New Insights of Target Therapy: Effects of Tyrosine Kinase Inhibitors on Male Gonadal Function: A Systematic Review.

The number of cancer patients undergoing chronic treatment with target therapy is increasing. Although much is known about the toxicity of conventional anticancer therapies, evidence on the effects of tyrosine kinase inhibitors (TKIs) on fertility is still lacking. Therefore, this review was undertaken to evaluate the effects of TKIs on male gonadal function. A comprehensive search of PubMed and Scopus databases was conducted, focusing on the effects of TKIs on spermatogenesis and testicular endocrine function. We included animal studies, observational studies, and case reports published up to December 31, 2023. Identified articles were reviewed and analyzed to evaluate the impact of TKIs on the male gonad. Their long-term effects, the reversibility of the observed changes, and the underlying molecular mechanisms involved were recorded. The findings emerging on the effects of TKIs on male gonadal function are conflicting. Although specific TKIs (imatinib, gefitinib, sorafenib, sunitinib, quizartinib, dasatinib, and nilotinib) have been identified as potentially as potential interfering with spermatogenesis and hormone production, the extent and severity of these effects may vary from patient to patient and between different drugs within this drug class. Experimental studies on mouse models have suggested a potential interference with spermatogenesis. Evidence also suggests that TKIs affects the hypothalamic-pituitary-testicular axis, decreasing serum testosterone and gonadotropin levels. The effects of TKIs on male gonadal function highlight the need for personalized treatment choices. Potential fertility concerns can help minimize adverse effects and improve patient outcomes. Addressing the potential impact of TKIs on male fertility helps optimize cancer treatment and survival outcomes.

Impact of COVID-19 on testicular function: a systematic review and meta-analysis.

INTRODUCTION: Studies investigating the effects of SARS-CoV-2 on male reproductive function are few and heterogeneous, and results are often conflicting. This systematic review and meta-analysis was carried out on studies conducted in men with active or anamnestic SARS-CoV-2 infection to evaluate its consequences on the male sex hormone profile and semen parameters. MATERIALS AND METHOD: This meta-analysis follows the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocols. PubMed, Scopus, Cochrane, and Embase databases were searched to identify relevant studies. We originally selected 3553 articles. After the eligibility phase, 16 articles met our inclusion criteria encompassing 11 case-control studies and 5 cohort studies (2 prospective and 3 retrospective studies). We performed the quantitative analysis with Comprehensive Meta-Analysis Software. Cochran-Q and heterogeneity (I2) indexes were used to assess statistical heterogeneity. Sensitivity analysis and publication bias tests were also performed. RESULTS: Overall, 1250 patients with active or recent (up to 80 days before) COVID-19 infection and 1232 matched healthy controls were included. Sperm concentration, total sperm count, and total motility were significantly lower in patients compared with controls. Patients also showed lower levels of total testosterone and follicle-stimulating hormone, and higher levels of luteinizing hormone, 17ß-estradiol, and prolactin compared with healthy controls. None of the included studies found the presence of SARS-CoV-2 mRNA in the semen of infected patients. CONCLUSION: The present systematic review and meta-analysis suggests the presence of an association between SARS-CoV-2 infection and primary testicular damage manifested with a picture of altered steroidogenesis and worsening spermatogenesis. The absence of the virus in the seminal fluid indicates a low possibility of sexual transmission of the infection to partners and offspring. However, our findings mostly show short-term follow-up, while few studies have considered the long-term consequences of the viral infection, thus further studies are needed to evaluate the long-term consequences on male reproductive health.

The Role of Irisin throughout Women's Life Span.

Since its discovery, much attention has been drawn to irisin's potential role in metabolic and reproductive diseases. This narrative review summarizes and updates the possible role played by this fascinating molecule in different physiological (puberty and menopause) and pathological (polycystic ovary syndrome (PCOS), functional hypothalamic amenorrhea (FHA), endometriosis, and gestational diabetes) conditions that can affect women throughout their entire lives. Irisin appears to be an important factor for the hypothalamic-pituitary-gonadal axis activation, and appears to play a role in the timing of puberty onset. Serum irisin levels have been proposed as a biomarker for predicting the future development of gestational diabetes (GDM). Its role in PCOS is still controversial, although an "irisin resistance" mechanism has been hypothesized. In addition to its impact on metabolism, irisin also appears to influence bone health. Irisin levels are inversely correlated with the prevalence of fractures in postmenopausal women. Similar mechanisms have also been postulated in young women with FHA. In clinical settings, further controlled, prospective and randomized clinical trials are needed to investigate the casual relationship between irisin levels and the conditions described and, in turn, to establish the role of irisin as a prognostic/diagnostic biomarker or a therapeutic target.

Impact of COVID-19 on Fetal Outcomes in Pregnant Women: A Systematic Review and Meta-Analysis.

Background: Coronavirus disease (COVID-19) is a pandemic causing respiratory symptoms, taste alterations, olfactory disturbances, and cutaneous, cardiovascular, and neurological manifestations. Recently, research interest has shifted to reproductive health to understand the factors predisposing to COVID-19 infection in pregnancy, the consequences of the infection on the fetus and on the mother, and possible vertical transmission through the placenta. Pregnancy does not increase the risk of SARS-CoV-2 infection, according to studies. However, contrary to non-pregnant women, pregnancy worsens the clinical outcome of COVID-19. Studies investigating the effects of COVID-19 on pregnancy women are heterogeneous, and the results are often conflicting. Objectives: The goal of the current work was to offer a thorough and up-to-date systematic review of, and meta-analysis on, the impact of COVID-19 on ovarian function, pregnancy, and fetal outcomes. Search strategy: This meta-analysis (PROSPERO n. CRD42023456904) was conducted using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocols. The search for relevant material was conducted using PubMed, Scopus, Cochrane, and Embase databases, through to 15 December 2022. Selection criteria: Original articles on fertile pregnant women or women attempting to become pregnant, with an active case of, or history of, SARS-CoV-2 infection were included, and reproductive function was compared to that of uninfected women. Data collection and analysis: The effects of COVID-19 on female reproductive function, particularly ovarian function, the profile of female sex hormones, pregnancy outcomes and fetal outcomes were the focus of our search. Quantitative analysis was performed with Comprehensive Meta-Analysis Software. The standard difference of the mean was calculated for the statistical comparison between cases and controls. Cochran's Q test and heterogeneity (I2) indexes were used to assess statistical heterogeneity. Sensitivity analysis and publication bias tests were also performed. Main Results: Twenty-eight articles met our inclusion criteria, for a total of 27,383 patients pregnant or looking to have offspring, with active or anamnestic COVID-19, and 1,583,772 uninfected control women. Our study revealed that there was no significant difference between COVID-19 patients and the control group in terms of maternal characteristics such as age, body mass index (BMI) and comorbidities that could affect pregnancy and fetal outcomes. The risk of a miscarriage or Cesarean delivery was significantly lower, while the risk of fetal death or premature delivery was significantly higher in COVID-19 patients than in the controls. None of the included studies evaluated hormonal profiles or investigated the presence of infertility. Conclusions: Maternal comorbidities, age, and BMI do not raise the risk of COVID-19. However, pregnant women with COVID-19 had a lower risk of miscarriage and Cesarean delivery, possibly because of better prenatal care and high levels of observation during labor. COVID-19 during pregnancy increases the risk of fetal death and premature delivery.

A Regressive Model to Study the Hospitalization for Laparoscopic Appendectomy: A Multicenter Study.

Appendicitis is a most common abdominal condition worldwide, and appendectomy especially laparoscopic appendectomy is among the most commonly performed general surgeries. In this study, data were collected from patients who underwent laparoscopic appendectomy surgery at the Evangelical Hospital "Betania" in Naples, Italy. Linear multiple regression was used to obtain a simple predictor that can also assess which of the independent variables considered to be a risk factor. The model with R2 of 0.699 shows that comorbidities and complications during surgery are the main risk factors for prolonged LOS. This result is validated by other studies conducted in the same area.

Effect of Clinical and Demographic Variables on the Hospital Stay of Patients Undergoing Total Knee Arthroplasty.

The knee is the joint most affected by osteoarthritis and in its severe form can significantly affect people's physical and functional abilities. The increased demand for surgery leads to greater attention by health care management to be able to keep costs down. A major expense item for this procedure is Length of Stay (LOS). In this study, several Machine Learning algorithms were tested in order to construct not only a valid predictor of LOS but also to know among the selected variables the main risk factors. To do so, activity data from the Evangelical Hospital "Betania" in Naples, Italy, from 2019-2020 were used. Among the algorithms, the best are the classification algorithms with accuracy values exceeding 90%. Finally, the results are in line with those shown by two other comparison hospitals in the area.

The Classification Algorithms Applied to the Inpatient Stay for Lower Limb Surgery.

The revolutions of recent years in health care have involved several areas ranging from patient treatment to resource management. Therefore, several strategies have been put in place to increase patient value while trying to reduce spending. Several indicators have arisen to evaluate the performance of healthcare processes. The main one is Length of Stay (LOS). In this study, classification algorithms were used to predict the LOS of patients undergoing lower extremity surgery, an increasingly common condition given the progressive aging of the population. The context is the Evangelical Hospital "Betania" in Naples (Italy) in 2019-2020, which augments a multicenter study conducted by the same research team on several hospitals in southern Italy. All selected algorithms show an Accuracy above 90% but among them, the best is Logistic Regression with a value reaching 94%.

Modeling Cholecystectomy Hospital Stay Through a Linear Approach.

Cholecystectomy is among the most frequent procedures in general surgery. In the healthcare facility organization, it is important to evaluate all interventions and procedures that have a great impact on health management and that have a clear effect on the Length of Stay (LOS). The LOS represents, in fact, an indicator of performance and measure the goodness of a health process. This study was conducted with the aim of providing LOS for all patients undergoing cholecystectomy at the "A.O.R.N. A. Cardarelli" of Naples. Data were collected in the two years 2019 and 2020 and included 650 patients. A MLR model is created in the work to predict the value of LOS as a function of the following variables: gender, age, pre-operative LOS, presence of comorbidities and complication during surgery. The results obtained are as follows: R=0.941 and R2=0.885.

Prediction of Hospital Length Stay for Patients Undergoing Mastectomy.

The prolonged length of stay is an important aspect to be considered for the healthcare management since this affect both the health-related expenditure of the hospital and the quality of the offered service. In the light of these consideration is important for hospitals to be able to predict the LOS of patients and to work on the principal aspect affecting it in order to reduce LOS as much as possible. In this work we focus on patients undergoing mastectomy. The data were collected form 989 patients who underwent mastectomy surgery in the Surgery Department of the AORN "A. Cardarelli" of Naples. Different models have been tested and characterized and the one with the best performance was identified.

COVID-19 in Eye Surgery: The Case of a University Hospital.

Coronavirus epidemic has quickly become a global health threat. The ophthalmology department, like all other departments, have adopted resource management and personnel adjustment maneuvers. The aim of this work was to describe the impact of covid on the Ophthalmology Department of University Hospital "Federico II" of Naples. In the study logistical regression was used for a comparison between the pandemic and the previous period, analyzing patient features. The analysis showed a decrease in the number of accesses; reduction of the length of stay; and the statistically dependent variables are as follows: LOS, discharge procedures and admission procedure.

Predicting In-Hospital Mortality During the COVID-19 Pandemic in Patients with Heart Failure: A Single-Center Exploratory Study.

The aim of this study was to investigate whether exposure to the pandemic was associated with increased in-hospital mortality for health failure. We collected data from patients hospitalized between 2019 and 2020 and we assessed the likelihood of in-hospital death. Although the positive association of exposure to the COVID period with an increased in-hospital mortality is not statistically significant, this may underscore other factors that may influence mortality. Our study was designed to contribute to a better understanding of the impact of the pandemic on in-hospital mortality and to identify potential areas for intervention in patient care.

Is It Time for Andrology and Endocrinology Professionals in Assisted Reproduction Centers?

Epidemiologists indicate that about half of the couple's infertility cases are due to a male factor. Despite this, the role of andrologists or endocrinologists in assisted reproductive technique (ART) centers is still underestimated. According to our literature review, this reduces the chance of a thorough clinical evaluation of the male partners, which, sometimes consists only in a mere semen analysis, usually performed by laboratory technicians. A more complete diagnostic process could lead to the identification of potentially treatable causes of infertility, the recognition of diseases that require immediate treatment, and to the discovery of genetic diseases and, therefore, transmissible to the offspring. It can also increase the success rate of ART resulting in less psychological and financial burden for both public health resources and infertile couples. The presence of medical personnel with andrological and endocrinological skills in the ART centers represents the first step in creating 'precision medicine'. We hope that the guidelines of the various scientific societies will clearly contemplate this possibility.

Evaluation of different machine learning algorithms for predicting the length of stay in the emergency departments: a single-centre study.

Background: Recently, crowding in emergency departments (EDs) has become a recognised critical factor impacting global public healthcare, resulting from both the rising supply/demand mismatch in medical services and the paucity of hospital beds available in inpatients units and EDs. The length of stay in the ED (ED-LOS) has been found to be a significant indicator of ED bottlenecks. The time a patient spends in the ED is quantified by measuring the ED-LOS, which can be influenced by inefficient care processes and results in increased mortality and health expenditure. Therefore, it is critical to understand the major factors influencing the ED-LOS through forecasting tools enabling early improvements. Methods: The purpose of this work is to use a limited set of features impacting ED-LOS, both related to patient characteristics and to ED workflow, to predict it. Different factors were chosen (age, gender, triage level, time of admission, arrival mode) and analysed. Then, machine learning (ML) algorithms were employed to foresee ED-LOS. ML procedures were implemented taking into consideration a dataset of patients obtained from the ED database of the "San Giovanni di Dio e Ruggi d'Aragona" University Hospital (Salerno, Italy) from the period 2014-2019. Results: For the years considered, 496,172 admissions were evaluated and 143,641 of them (28.9%) revealed a prolonged ED-LOS. Considering the complete data (48.1% female vs. 51.9% male), 51.7% patients with prolonged ED-LOS were male and 47.3% were female. Regarding the age groups, the patients that were most affected by prolonged ED-LOS were over 64 years. The evaluation metrics of Random Forest algorithm proved to be the best; indeed, it achieved the highest accuracy (74.8%), precision (72.8%), and recall (74.8%) in predicting ED-LOS. Conclusions: Different variables, referring to patients' personal and clinical attributes and to the ED process, have a direct impact on the value of ED-LOS. The suggested prediction model has encouraging results; thus, it may be applied to anticipate and manage ED-LOS, preventing crowding and optimising effectiveness and efficiency of the ED.

Expresión clínica de la COVID-19 en pediatría de atención primaria: estudio COVIDPAP / COVID-19 clinical features in primary care: COVIDPAP study

Objetivos: En España, las pruebas diagnósticas de COVID-19 en atención primaria estuvieron disponibles desde mayo de 2020. Previamente la mayoría de los estudios describían pacientes hospitalarios: la fiebre y la tos eran los síntomas más frecuentes. Interesaba conocer la expresión clínica de la COVID-19 pediátrica en la comunidad. Métodos: Estudio descriptivo analítico observacional de casos pediátricos (0-14 años) de 255 pediatras de atención primaria españoles, del 12/5/2020 al 30/4/2021. Los diagnósticos se determinaron por PCR, test rápido de detección de antígeno o serología IgG positiva. Resultados: Se incluyeron 10.021 niños, 48,4% mujeres, con una edad media de 8,04±4,17 años. Se detectó la infección por búsqueda de contactos (70,9%) o síntomas compatibles (18,8%). El hogar familiar fue la principal fuente de contagio (64,9%), seguido por los colegios (10%) o de origen desconocido (9,9%). No hubo diferencias significativas en la incidencia entre temporadas vacacionales o lectivas. El 43,2% fueron asintomáticos. Los síntomas más frecuentemente encontrados fueron rinorrea en menores de 2 años, fiebre entre 3 y 8 años y cefalea en mayores de 9 años. Se describen exhaustivamente los síntomas y signos observados por edad. Se hospitalizaron a 8 pacientes, uno con un síndrome inflamatorio multisistémico. No hubo fallecimientos. Conclusiones: La COVID-19 es una enfermedad leve con un gran número de casos asintomáticos, con pocas hospitalizaciones y fallecimientos. El lugar principal de transmisión es el domicilio y el cierre de colegios debería ser el último recurso para controlar la pandemia. No se pudo describir un cuadro clínico característico de la enfermedad. (AU)

Objectives: In Spain, the tools to diagnose COVID-19 were available in primary care from May 2020. Previously most studies described inpatients, and fever and cough were the most frequent symptoms. This study aims to define the clinical picture of the pediatric COVID-19 in the community. Methods: A descriptive and analytical observational study was performed including pediatric cases (0-14y) from 255 pediatricians, proportionally distributed to its population, from primary health centers in Spain, from 12th May 2020 to 30th April 2021. Diagnostics were made by PCR detection of viral RNA, rapid antigen detection test or positive IgG serology. Results: There were 10,021 positive children included, 48.4% women, mean age 8,04±4.17 years. Infection was detected due to contact tracing (70.9%), compatible symptoms (18.8%). Household was the main source of transmission (64.9%), followed by school setting (10%) or unknown (9.9%). We did not find any significant differences in the incidence between holidays and school terms. 43.2% of the children were asymptomatic. Most frequent symptoms are rhinorrhea in <2y, fever in 3-8y and headache in >9y. An exhaustive description of objective and subjective symptoms by age is made. 18 patients were hospitalized, one with multisystem inflammatory syndrome in children. There were no deaths. Conclusions: Pediatric COVID-19 is a mild disease, with a large number of asymptomatic cases, with very few hospital admissions and deaths. The main setting for transmission is the household, and school closures should be a last resource measure during the COVID-19 pandemic. A specific clinical picture of pediatric COVID-19 was not found. (AU)

COVID-19 clinical features in primary care: COVIDPAP study.

OBJECTIVES: In Spain, the tools to diagnose COVID-19 were available in primary care from May 2020. Previously most studies described inpatients or patients in A&E departments, and fever and cough were the most frequent symptoms. This study aims to define the clinical picture of the pediatric COVID-19 in the community. METHODS: A descriptive and analytical observational study was performed including pediatric cases (0-14years) from 255 pediatricians, proportionally distributed to its population, from primary health centers in Spain, from 12th May 2020 to 30th April 2021. Diagnostics were made by PCR detection of viral RNA, rapid antigen detection test or positive IgG serology. RESULTS: There were 10,021 positive children included, 48.4% women, mean age 8,04±4.17years. Infection was detected due to contact tracing (70.9%), compatible symptoms (18.8%). Household was the main source of transmission (64.9%), followed by school setting (10%) or unknown (9.9%). We did not find any significant differences in the incidence between holidays and school terms. 43.2% of the children were asymptomatic. Most frequent symptoms are rhinorrhea in <2years, fever in 3-8years and headache in >9years. An exhaustive description of objective and subjective symptoms by age is made. 18 patients were hospitalized, one with multisystem inflammatory syndrome in children. There were no deaths. CONCLUSIONS: pediatric COVID-19 is a mild disease, with a large number of asymptomatic cases, with very few hospital admissions and deaths. The main setting for transmission is the household, and school closures should be a last resource measure during the COVID-19 pandemic. A specific clinical picture of pediatric COVID-19 was not found.

Publicaciones científicas de los pediatras españoles de Atención Primaria en los últimos seis años (2015-2020) / Scientific publications of primary care paediatricians in Spain the last six years (2015-2020)

Introducción: la actividad asistencial debería ir siempre ligada a una investigación de calidad, ya que mediante el método científico se analizan y estudian los problemas para buscar sus causas o soluciones, formando parte de un proceso de mejora continua de la asistencia clínica. El objetivo del presente estudio es conocer la frecuencia de participación de los pediatras de Atención Primaria (PAP) como autores de publicaciones de las principales revistas pediátricas nacionales e internacionales. Material y métodos: estudio descriptivo transversal. Se realizó una revisión de las autorías de los artículos publicados en todas las revistas pediátricas nacionales y regionales y en las tres revistas internacionales pediátricas de mayor relevancia, en el periodo de tiempo comprendido desde el 1 de enero de 2015 al 30 de junio de 2020. Resultados: se revisaron 6398 artículos, 2030 artículos de revistas nacionales y 4368 artículos de revistas internacionales. En los artículos de revistas nacionales, había un PAP entre los autores en 410 (20,2%), participaban exclusivamente PAP en 117 (5,8%) y el primer firmante era un PAP en 258 (12,7%). En los artículos de revistas internacionales, 31 (0,71%) contienen entre sus firmantes algún autor español y solo 5 cuentan con la participación de al menos un PAP. Conclusiones: la actividad investigadora y de publicaciones de ámbito nacional de los PAP es baja. A nivel internacional, hay pocas publicaciones de los pediatras españoles en las principales revistas pediátricas, siendo muy minoritaria la presencia de publicaciones de PAP en estas revistas (AU)

Introduction: health care delivery should always be associated with quality research, as the scientific method is used to assess and investigate problems to identify their causes or solutions as part of an ongoing health care quality improvement process. The objective of our study was to determine the frequency with which primary care paediatricians (PCPs) in Spain contribute as authors of publications in the main national and international paediatric journals.Material and methods: descriptive cross-sectional study. We reviewed the authorship of the articles published in every Spanish national and regional paediatric journal and in the 3 most relevant international paediatric journals in the period ranging from January 1, 2015 to June 30, 2020.Results: the review included a total of 6398 articles, 2030 from national journals and 4368 articles from international journals. In the group of articles published in Spanish journals, we found authors that were PCPs in 410 (20.2%), with exclusive participation of PCPs in 117 (5.8%) and a PCP listed as the first author in 258 (12.7%). In articles published in international journals, 31 (0.71%) had a Spanish author in the list, and only 5 listed at least one Spanish PCP.Conclusions: involvement in research and contribution to national scientific journals is low among PCPs. At the international level, there are few publications by Spanish paediatricians in the main paediatric journals, with an extremely low number of contributions by PCPs in these journals. (AU)

[COVID-19 clinical features in primary care: COVIDPAP study]. / Expresión clínica de la COVID-19 en pediatría de atención primaria: estudio COVIDPAP.

Objectives: In Spain, the tools to diagnose COVID-19 were available in primary care from May 2020. Previously most studies described inpatients, and fever and cough were the most frequent symptoms. This study aims to define the clinical picture of the pediatric COVID-19 in the community. Methods: A descriptive and analytical observational study was performed including pediatric cases (0-14y) from 255 pediatricians, proportionally distributed to its population, from primary health centers in Spain, from 12th May 2020 to 30th April 2021. Diagnostics were made by PCR detection of viral RNA, rapid antigen detection test or positive IgG serology. Results: There were 10,021 positive children included, 48.4% women, mean age 8,04 ± 4.17 years. Infection was detected due to contact tracing (70.9%), compatible symptoms (18.8%). Household was the main source of transmission (64.9%), followed by school setting (10%) or unknown (9.9%). We did not find any significant differences in the incidence between holidays and school terms. 43.2% of the children were asymptomatic. Most frequent symptoms are rhinorrhea in < 2 y, fever in 3-8 y and headache in > 9 y. An exhaustive description of objective and subjective symptoms by age is made. 18 patients were hospitalized, one with multisystem inflammatory syndrome in children. There were no deaths. Conclusions: Pediatric COVID-19 is a mild disease, with a large number of asymptomatic cases, with very few hospital admissions and deaths. The main setting for transmission is the household, and school closures should be a last resource measure during the COVID-19 pandemic. A specific clinical picture of pediatric COVID-19 was not found.