regulated by Janus kinase (JAK). RESEARCH DESIGN AND METHODS: We conducted a retrospective study evaluating the safety of JAKi in a real-world setting in 91 AA patients, with a specific focus on the assessment of infectious events. RESULTS: Overall, 34 infectious events were observed in 28 patients (30.8%), among them 17 patients (60.7%) suspended treatment with JAKi until the infection was clinically resolved. Only in one case the infectious event led to a permanent discontinuation of the treatment. The data we observed in the study are consistent with results reported in clinical trials. CONCLUSION: It can be stated that, during treatment with JAKi in AA patients, infectious events may occur, but in most cases these events are easily manageable and do not result in permanent discontinuation of the drug.

Plasmodium RNA triphosphatase validation as antimalarial target.

Target-based approaches have traditionally been used in the search for new anti-infective molecules. Target selection process, a critical step in Drug Discovery, identifies targets that are essential to establish or maintain the infection, tractable to be susceptible for inhibition, selective towards their human ortholog and amenable for large scale purification and high throughput screening. The work presented herein validates the Plasmodium falciparum mRNA 5' triphosphatase (PfPRT1), the first enzymatic step to cap parasite nuclear mRNAs, as a candidate target for the development of new antimalarial compounds. mRNA capping is essential to maintain the integrity and stability of the messengers, allowing their translation. PfPRT1 has been identified as a member of the tunnel, metal dependent mRNA 5' triphosphatase family which differs structurally and mechanistically from human metal independent mRNA 5' triphosphatase. In the present study the essentiality of PfPRT1 was confirmed and molecular biology tools and methods for target purification, enzymatic assessment and target engagement were developed, with the goal of running a future high throughput screening to discover PfPRT1 inhibitors.

Design, clinical applications and post-surgical assessment of bioresorbable 3D-printed craniofacial composite implants.

This study details the design, fabrication, clinical trials' evaluation, and analysis after the clinical application of 3D-printed bone reconstruction implants made of nHAp@PLDLLA [nanohydroxyapatite@poly(L-lactide-co-D,L-lactide)] biomaterial. The 3D-printed formulations have been tested as bone reconstruction Cranioimplants in 3 different medical cases, including frontal lobe, mandibular bone, and cleft palate reconstructions. Replacing one of the implants after 6 months provided a unique opportunity to evaluate the post-surgical implant obtained from a human patient. This allowed us to quantify physicochemical changes and develop a spatial map of osseointegration and material degradation kinetics as a function of specific locations. To the best of our knowledge, hydrolytic degradation and variability in the physicochemical and mechanical properties of the biomimetic, 3D-printed implants have not been quantified in the literature after permanent placement in the human body. Such analysis has revealed the constantly changing properties of the implant, which should be considered to optimize the design of patient-specific bone substitutes. Moreover, it has been proven that the obtained composition can produce biomimetic, bioresorbable and bone-forming alloplastic substitutes tailored to each patient, allowing for shorter surgery times and faster patient recovery than currently available methods.

Sarcopenia Prevalence among Hospitalized Patients with Severe Obesity: An Observational Study.

Background: Sarcopenic obesity (SO) is the combination of excess fat, skeletal muscle and muscular strength/function deficit. The ESPEN/EASO have proposed new diagnostic criteria, but the SO prevalence in patients with severe obesity remains to be established. The aim of this study was to establish the SO prevalence in a large cohort of inpatients with obesity, considering sex, age, BMI, type, and number of concomitant diseases. Methods: Patient data of both genders aged between 18 and 90 years with a body mass index (BMI) of ≥30 kg/m2 underwent hospital evaluation including bioelectrical impedance analysis (BIA) and handgrip strength (HS). QoL scores were obtained by the Psychological General Well-Being Index questionnaire. The study was approved by the institutional Ethic Committee. Results: Among the 3858 patients, 444 (11.51%) exhibited a strength deficit, while 3847 (99.71%) had skeletal muscle mass deficit. The prevalence of SO was then 11.48%, with higher rates in women (12.39%), in individuals aged >70 years (27%), and in those reporting a 'poor' QoL (12.6%). No significant difference in SO prevalence was found when stratifying by BMI (30-40 kg/m2 vs. >40 kg/m2, p = 0.1710). In SO patients, osteoarticular diseases (57%), hypertension/heart failure (38%), type 2 diabetes mellitus (34%), and obstructive sleep apnea (32%) were the more frequent comorbidities. Conclusions: The application of ESPEN/EASO-SO criteria in a cohort of inpatients with severe obesity revealed 11.48% SO prevalence, which was associated with age (particularly > 70 years), gender (women), but not BMI, as determinants. Disease staging and QoL screening may improve the identification of SO high-risk patients.

Neophobia, sensory experience and child's schemata contribute to food choices.

PURPOSE: The aim of the present review is to analyze dynamic interactions between nutrigenomics, environmental cues, and parental influence, which can all lead to children's neophobic reactions and its persistence in time. METHODS: We reviewed studies available on electronic databases, conducted on children aged from birth to 18 years. We also considered official websites of Italian Institutions, providing advice on healthy eating during infancy. RESULTS: Modern day societies are faced with an eating paradox, which has severe and ever-growing implications for health. In face of a wider availability of healthy foods, individuals instead often choose processed foods high in fat, salt and sugar content. Economic reasons surely influence consumers' access to foods. However, there is mounting evidence that food choices depend on the interplay between social learning and genetic predispositions (e.g., individual eating traits and food schemata). Neophobia, the behavioral avoidance of new foods, represents an interesting trait, which can significantly influence children's food refusal. Early sensory experiences and negative cognitive schemata, in the context of primary caregiver-child interactions, importantly contribute to the priming of children's food rejection. CONCLUSIONS: As neophobia strongly affects consumption of healthy foods, it will be relevant to rule definitively out its role in the genesis of maladaptive food choices and weight status in longitudinal studies tracking to adulthood and, in meanwhile, implement early in life effective social learning strategies, to reduce long-term effects of neophobia on dietary patterns and weight status. LEVEL OF EVIDENCE: Level II, controlled trials without randomization.

In Situ Use of Mining Substrates for Wetland Construction: Results of a Pilot Experiment.

This paper evaluates an experimental wetland as part of a pilot soil reclamation project in a mining area. The wetland was constructed using materials of mining origin from the area; most reactive materials of acid pH were stabilised using limestone filler. The study selected macrophytes that are tolerant to potentially toxic elements (PTEs) and resistant to salinity, namely Phragmites australis, Juncus effusus, and Iris pseudacorus. These macrophytes were then placed in pots containing substrates composed of different mixtures of topsoil, peat, and mining waste (black or yellow sand). A thorough analysis of the physicochemical and mineralogical characteristics of the materials included studies of PTE mobilisation. This study emphasises the significance of the rhizosphere in directing the transfer of PTEs to the plant and the correlation between the substrate and the development of plant defence mechanisms, such as the formation of Fe-plates. Scanning electron microscopy was used to highlight these aspects and validate the results of the analytical determinations. These wetlands can be proposed as a phytoremediation strategy for areas affected by mining and maritime influence. They are easy to construct and remain stable, providing important ecosystem services such as the natural attenuation of acid mine drainage, support for vegetation development and fauna, and a clean ecosystem.

Complete remission with histamine blocker in a patient with intractable hyperadrenergic postural orthostatic tachycardia syndrome secondary to long coronavirus disease syndrome.

The COVID-19 pandemic caused by the novel severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has emerged as a global public health concern and its sequels have barely started to outcrop. A good percentage of patients who suffered from COVID-19 are prone to develop long-COVID or post-COVID condition (PCC), a multisystemic, heterogeneous, chronic disorder. Patients with PCC may experience diverse manifestations, of which cardiovascular and neurological symptoms are among the most frequently reported. Indeed, dysautonomia presented as orthostatic intolerance has gained room following recent reports linking postural orthostatic tachycardia syndrome (POTS) with PCC. Disturbances in heart rate (HR) and blood pressure (BP) during postural changes are the cornerstones of orthostatic intolerance seen in patients suffering from PCC. A subtype of POTS, hyperadrenergic POTS, has been widely studied because of its association with mast cell activation syndrome (MCAS). Although a causative relationship between PCC, hyperadrenergic POTS, and MCAS remains unrevealed, these syndromes can overlap. We want to propose here a correlation produced by a close-loop mechanism with positive feedback established after SARS-CoV-2 infection in a previously healthy young patient.

A case report of LAI two injection start in a 16-year-old adolescent with severe manic episode and comorbid cannabinoid use disorder.

There is a lack of randomized clinical trials and few studies regarding long-acting injectable antipsychotics (LAIs) in adolescents. Non-adherence, aggressiveness, comorbid substance use disorder and lack of insight may represent the main reasons for starting LAIs. Hereby we describe a 16-year-old male adolescent subject with bipolar type I disorder and comorbid cannabinoid use disorder, successfully treated with two-injection start regimen of LAI aripiprazole. Two-injection start regime of aripiprazole could represent an effective and safe therapeutic option for adolescents with early onset bipolar disorder.

Food Compass and the challenge of sustainability on the route towards healthful diets.

In order to tackle the global increase in overweight and obesity prevalence, several nutrient profiling systems have been developed; among others, Food Compass Score (FCS) has been designed to encompass multiple domains of food healthfulness. However, environmental sustainability of healthy diets is another crucial dimension which should not be overlooked in the context of human health. The aim of the present study is to assess the association between healthiness and environmental sustainability of food items, using the FCS and Agribalyse databases, respectively. A total of 806 matching food items were identified, grouped in 12 food categories; within each category, differences in median Z-scores between FCS and Single Environmental Footprint (EF) Score were assessed. While Fruits, Legumes and Nuts, Mixed foods, Meat Poultry and Eggs (MPE), Savory and Sweets, and Vegetables showed statistically significant differences (all p < 0.001), Beverages (p = 0.361), Dairy (p = 0.092), Fats and Oils (p = 0.594), Grains (p = 0.436), Sauce and Condiments (p = 0.093), and Seafood (p = 0.241) had similar Food Compass and Single EF Z-scores distributions. These findings underscore a relevant lack of difference between healthfulness and environmental impact of some prominent food categories, such as Grains and Seafood. Therefore, we suggest matching nutrient profiling systems with adequate environmental sustainability indices.

DNA methylation profiling of myelodysplastic syndromes and clinical response to azacitidine: A multicentre retrospective study.

Real-world data have revealed that a substantial portion of patients with myelodysplastic syndromes (MDS) does not respond to epigenetic therapy with hypomethylating agents (HMAs). The cellular and molecular reasons for this resistance to the demethylating agent and biomarkers that would be able to predict the treatment refractoriness are largely unknown. In this study, we shed light on this enigma by characterizing the epigenomic profiles of patients with MDS treated with azacitidine. Our approach provides a comprehensive view of the evolving DNA methylation architecture of the disease and holds great potential for advancing our understanding of MDS treatment responses to HMAs.

Sarcopenic obesity and the impact on bone health.

PURPOSE OF REVIEW: Sarcopenic obesity is a newly identified pathological entity defined by an increase in body fat mass with an associated sarcopenia, characterized by loss of muscle mass, strength, and function. Recently, the concomitant presence of skeletal alteration with sarcopenic obesity has been described leading to a new clinical entity defined osteosarcopenic obesity (OSO). Many studies have tried to unravel the metabolic complex mechanism leading to this clinical entity in order to understand the pathophysiology of this complex condition with the aim of posing an early diagnosis to improve the therapeutic approaches. The purpose of this narrative review is to highlight and revise recent studies on this issue. RECENT FINDINGS: Recent research in the field of OSO has highlighted the role of nutrition and physical activity in the development and management of these conditions. While molecular and cellular pathways remain partially understood, there is a growing focus on lifestyle interventions as key factors in reducing the impact of OSO. These studies emphasize the need for early diagnosis and appropriate therapeutic strategies to improve quality of life and decrease morbidity and mortality associated with OSO. SUMMARY: Although the pathophysiological pathways underlying OSO are not fully understood, the clinical implications underscore the need for expanded research in this field. This research is crucial for enabling early diagnosis and implementing effective therapeutic interventions, with the goal of reducing morbidity and mortality and enhancing quality of life.

Zinner syndrome in pediatric patients: rare disease leading to challenging management.

Introduction: Zinner syndrome (ZS) is the association of seminal vesicle cysts, ipsilateral ejaculatory duct obstruction, and ipsilateral renal agenesis. This condition is very rare in children and both diagnosis and treatment may be challenging. We reviewed the clinical presentation and treatment describing our experience with a series of three patients. Methods: From January 2016 to January 2021, three patients (patients 1, 2, and 3) with symptomatic ZS, aged 2, 15, and 17 years, respectively, were diagnosed and treated. All three patients were symptomatic, manifesting pelvic pain and dysuria. The diagnosis was made by physical examination, ultrasonography, and abdominopelvic MRI. Patient 1 underwent open surgery, while for patients 2 and 3, laparoscopic excision was performed. Results: The renal agenesis regarded the left side in patients 1 and 3, and the right side in patient 2. In all cases, the cystic complex was excised. The mean operating time was 4 h and the mean hospitalization time was 5 days (range 4-6 days). The mean follow-up period was 5 years (range 2-5 years). Patients 1 and 3 showed a complete resolution of the symptoms during postoperative follow-up. In patient 2, clinical symptoms relapsed because of the persistence of a 9 mm cyst requiring a redo laparoscopic excision. Conclusions: Seminal vesicle cyst with ipsilateral renal agenesis, even if rare in pediatric age, should be suspected in young male patients presenting with pelvic cystic masses, pelvic pain, dysuria, and ipsilateral renal absence. Conservative management should be reversed to asymptomatic patients. Surgical treatment is mandatory in symptomatic cases and the preferred approach is minimally invasive surgery to magnify the operating field to spare anatomical structures, primarily the contralateral vas deferens. Radicality is crucial to avoid the persistence of symptoms and the need for reintervention.

Analysis of internal heat recovery capability in air-cooled indirect fired GAX-based absorption chiller in part-load operation.

Single-effect absorption chillers are the most popular because of their low cost, despite their low COP. Among them, GAX-based AirCooled absorption chillers are very interesting because they have improved COP because of their ability to recover internal heat at low thermal lifts. This workshop analysed the ability of these types of chillers to recover internal heat at high thermal lifts by changing the pressure drop of an extra valve, a feature of the Robur absorption chiller when operating in subzero applications. The complete differential mathematical model analyses the components involved in heat supply and recovery and provides information on their operation. A thorough assessment of exergy destruction in the absorption refrigeration system was carried out. The main results show that when the chiller is driven at a temperature of 210 °C and an ambient temperature of 40 °C, a rise in the pressure drop of the additional valve, ΔPval1, from 175 to 700 kPa causes the extension of the vapour purification process to be reduced by 13.7% in the column of distillation and by 70.6% in the rectifier. Despite the adverse effect of ΔPval1 increase on the cooling capacity, there is no risk that the distillation column operates in weeping mode. However, this adjustment increases the internal thermal load of the generator by 26.9%. Furthermore, the mass fraction of the refrigerant flow is very similar. In addition, the occurrence of a two-phase solution flow at the input of a solution cooling absorber is the practical upper limit of ΔPval1. The refrigerant flow in the solution cooling absorber is reduced by 21.3%. Finally, the contribution of the heat recovery loop to the total exergy destruction in the refrigeration system rises slightly by 2.7% when ΔPval1 increases due to the contribution of the vapour purification system, which increases at the expense of that of the re-boiler and the SolutionCooled absorber. The results of this study show to what extent the modified GAX-based cycle can function effectively at high thermal lifts.

Symptomatic gallstone disease: Recurrence patterns and risk factors for relapse after first admission, the RELAPSTONE study.

BACKGROUND: Delayed cholecystectomy in patients with symptomatic gallstone disease is associated with recurrence. Limited data on the recurrence patterns and the factors that determine them are available. OBJECTIVE: We aimed to determine the pattern of relapse in each symptomatic gallstone disease (acute pancreatitis, cholecystitis, cholangitis, symptomatic choledocholithiasis, and biliary colic) and determine the associated factors. METHODS: RELAPSTONE was an international multicenter retrospective cohort study. Patients (n = 3016) from 18 tertiary centers who suffered a first episode of symptomatic gallstone disease from 2018 to 2020 and had not undergone cholecystectomy during admission were included. The main outcome was relapse-free survival. Kaplan-Meier curves were used in the bivariate analysis. Multivariable Cox regression models were used to identify prognostic factors associated with relapses. RESULTS: Mean age was 76.6 [IQR: 59.7-84.1], and 51% were male. The median follow-up was 5.3 months [IQR 2.1-12.4]. Relapse-free survival was 0.79 (95% CI: 0.77-0.80) at 3 months, 0.71 (95% CI: 0.69-0.73) at 6 months, and 0.63 (95% CI: 0.61-0.65) at 12 months. In multivariable analysis, older age (HR = 0.57; 95% CI: 0.49-0.66), sphincterotomy (HR = 0.58, 95% CI: 0.49-0.68) and higher leukocyte count (HR = 0.79; 95% CI: 0.70-0.90) were independently associated with lower risk of relapse, whereas higher levels of alanine aminotransferase (HR = 1.22; 95% CI: 1.02-1.46) and multiple cholelithiasis (HR = 1.19, 95% CI: 1.05-1.34) were associated with higher relapse rates. CONCLUSION: The relapse rate is high and different in each symptomatic gallstone disease. Our independent predictors could be useful for prioritizing patients on the waiting list for cholecystectomies.

3D-4K Exoscope-Assisted CO2 Laser Supraglottoplasty for Severe Laryngomalacia in a Pediatric Patient.

Laryngomalacia is the most frequent congenital laryngeal anomaly. Surgery is possible by means of cold knife, carbon dioxide (CO2 ) laser, microdebrider and coblation, traditionally under microscopic view. We here describe the use of the 3D-4K exoscope assisted CO2 laser supraglottoplasty in tubeless general anesthesia in spontaneous breathing in a 5 month-old patient with severe laryngomalacia. Laryngoscope, 134:1359-1362, 2024.