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Male breast cancer (MBC) is a rare condition, accounting for approximately 1 % of all breast cancer cases. Nevertheless, the paucity of MBC-specific research has impeded a thorough understanding of MBC. In this study, we aimed to delineate the epidemiological implications of MBC in Brazil and benchmarked it against female breast cancer (FBC). This retrospective study analyzed data from the DATASUS database (2017–2021), which assessed the incidence of breast cancer in both sexes. All statistical analyses were performed using descriptive statistics and inferential methods, with significance set at a 95 % confidence interval. We identified 4,326 (1.7 %) and 233,793 (94.2 %) patients with MBC and FBC, respectively, in Brazil. Despite the general population concentration in the Southeast, MBC cases were more prevalent in the Northeast (p

Malignant Brenner tumor (MBT) of the ovary is exceedingly rare, and studies of MBT have been limited to case reports and small case series. MBT shares similar clinical and radiological presentations with other ovarian epithelial malignancies, and the diagnosis of MBT is predominantly based on histopathologic evaluation. Recently, relatively large retrospective studies have advanced understanding of their histogenesis and malignant transformation, as well as on the clinical management of this rare subtype of ovarian carcinoma. In this article, we review the published English literature on MBT, with an emphasis on the histopathologic evaluation, molecular biology, and clinical management of MBT.

Objectives: To determine if shorter courses of antibiotic therapy for group A Streptococcus (GAS) bacteremia are associated with excess mortality. Methods: In this retrospective study of consecutive cases of GAS bacteremia in tropical Australia, the duration of antibiotic therapy was correlated with 90-day all-cause mortality. Results: There were 286 episodes of GAS bacteremia; the patients’ median (interquartile range) age was 60 (48-71) years and 169/286 (59.1%) patients identified as an Indigenous Australian. There were 227/286 (79.4%) patients with a significant comorbidity. The all-cause 90-day mortality was 16/286 (5.6%); however, 12/16 (81.3%) patients died while still receiving their initial course of antibiotics and only 7/16 (43.8%) deaths were directly attributable to the GAS infection. After excluding patients who died while taking their initial course of antibiotics and those in whom the duration of therapy was uncertain, there was no difference in 90-day mortality between patients receiving ≤5 days of intravenous antibiotics and those receiving longer courses (1/137 [0.7%] vs 3/107 [2.8%], P-value = 0.32) nor in patients receiving ≤10 days of total therapy and those receiving longer courses (1/67 [1.5%] vs 3/178 [1.7%], P-value = 1.0). Conclusion: Even among patients with significant comorbidity, shorter antibiotic courses for GAS bacteremia are not associated with excess mortality.

Resumen: Introducción: Las reclamaciones constituyen una de las principales fuentes de información para evaluar la calidad percibida en los centros asistenciales, siendo la cirugía ortopédica y traumatología (COT) una de las especialidades con mayor probabilidad de recibirlas por su elevada demanda quirúrgica que genera importantes listas de espera. Objetivos: Mostrar la evolución de las reclamaciones presentadas en un servicio de COT, clasificar los motivos expuestos e identificar las oportunidades de mejora derivadas de las mismas. Metodología: Estudio epidemiológico descriptivo, observacional y de orientación temporal retrospectiva. Revisión de los registros correspondientes a las reclamaciones presentadas durante el periodo 2014-2018 en el servicio de COT de un hospital universitario. Para la clasificación de las reclamaciones se han utilizado los motivos establecidos por la aseguradora pública CatSalut. El análisis estadístico se ha realizado mediante el programa Excel® y el software R-Project (versión 4.0.2), considerándose un nivel de significación estadística de p

Objective: To define the microbiologic characteristics of animal bites in tropical Australia and the appropriateness of current Australian antimicrobial guidelines for their management. Methods: This retrospective audit examined hospitalizations in tropical Australia after an animal bite or animal-associated penetrating injury between 2013 and 2020. The primary outcome was a composite of death, intensive care unit admission, amputation, quaternary center transfer, or unplanned rehospitalization. Results: A wide variety of animals were implicated, but snakes (734/1745, 42%), dogs (508/1745, 29%), and cats (153/1745, 9%) were the most common. Hospital presentation after 24 hours (odds ratio (OR) (95% confidence interval (CI)): 68.67 (42.10-112.01)) and a cat-related injury (OR (95% CI): 22.20 (11.18-44.08)) were independently associated with an increased risk of infection. A pathogen not covered by the relevant antimicrobial regimen recommended in Australian guidelines was identified in only 12/1745 (0.7%) cases. The primary outcome occurred in 107/1745 (6%) and was independently associated with tissue trauma (OR (95% CI): 9.29 (6.05-14.25), p

Purpose: Exome sequencing (ES) is a powerful tool that facilitates the diagnosis of patients with rare Mendelian syndromes. In 2018 the Israeli Ministry of Health initiated a national pilot program that funds ES for outpatients with global developmental delay (GDD). Here, we describe the 3-year impact of this program on patient care in a single tertiary hospital. Methods: From 2018 to 2020, trio ES was performed on 170 participants fulfilling Israeli Ministry of Health criteria: (1) moderate to severe GDD and (2) mild GDD with epilepsy or a major congenital anomaly. We retrospectively analyzed this cohort. Results: A diagnosis was achieved in 74 individuals (43%). There were 82 clinically significant variants, the majority being novel. Consanguinity was reported in 22% and was not associated with a higher diagnostic rate. The presence of autism spectrum was associated with a lower diagnostic rate of 8/33 (24%). Autosomal dominant inheritance was identified in 14% of participants, and the parental phenotype ranged between fully affected and asymptomatic. Among the diagnosed participants, 16% had an unexpected diagnosis that did not fit the typical clinical presentation. In 9%, the diagnosis changed short-term active clinical management, in 19%, the surveillance recommendations, and in 23%, the family-focused outcomes. Conclusion: The introduction of a national program that funds ES for GDD has transformed patient care, leading to a significant effect on medical management and treatment. The high rate of an unexpected inheritance mode and variable phenotypes emphasizes the diagnostic complexity of neurodevelopmental disorders and the strength of a non-targeted approach.

Introduction: Traumatic brain injury in the elderly population can have a substantial impact on patients’ quality of life. In this regard, successful treatment strategies are hard to define to date. Research question: In order to facilitate further insight, this study assessed outcomes following acute subdural hematoma evacuation in patients aged ≥65 years in a large patient series. Material and methods: A manual screening of the clinical records of 2999 TBI patients aged ≥65 years, admitted to the University Hospital Leuven (Belgium) between 1999 and 2019, was performed. Results: A total of 149 patients were identified with aSDH, of whom 32 underwent early surgery, 33 underwent delayed surgery and 84 were treated conservatively. Patients who underwent early surgery had the lowest median GCS, poorest Marshall CT scores, longest hospital and ICU stay, and highest intensive care unit admission and redo surgery rates. 30-d mortality was 21.9% in patients undergoing early surgery, 3.0% in patients undergoing late surgery and 16.7% in patients who were treated conservatively. Discussion and conclusion: In conclusion, patients in whom surgery could not be delayed had the worst presentation and poorest outcomes as opposed in patients in whom delay was possible. Surprisingly, patients treated conservatively had worse outcomes than those treated with delayed surgery. These results might indicate that if the GCS at admission is still adequate, an initial strategy of waiting and seeing might be associated with better outcomes. Future prospective studies with sufficient sample size are warranted to draw more definitive conclusions on the value of early vs. late surgery in elderly patients with aSDH.

Acalabrutinib, a second-generation Bruton's tyrosine kinase inhibitor (BTKi), offers an improved safety profile compared to first-generation inhibitors like ibrutinib. While BTKi guidelines exist, practical differences between BTKis-such as drug interactions and tolerance-are not fully addressed. Therefore, a consensus on acalabrutinib use would benefit the medical community. This 2-round Delphi study involved hematologists, pharmacists, cardiologists, dermatologists, and nurse practitioners throughout France to establish consensus-based practical guidance on managing adverse events (AEs) associated with acalabrutinib in chronic lymphocytic leukemia. Key findings highlighted the need for a hospital pharmacist to analyze drug interactions before starting acalabrutinib. Additionally, the experts' opinion was to avoid the concomitant use of acalabrutinib with strong CYP3A inhibitors due to an increased risk of toxicity and with strong CYP3A inducers due to potential efficacy concerns. Importantly, our study did not find contraindications for acalabrutinib in patients with current or previous atrial fibrillation. The panel emphasized the importance of measuring blood pressure at every clinical visit for patients treated with acalabrutinib and opposed the initiation of acalabrutinib in patients on both aspirin and clopidogrel. For invasive dermatological or dental procedures, acalabrutinib should be discontinued 4 days prior and resumed 48 hours postprocedure in the absence of bleeding. Additionally, patients should be informed about the risk of headaches, particularly during the first month of treatment, and paracetamol use in combination with caffeine is recommended for managing grade ≥ 2 headaches under acalabrutinib treatment. This Delphi study underscored the effectiveness of a collaborative process in enhancing the management of acalabrutinib-associated AEs., Competing Interests: Disclosure LY received consulting fees from AbbVie, AstraZeneca, BeiGene, BMS/Celgene, Gilead/Kite, Janssen, and Roche. SE received consultancy fees from Amgen, AstraZeneca, Bayer, BMS, Eisai, Leo Pharma, and Pierre Fabre. VL received honoraria from AbbVie, AstraZeneca, and BeiGene. VS received consulting fees from Novartis, BMS, MSD, Pierre Fabre, AstraZeneca, Janssen, Bayer, and Immunocore. CT received consulting fees from AbbVie, AstraZeneca, Beigene, and Janssen. The other authors do not report any conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Molar incisor hypomineralization (MIH) is defined as hypomineralization of systemic origin of one to four first permanent molars, and incisors are also frequently affected. This disorder is a serious concern in pediatric dentistry. Teeth affected by MIH have many dental problems, such as hypersensitivity, poor aesthetics, and rapid progression of dental caries. The prevalence of MIH ranges from 2.8% to 21% among studies with more than 1000 subjects in different countries and age groups. The etiology of MIH is unclear, but genetic and environmental factors have been proposed. This review describes the prevalence, etiology, and clinical management of MIH. A detailed description of MIH prevalence in Japan is also provided.

Background: Myoid Hamartoma of the breast (MHB) is an extremely rare benign breast lesion composed of mammary ducts and lobules, fibrous stroma, adipose tissue, and smooth muscle. Due to its rarity, the clinical management of MHB is not well described. Surgical excision is the most common form of management. This study reviews the current literature on the clinical management of MHB and describes a case report of a young patient presenting with MHB managed with surveillance and shared-decision making. Materials and methods: A healthy 23-year-old female presented with a one-year history of a palpable left breast mass. Her right breast exam was normal. Ultrasound of the left breast revealed a 2.7 cm × 1.4 cm × 2.4 cm lobulated mass at the one o'clock position. The mass caused slight discomfort to palpation but otherwise had no associated skin changes. Ultrasound-guided biopsy revealed a left breast myoid hamartoma. Management options were presented to the patient, and she elected to observe the mass with surveillance imaging. Results: There have been no reported cases in the literature of malignant transformation of MHB. Rather than rely on reflexive surgical excision of MHB, our review suggests that surveillance and routine imaging may be an appropriate form of clinical management in patients who present with a favorable clinical and histopathological profile which includes: a low MIB-1 proliferative index, low breast cancer risk assessment score, lesion size less than 1.2 cm, and radiological-pathological concordance. Conclusion: Further research is needed to determine the clinical significance and threshold levels of these clinical and histopathological factors in patient care. However, given current trends to minimize over treatment in breast pathology, we pose that observation of MHB can be performed when favorable clinical criteria is met.

Context: A congenital solitary functioning kidney (cSFK) is a common developmental defect that predisposes to hypertension and chronic kidney disease (CKD) as a consequence of hyperfiltration. Every urologist takes care of patients with a cSFK, since some will need lifelong urological care or will come with clinical problems or questions to an adult urologist later in life. Objective: We aim to provide clear recommendations for the initial clinical management and follow-up of children with a cSFK. Evidence acquisition: PubMed and EMBASE were searched to identify relevant publications, which were combined with guidelines on related topics and expert opinion. Evidence synthesis: Initially, cSFK diagnosis should be confirmed and risk factors for kidney injury should be identified using ultrasound. Although more research into early predictors of kidney injury is needed, additional congenital anomalies of the kidney or urinary tract and absence of compensatory kidney hypertrophy have repeatedly been associated with a worse prognosis. The role of voiding cystourethrography and antibiotic prophylaxis remains controversial, and is complicated by the exclusion of children with a cSFK from studies. A yearly follow-up for signs of kidney injury is recommended for children with a cSFK. As masked hypertension is prevalent, annual ambulatory blood pressure measurement should be considered. During puberty, an increasing incidence of kidney injury is seen, indicating that long-term follow-up is necessary. If signs of kidney injury are present, angiotensin converting enzyme inhibitors are the first-line drugs of choice. Conclusions: This overview points to the urological and medical clinical aspects and long-term care guidance for children with a cSFK, who are at risk of hypertension and CKD. Monitoring for signs of kidney injury is therefore recommended throughout life. Large, prospective studies with long-term follow-up of clearly defined cohorts are still needed to facilitate more risk-based and individualized clinical management. Patient summary: Many children are born with only one functioning kidney, which could lead to kidney injury later in life. Therefore, a kidney ultrasound is made soon after birth, and other investigations may be needed as well. Urologists taking care of patients with a solitary functioning kidney should realize the long-term clinical aspects, which might need medical management.

This review presents a conceptual framework and supporting evidence that links impaired motor control after sport-related concussion (SRC) to increased risk for musculoskeletal injury. Multiple studies have found that athletes who are post-SRC have higher risk for musculoskeletal injury compared to their counterparts. A small body of research suggests that impairments in motor control are associated with musculoskeletal injury risk. Motor control involves the perception and processing of sensory information and subsequent coordination of motor output within the central nervous system to perform a motor task. Motor control is inclusive of motor planning and motor learning. If sensory information is not accurately perceived or there is interference with sensory information processing and cognition, motor function will be altered, and an athlete may become vulnerable to injury during sport participation. Athletes with SRC show neuroanatomic and neurophysiological changes relevant to motor control even after meeting return to sport criteria, including a normal neurological examination, resolution of symptoms, and return to baseline function on traditional concussion testing. In conjunction, altered motor function is demonstrated after SRC in muscle activation and force production, movement patterns, balance/postural stability, and motor task performance, especially performance of a motor task paired with a cognitive task (i.e., dual-task condition). The clinical implications of this conceptual framework include a need to intentionally address motor control impairments after SRC to mitigate musculoskeletal injury risk and to monitor motor control as the athlete progresses through the return to sport continuum.

Objectives: To determine the comparative prognostic utility of commonly used disease prediction scores in adults with presumed community-acquired sepsis in a resource-limited tropical setting. Methods: This prospective, observational study was performed on the medical ward of a tertiary-referral hospital in Yangon, Myanmar. The ability of the National Early Warning Score 2 (NEWS2), quick NEWS (qNEWS), quick Sequential Organ Failure Assessment (qSOFA) score, Universal Vital Assessment (UVA) and Sequential Organ Failure Assessment (SOFA) scores to predict a complicated inpatient course (death or requirement for intensive care unit (ICU) support) in patients with two or more systemic inflammatory response syndrome criteria was determined. Results: Among the 509 patients, 30 (6%) were HIV-seropositive. The most commonly confirmed diagnoses were tuberculosis (30/509, 5.9%) and measles (26/509, 5.1%). Overall, 75/509 (14.7%) died or required ICU support. All the scores except the qSOFA score, which was inferior, had a similar ability to predict a complicated inpatient course. Conclusions: In this resource-limited tropical setting, disease severity scores calculated at presentation using only vital signs–such as the NEWS2 score–identified high-risk sepsis patient as well as the SOFA score, which is calculated at 24 h and which also requires laboratory data. Use of these simple clinical scores can be used to facilitate recognition of the high-risk patient and to optimise the use of finite resources.

Background: Children with severe falciparum malaria in malaria-endemic regions are predisposed to developing life-threatening bacterial co-infection. International guidelines therefore recommend empirical broad-spectrum antibacterial therapy in these children. Few studies have examined co-infection in adults, although it has been believed to be relatively rare; antibacterial therapy is therefore not routinely recommended in adults with falciparum malaria. Discussion: However, the fundamental pathophysiology of falciparum malaria in adults and children is the same; it is therefore unclear why adults would not also be predisposed to bacterial infection. Indeed, recent studies have identified bacteraemia in >10% of adults hospitalized with malaria. Some have suggested that these adults probably had bacterial sepsis, with the parasitaemia an incidental finding. However, it is usually impossible in resource-limited settings to determine–at presentation–whether critically ill, parasitaemic adults have severe malaria, bacterial sepsis, or both. Given the significant case-fatality rates of severe malaria and bacterial sepsis, the pragmatic initial approach would be to cover both possibilities. Conclusions: Life-threatening bacterial co-infection may be more common in critically ill adults with malaria than previously believed. While further prospective data are awaited to confirm these findings, it might be more appropriate to provide empirical aantibacterial cover in these patients than current guidelines suggest.

Introduction: Clinicians are commonly taught that if patients with suspected rickettsial disease have continuing fever after 48 hours of anti-rickettsial therapy, an alternative diagnosis is likely. Methods: This retrospective study of patients hospitalised with scrub typhus and Queensland tick typhus (QTT) in tropical Australia, examined the time to defervescence after initiation of the patients’ anti-rickettsial therapy. It also identified factors associated with delayed defervescence (time to defervescence >48 hours after antibiotic commencement). Results: Of the 58 patients, 32 (56%) had delayed defervescence. The median (interquartile range (IQR)) age of patients with delayed defervescence was 52 (37-62) versus 40 (28-53) years in those who defervesced within 48 hours (p = 0.05). Patients with delayed defervescence were more likely to require Intensive Care Unit (ICU) admission than those who defervesced within 48 hours (12/32 (38%) versus 3/26 (12%), p = 0.02). Even among patients not requiring ICU care, patients with delayed defervescence required a longer hospitalisation than that those who defervesced within 48 hours (median (IQR): 6 (3-8) versus 3 (2-5) days, p = 0.006). Conclusions: A significant proportion of patients with confirmed scrub typhus and QTT will remain febrile for >48 hours after appropriate anti-rickettsial therapy. Delayed defervescence is more common in patients with severe disease.

The novel coronavirus disease 2019 (COVID-19) is one of the biggest public health crises globally. Although Africa did not display the worst-case scenario compared to other continents, fears were still at its peak since Africa was already suffering from a heavy load of other life-threatening infectious diseases such as HIV/AIDS and malaria. Other factors that were anticipated to complicate Africa's outcomes include the lack of resources for diagnosis and contact tracing along with the low capacity of specialized management facilities per capita. The current review aims at assessing and generating discussions on the realities, and pros and cons of the WHO COVID-19 interim guidance 2020.5 considering the known peculiarities of the African continent. A comprehensive evaluation was done for COVID-19-related data published across PubMed and Google Scholar (date of the last search: August 17, 2020) with emphasis on clinical management and psychosocial aspects. Predefined filters were then applied in data screening as detailed in the methods. Specifically, we interrogated the WHO 2020.5 guideline viz-a-viz health priority and health financing in Africa, COVID-19 case contact tracing and risk assessment, clinical management of COVID-19 cases as well as strategies for tackling stigmatization and psychosocial challenges encountered by COVID-19 survivors. The outcomes of this work provide links between these vital sub-themes which may impact the containment and management of COVID-19 cases in Africa in the long-term. The chief recommendation of the current study is the necessity of prudent filtration of the global findings along with regional modelling of the global care guidelines for acting properly in response to this health threat on the regional level without exposing our populations to further unnecessary adversities.

Background: There are limited data to guide the diagnosis and management of vasa previa. Currently, what is known is largely based on case reports or series and cohort studies., Objective: This study aimed to systematically collect and classify expert opinions and achieve consensus on the diagnosis and clinical management of vasa previa using focus group discussions and a Delphi technique., Study Design: A 4-round focus group discussion and a 3-round Delphi survey of an international panel of experts on vasa previa were conducted. Experts were selected on the basis of their publication record on vasa previa. First, we convened a focus group discussion panel of 20 experts and agreed on which issues were unresolved in the diagnosis and management of vasa previa. A 3-round anonymous electronic survey was then sent to the full expert panel. Survey questions were presented on the diagnosis and management of vasa previa, which the experts were asked to rate on a 5-point Likert scale (from "strongly disagree"=1 to "strongly agree"=5). Consensus was defined as a median score of 5. Following responses to each round, any statements that had median scores of ≤3 were deemed to have had no consensus and were excluded. Statements with a median score of 4 were revised and re-presented to the experts in the next round. Consensus and nonconsensus statements were then aggregated., Results: A total of 68 international experts were invited to participate in the study, of which 57 participated. Experts were from 13 countries on 5 continents and have contributed to >80% of published cohort studies on vasa previa, as well as national and international society guidelines. Completion rates were 84%, 93%, and 91% for the first, second, and third rounds, respectively, and 71% completed all 3 rounds. The panel reached a consensus on 26 statements regarding the diagnosis and key points of management of vasa previa, including the following: (1) although there is no agreement on the distance between the fetal vessels and the cervical internal os to define vasa previa, the definition should not be limited to a 2-cm distance; (2) all pregnancies should be screened for vasa previa with routine examination for placental cord insertion and a color Doppler sweep of the region over the cervix at the second-trimester anatomy scan; (3) when a low-lying placenta or placenta previa is found in the second trimester, a transvaginal ultrasound with Doppler should be performed at approximately 32 weeks to rule out vasa previa; (4) outpatient management of asymptomatic patients without risk factors for preterm birth is reasonable; (5) asymptomatic patients with vasa previa should be delivered by scheduled cesarean delivery between 35 and 37 weeks of gestation; and (6) there was no agreement on routine hospitalization, avoidance of intercourse, or use of 3-dimensional ultrasound for diagnosis of vasa previa., Conclusion: Through focus group discussion and a Delphi process, an international expert panel reached consensus on the definition, screening, clinical management, and timing of delivery in vasa previa, which could inform the development of new clinical guidelines., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Summary: Obesity-related osteoarthritis (OA) is a complex, multifactorial condition that can cause significant impact on patients’ quality of life. Whilst chronic inflammation, adipocytokines and metabolic factors are considered to be important pathogenic factors in obesity related OA, there has been limited investigation into the biomechanical impact of obesity on OA development. This review aims to demonstrate that mechanical factors are the major pathological cause of obesity-related OA. The effect of obesity on pathological changes to the osteochondral unit and surrounding connective tissues in OA is summarized, as well as the impact of obesity-related excessive and abnormal joint loading, concomitant joint malalignment and muscle weakness. An integrated therapeutic strategy based on this multi-factorial presentation is presented, to assist in the management of obesity related OA. The translational potential of this article: Despite the high prevalence of obesity-related OA, there is no specific guideline available for obesity-related OA management. In this review, we demonstrated the pathological changes of obesity-related OA and summarized the impact of biomechanical factors by proposing a hypothetical model of obesity-related OA change. Therapeutic strategies based on adjusting abnormal mechanical effects are presented to assist in the management of obesity-related OA.

Resumen: Objetivo: Caracterizar la situación actual del médico gestor de la demanda (MGD) en la atención primaria de salud (APS), desde las percepciones de aquellos que cumplen ese rol, sus pares médicos y los directivos de los centros de salud familiar (CESFAM). Diseño: Estudio transversal cualitativo con enfoque de teoría fundamentada. Emplazamiento: Cuatro CESFAM del Servicio de Salud Metropolitano Sur Oriente en Santiago, Chile. Participantes: Médico gestor de la demanda, médicos generales y directores de CESFAM. Método: Se utilizó la entrevista semiestructurada y el grupo de discusión como técnica de recolección de datos. Se realizó codificación abierta, axial y selectiva con el apoyo del software NVivo v.12. Resultados: El MGD realiza en la práctica más funciones que las definidas para el cargo por el Ministerio de Salud, generando una sensación de falta de tiempo para realizar su labor, lo que representa su principal barrera en el trabajo y refleja la falta de apoyo institucional que reciben de sus jefaturas. Entre estas funciones invisibles están: retroalimentar al equipo médico, liderar reuniones clínicas y generar protocolos de referencia. Para el buen desempeño del MGD es necesario contar con competencias técnicas y ser reconocido por sus pares. Se estimó que el médico de familia es el profesional más apto para el cargo. La labor del MGD está limitada por factores institucionales como las listas de espera, la falta de especialistas y la baja coordinación entre niveles asistenciales. Conclusiones: Estandarizar las funciones del MGD es un elemento necesario para su consolidación y lograr cumplir los objetivos de mantener la continuidad del cuidado en la población. Abstract: Objective: Characterize the current situation of the demand manager physician (DMP) in primary health care (PHC), from the perceptions of those who fulfill this role, their medical peers and the directors of the family health centers (CESFAMs). Design: Qualitative cross-sectional study with a grounded theory approach. Site: Four CESFAMs from the South East Metropolitan Health Service in Santiago, Chile. Participants: Demand manager physician, general practitioners and directors of CESFAM. Method: A semi-structured interview and discussion group were used as data collection technique. Open, axial, and selective coding was carried out with the support of the NVivo12 software. Results: In practice, DMP performs more functions than those defined for the position by the Ministry of Health, generating the feeling of lack of time to carry out their work, what represents their main barrier at work and reflects the absence of institutional support they receive from their employees. Among these invisible functions are: providing feedback to the medical team, leading clinical meetings, and generating reference protocols. For the good performance of the DMP it is necessary to have technical skills and be recognized by their peers. It was estimated that the family doctor is the most suitable professional for the position. The work of the DMP is limited by institutional factors such as waiting lists, lack of specialists, and poor coordination between levels of care. Conclusions: Standardizing the functions of the DMP is a necessary element for its consolidation and achieving the objectives of maintaining continuity of care in the population.

Study objective: Transthoracic echocardiograms (TTE) are perceived to be overused and multiple TTEs are often ordered within one inpatient visit with unclear utility. This study identified inpatients who received multiple TTEs to determine the appropriateness, results, and subsequent management of repeat TTEs. Design: Retrospective Cohort Study. Setting: Single academic medical center. Participants: Subjects over age 18 who underwent >1 TTE during hospitalization in 2020. Interventions: N/A Main outcome measures: Appropriateness of TTE, TTE results, subsequent changes in management. Results: Of the 875 subjects, the average age was 60 years old with a male predominance (57.8%). In comparing the first and second TTE results, the frequency of new abnormal findings decreased significantly from 44.7% to 15.1% (p

The aim of this retrospective observational study was to introduce a comprehensive MRI evaluation criterion for the clinical management of synovial chondromatosis of the temporomandibular joint (TMJ-SC). Patients received different treatments according to the MRI evaluation system: bone erosion, extent, articular disc condition, location, maturity, and size of loose body. At least a 2-year follow-up was completed to assess tumor recurrence, visual analogue scale score for pain (VAS) and maximum interincisal opening (MIO). Of the 195 patients included for TMJ-SC, 34 received arthroscopy and 161 received open surgery. Among the patients with significant extent of SC, 32 received temporary resection of the condylar neck or zygomatic arch and 2 received treatment combined with ear, nose and throat(ENT). 28 received articular disc reconstruction and 56 received disc repositioning. Patients showed good recovery of joint function with only two cases of tumor recurrence at an average follow-up of 75.1 months after surgery. The MIO had improved from 30.2 mm to 40.0 mm(P < 0.0001) and VAS had decreased from 5.1 to 0.78(P < 0.0001).The preoperative MRI evaluation principles has been effective in selecting appropriate surgical options., Competing Interests: Declaration of competing interest None, (Copyright © 2024. Published by Elsevier Ltd.)

Melioidosis is a life-threatening, emerging infectious disease caused by the environmental bacterium Burkholderia pseudomallei. Melioidosis is hyperendemic in tropical Australia and southeast Asia, however the disease is increasingly encountered beyond these regions. Early diagnosis is essential as the infection has a case-fatality rate of up to 50 %. Melioidosis most commonly involves the lungs, although almost any organ can be affected. Most patients present acutely but an insidious presentation over weeks to months is also well described. We present a case series of 7 patients from tropical Australia whom local clinicians initially believed to have cancer ‒ most commonly lung cancer ‒ only for further investigation to establish a diagnosis of melioidosis. All 7 patients had comorbidities that predisposed them to developing melioidosis and all survived, but their delayed diagnosis resulted in 3 receiving anti-cancer therapies that resulted in significant morbidity. The study emphasises the importance of thorough diagnostic evaluation and repeated collection of microbiological samples. It is hoped that our experience will encourage other clinicians ‒ in the appropriate clinical context ‒ to consider melioidosis as a potential explanation for a patient's presentation, expediting its diagnosis and the initiation of potentially life-saving therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: In recent years, active surveillance has been introduced as an alternative to excisional treatment in younger women with cervical intraepithelial neoplasia grade 2 because regression rates are high and excisional treatment is associated with increased risk of preterm birth. However, early identification of women at increased risk of persistence/progression is important to ensure timely treatment. Evidence is limited on biomarkers that may be used to identify women at increased risk of persistence/progression., Objective: This study aimed to describe human papillomavirus HPV type-specific persistence/progression in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2., Study Design: We conducted a historical cohort study of women aged 23 to 40 years diagnosed with cervical intraepithelial neoplasia grade 2 at Aarhus University Hospital from 2000 to 2010. Women were identified through the Danish Pathology Data Bank (DPDB) and were considered as undergoing active surveillance if they had a first record of a cervical biopsy within 2 years after index diagnosis and no loop electrosurgical excision procedure before this. Human papillomavirus genotyping was performed on archived tissue samples using the HPV SPF 10 -DEIA-LiPA 25 system (DNA ELISA [enzyme-linked immunosorbent assay] HPV SPF10 kit and RHA HPV SPF10-LiPA25 kit). Persistence/progression was defined as having a record of cervical intraepithelial neoplasia grade ≥2 in the DPDB determined on the last and worst diagnosis on a biopsy or loop electrosurgical excision procedure specimen during follow-up. We estimated the relative risk (95% confidence interval) of persistence/progression using a modified Poisson model., Results: A total of 455 women were included. Two-thirds were aged ≤30 years (73.8%) at index diagnosis, and nearly half had a high-grade index cytology (48.8%). Overall, 52.2% of all women had cervical intraepithelial neoplasia grade ≥2 during follow-up; 70.5% were human papillomavirus-16-positive and 29.5% were positive for other human papillomavirus types. Human papillomavirus-16 was associated with a significantly higher risk of persistence/progression (relative risk, 1.64; 95% confidence interval, 1.37-1.95) compared with non-human papillomavirus-16. The risk of persistence/progression was highest in human papillomavirus-16-positive women with a high-grade index cytology compared with human papillomavirus-16-positive women with a low-grade cytology (relative risk, 1.29; 95% confidence interval, 1.03-1.61), whereas no differences were observed across age groups., Conclusion: The highest risk of persistence/progression was observed among human papillomavirus-16-positive women, particularly those with associated high-grade cytology. These findings suggest that early excisional treatment should be considered in this group of women., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

In the realm of cardiovascular health, isolated left ventricular noncompaction (LVNC) stands out for its distinct morphological features and the clinical challenges it presents, particularly in adults. This literature review explores the intricacies of LVNC, aiming to unravel its epidemiological spread, diagnostic hurdles, and therapeutic strategies. Despite technological advancements in cardiac imaging that have improved the recognition of LVNC, a significant gap persists alongside a fragmented understanding of its pathogenesis. The studies scrutinized reveal a broad spectrum of prevalence rates influenced by diverse diagnostic tools and demographic variables. This variation underscores the complexity of accurately identifying LVNC and the resultant implications for clinical management. The review succinctly addresses the need for precise guidelines to navigate the diagnosis of LVNC and outlines the imperative for tailored clinical management approaches that cater to the wide array of patient presentations, from asymptomatic cases to those with severe cardiac dysfunction. By highlighting the critical gaps in current literature-namely the absence of standardized diagnostic criteria and a comprehensive pathogenic model-the review sets the stage for future research directions. These endeavors are essential for enhancing diagnostic accuracy, refining management protocols, and ultimately improving patient outcomes in this complex subset of cardiomyopathy, thus contributing significantly to the advancement of cardiovascular medicine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Coronary artery calcium scoring (CACS) improves management of chest pain patients. However, it is unknown whether the benefit of CACS is dependent on the clinical likelihood (CL)., Objectives: This study aims to investigate for which patients CACS has the greatest benefit when added to a CL model., Methods: Based on data from a clinical database, the CL of obstructive coronary artery disease (CAD) was calculated for 39,837 patients referred for cardiac imaging due to symptoms suggestive of obstructive CAD. Patients were categorized according to the risk factor-weighted (RF-CL) model (very low, ≤5%; low, >5 to ≤15%; moderate >15 to ≤50%; high, >50%). CL was then recalculated incorporating the CACS result (CACS-CL). Reclassification rates and the number needed to test with CACS to reclassify patients were calculated and validated in 3 independent cohorts (n = 9,635)., Results: In total, 15,358 (39%) patients were down- or upclassified after including CACS. Reclassification rates were 8%, 75%, 53%, and 30% in the very low, low, moderate, and high RF-CL categories, respectively. Reclassification to very low CACS-CL occurred in 48% of reclassified patients. The number needed to test to reclassify 1 patient from low RF-CL to very low CACS-CL was 2.1 with consistency across age, sex, and cohorts. CACS-CL correlated better to obstructive CAD prevalence than RF-CL., Conclusions: Added to an RF-CL model for obstructive CAD, CACS identifies more patients unlikely to benefit from further testing. The number needed to test with CACS to reclassify patients depends on the pretest RF-CL and is lowest in patients with low (>5% to ≤15%) likelihood of CAD., Competing Interests: Funding Support and Author Disclosures Drs Newby and Williams have received support from the British Heart Foundation (FS/ICRF/20/26002, CH/09/002, RG/16/10/32375, RE/18/5/34216). The PROMISE study was supported by grants from the National Heart, Lung, and Blood Institute (R01HL098237, R01HL098236, R01HL098305, and R01HL098235). Dr Winther has received support from the Novo Nordisk Foundation Clinical Emerging Investigator grant (NNF21OC0066981). Dr Williams has been a speaker for Canon Medical Systems, Siemens Healthineers, and Novartis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The risk of developing new-onset arrhythmia or exacerbation of a pre-existing arrhythmia is increased during pregnancy because of profound physiological and hormonal changes. The incidence of arrhythmias in pregnancy is not well-reported and especially data on ventricular arrhythmia are scarce. Arrhythmia during pregnancy is associated with adverse maternal and fetal outcomes and the optimization of clinical management is hindered by a paucity of evidence, as guidelines are either based on studies in the general population or on case series in pregnancy. In any case, optimal care for these patients includes a multidisciplinary approach, integrating the different considerations in maternal cardiac, obstetric and fetal health. In this manuscript we present three cases of ventricular arrhythmia during pregnancy and describe our considerations in clinical decision-making with regard to diagnostic challenges and treatment choices.

The spread of the emerging pathogen, named as SARS-CoV-2, has led to an unprecedented COVID-19 pandemic since 1918 influenza pandemic. This review first sheds light on the similarity on global transmission, surges of pandemics, and the disparity of prevention between two pandemics. Such a brief comparison also provides an insight into the potential sequelae of COVID-19 based on the inference drawn from the fact that a cascade of successive influenza pandemic occurred after 1918 and also the previous experience on the epidemic of SARS and MERS occurring in 2003 and 2015, respectively. We then propose a systematic framework for elucidating emerging infectious disease (EID) such as COVID-19 with a panorama viewpoint from natural infection and disease process, public health interventions (non-pharmaceutical interventions (NPIs) and vaccine), clinical treatments and therapies (antivirals), until global aspects of health and economic loss, and economic evaluation of interventions with emphasis on mass vaccination. This review not only concisely delves for evidence-based scientific literatures from the origin of outbreak, the spread of SARS-CoV-2 to three surges of pandemic, and NPIs and vaccine uptakes but also provides a new insight into how to apply big data analytics to identify unprecedented discoveries through COVID-19 pandemic scenario embracing from biomedical to economic viewpoints.

The COVID-19 pandemic has now risen to a global health crisis across the globe. This novel virus outbreak has challenged India’s economic, medical and public health infrastructure. Health care professionals and researchers around the world are looking for an effective treatment regime for COVID-19. The number of people infected by COVID-19 in India crossed 9.74 million; nearly eleven - months after the country reported its first case. The Ministry of Health and Family Welfare of India (MOHFW) has taken numerous measures to raise awareness on COVID-19 and the necessary actions to control the spread of the virus. The central and state governments are formulating several wartime protocols to achieve this goal. The MOHFW has implemented the new clinical management protocol to treat COVID-19. Besides, the Ministry of AYUSH has also provided guidelines to use conventional preventive and treatment strategies to enhance immunity. The national recovery rate has increased to 94.66% and the reported fatality rate is down to 1.45, due to “test, track and treat”. MOHFW and Ministry of AYUSH are the two pillars of health care to prevent and manage the current pandemic outbreak in India. Since, there is no specific drug or vaccine effective against COVID-19 infection, exploring every possible option for prevention and treatment is of great importance.

Despite the recent developments in the diagnosis and management of inflammatory bowel diseases (IBD), patients still suffer from disabling bowel symptoms and significant disease complications and many questions remain to improve their care. IBD is a chronic disease, whose management could be divided into the five different stages of chronic diseases, ranging from the pre-treatment evaluation phase to the induction therapy, maintenance therapy, monitor and re-establishment of control and the cessation of the disease. Reconciling these phases with the current unmet needs in IBD could help tailor priorities for research. In this review, some of the unanswered questions in the management of both Crohn’s Disease and Ulcerative Colitis will be addressed, by following this paradigm of chronic diseases’ management.

Angiosarcoma (AS) represents a rare and aggressive vascular sarcoma, posing distinct challenges in clinical management compared to other sarcomas. While the current European Society of Medical Oncology (ESMO) clinical practice guidelines for sarcoma treatment are applicable to AS, its unique aggressiveness and diverse tumor presentations necessitate dedicated and detailed clinical recommendations, which are currently lacking. Notably, considerations regarding surgical extent, radiation therapy (RT), and neoadjuvant/adjuvant chemotherapy vary significantly in localized disease, depending on each different site of onset. Indeed, AS are one of the sarcoma types most sensitive to cytotoxic chemotherapy. Despite this, uncertainties persist regarding optimal management across different clinical presentations, highlighting the need for further investigation through clinical trials. The Italian Sarcoma Group (ISG) organized a consensus meeting on April 1st, 2023, in Castel San Pietro, Italy, bringing together Italian sarcoma experts from several disciplines and patient representatives from "Sofia nel Cuore Onlus" and the ISG patient advocacy working group. The objective was to develop specific clinical recommendations for managing localized AS within the existing framework of sarcoma clinical practice guidelines, accounting for potential practice variations among ISG institutions. The aim was to try to standardize and harmonize clinical practices, or at least highlight the open questions in the local management of the disease, to define the best evidence-based practice for the optimal approach of localized AS and generate the recommendations presented herein., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: None of the authors has any interests to report directly related to this manuscript. Outside the scope of this manuscript: Elena Palassini, Institutional Research Funding: Deciphera Pharmaceuticals, Blueprint Medicines, Cogent Biosciences, Amgen/Dompè, Bayer, GlaxoSmith Kline, Novartis, Pfizer, PharmaMar, Eisai, Eli Lilly, Advenchen Laboratories , Arog, Epizyme, Karyopharm Therapeutics, SpringWorks Ther,Daiichi Sankyo, Boehringer Ingelheim, Rain Therapeutics, Foghorn Ther Inc, Hutchinson MediPharam Lt, INBRX, PTC Ther. Giacomo Giulio Baldi, consulting fees from Eli Lilly, Pharmamar, AboutEvents; honoraria from Pharmamar, Eli Lilly, Glaxo Smith Kline, Merck Sharp & Dome, Eisai, Istituto Gentili; support for attending meetings and/or travels from Novartis, Pharmamar, Eli Lilly; participation on advisory board from Pharmamar, Eli Lilly, Glaxo Smith Kline, Merck Sharp & Dome, Eisai. Sara Sulfaro, Marta Barisella, Giuseppe Bianchi, Domenico Campanacci, Marco Fiore, Marco Gambarotti, Massimiliano Gennaro, Carlo Morosi, no conflict of interests to declare. Federico Navarria, travel grants from Pharmamar, Boehringer Ingelheim. Claudia Sangalli, advisory board from Boehringer Ingelheim, Astra Zeneca. Rossella Bertulli, travel grants from PharmaMar. Institutional Research Funding: Deciphera Pharmaceuticals, Blueprint Medicines, Cogent Biosciences, Amgen/Dompè, Bayer, GlaxoSmith Kline, Novartis, Pfizer, PharmaMar, Eisai, Eli Lilly, Advenchen Laboratories , Arog, Epizyme, Karyopharm Therapeutics, SpringWorks Ther,Daiichi Sankyo, Boehringer Ingelheim, Rain Therapeutics, Foghorn Ther Inc, Hutchinson MediPharam Lt, INBRX, PTC Ther. Alexia Bertuzzi, Roberto Biagini, Angela Bonadonna, Antonella Brunello, Dario Callegaro, no conflict of interests to declare. Ferdinando Cananzi, speaking fee from Istituto Gentili. Marco Cianchetti, Paola Collini(,) Danila Comandini, Annalisa Curcio, no conflict of interests to declare. Lorenzo D’Ambrosio, advisory board: PSI CRO Italy, GSK, AstraZeneca, Boehringer Ingelheim, Eisai. Meeting participation: GSK, AstraZeneca, PharmaMar. Martino De Pas, participation on advisory board from Glaxo Smith Kline, Boehringer Ingelheim. Trial support from: Pfizer, BluPrint Medicine, Gilead, Amgen, Merck. Angelo Paolo Dei Tos, no conflict of interests to declare. Virginia Ferraresi, Travel grants from PharmaMar, Gentili, Boehringer Ingelheim. Advisory Board: SERB Pharmaceuticals. Andrea Ferrari, Alessandro Franchi, no conflict of interests to declare. Anna Maria Frezza, Institutional Research Funding: Deciphera Pharmaceuticals, Blueprint Medicines, Cogent Biosciences, Amgen/Dompè, Bayer, GlaxoSmith Kline, Novartis, Pfizer, PharmaMar, Eisai, Eli Lilly, Advenchen Laboratories , Arog, Epizyme, Karyopharm Therapeutics, SpringWorks Ther,Daiichi Sankyo, Boehringer Ingelheim, Rain Therapeutics, Foghorn Ther Inc, Hutchinson MediPharam Lt, INBRX, PTC Ther. Elena Fumagalli, Advisory Board from Deciphera Pharmaceuticals. Institutional Research Funding: Deciphera Pharmaceuticals, Blueprint Medicines, Cogent Biosciences, Amgen/Dompè, Bayer, GlaxoSmith Kline, Novartis, Pfizer, PharmaMar, Eisai, Eli Lilly, Advenchen Laboratories , Arog, Epizyme, Karyopharm Therapeutics, SpringWorks Ther,Daiichi Sankyo, Boehringer Ingelheim, Rain Therapeutics, Foghorn Ther Inc, Hutchinson MediPharam Lt, INBRX, PTC Ther. Matteo Ghilli, Daniela Greto, no conflict of interests to declare. Giovanni Grignani, advisory board from Pharmamar, Incyte, Merck, Novartis, Deciphera,Bayer. Michele Guida, advisory board from Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre. Toni ibrahim, advisory board and consultation fees from Amgen, Glaxosmithkline, PharMamar and Istituto Gentili. Travel grants from Istitaka Gentili and Pharmamar. Marco Krengli, Roberto Luksch, Andrea Marrari, Marinella Mastore, Alessandra Merlini, no conflict of interests to declare. Giuseppe Maria Milano, Advisory board from Bayer, GSK, SERBS Pharmaceuticals. Piera Navarria, Maria Abbondanza Pantaleo, Antonina Parafioriti, no conflict of interests to declare. Ilaria Pellegrini, Institutional Research Funding: Deciphera Pharmaceuticals, Blueprint Medicines, Cogent Biosciences, Amgen/Dompè, Bayer, GlaxoSmith Kline, Novartis, Pfizer, PharmaMar, Eisai, Eli Lilly, Advenchen Laboratories , Arog, Epizyme, Karyopharm Therapeutics, SpringWorks Ther,Daiichi Sankyo, Boehringer Ingelheim, Rain Therapeutics, Foghorn Ther Inc, Hutchinson MediPharam Lt, INBRX, PTC Ther. Elisabetta Pennacchioli, Marco Rastrelli, Elisabetta Setola, Salvatore Tafuto, Salvatore Turano, Sergio Valeri, Bruno Vincenzi, Viviana Vitolo, Andrei Ivanescu, Fiammetta Paloschi, no conflict of interests to declare. Paolo Giovanni Casali, Institutional Research Funding: Deciphera Pharmaceuticals, Blueprint Medicines, Cogent Biosciences, Amgen/Dompè, Bayer, GlaxoSmith Kline, Novartis, Pfizer, PharmaMar, Eisai, Eli Lilly, Advenchen Laboratories , Arog, Epizyme, Karyopharm Therapeutics, SpringWorks Ther,Daiichi Sankyo, Boehringer Ingelheim, Rain Therapeutics, Foghorn Ther Inc, Hutchinson MediPharam Lt, INBRX, PTC Ther. Alessandro Gronchi, no conflict of interests to declare. Silvia Stacchiotti, personal financial interests (honoraria, consultancy or advisory role): Aadi, Astex Pharmaceuticals, Bavarian Nordic, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Deciphera, Epizyme, Gentili, GSK, Agenus, Ikena, MaxiVAX, Novartis, PharmaMar, Pharma Essentia, Rain Therapeutics, Servier. Support for attending meetings and/or travel Pharmamar; Institutional financial interests: Advenchen, Bayer, Blueprint, Daiichi Sankyo, Deciphera, Epizyme, Eli Lilly, GSK, Hutchinson, Inhibrx, Karyopharm, Novartis, PharmaMar, Rain Therapeutics, SpringWorks; unpaid Member of the Scientifc Advisory Board of the Chordoma Foundation, Member of the Scientifc Advisory Board of the Desmoid Foundation, Member of the Scientifc Advisory Board of the Epithelioid Hemangioendothelioma Group, Member of the Scientifc Advisory Board of the Leiomyosarcoma Foundation., (Copyright © 2024. Published by Elsevier Ltd.)

Prostatic acinar adenocarcinoma accounts for approximately 95% of prostate cancer (CaP) cases. The remaining 5% of histologic subtypes of CaP are known to be more aggressive and have recently garnered substantial attention. These histologic subtypes - namely, prostatic ductal adenocarcinoma (PDA), intraductal carcinoma of the prostate (IDC-P), and cribriform carcinoma of the prostate (CC-P) - typically exhibit distinct growth characteristics, genomic features, and unique oncologic outcomes. For example, PTEN mutations, which cause uncontrolled cell growth, are frequently present in IDC-P and CC-P. Germline mutations in homologous DNA recombination repair (HRR) genes (e.g., BRCA1, BRCA2, ATM, PALB2, and CHEK2) are discovered in 40% of patients with IDC-P, while only 9% of patients without ductal involvement had a germline mutation. CC-P is associated with deletions in common tumor suppressor genes, including PTEN, TP53, NKX3-1, MAP3K7, RB1, and CHD1. Evidence suggests abiraterone may be superior to docetaxel as a first-line treatment for patients with IDC-P. To address these and other critical pathological attributes, this review examines the molecular pathology, genetics, treatments, and oncologic outcomes associated with CC-P, PDA, and IDC-P with the objective of creating a comprehensive resource with a centralized repository of information on PDA, IDC-P, and CC-P., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

At the end of 2019, the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China. Currently, it is breaking out globally and posing a serious threat to public health. The typically clinical characteristics of COVID-19 patients were fever and respiratory symptoms, and a proportion of patients were accompanied by extrapulmonary symptoms including cardiac injury, kidney injury, liver injury, digestive tract injury, and neurological symptoms. Angiotensin converting enzyme 2 (ACE2) has been proven to be a major receptor for SARS-CoV-2 and could mediate virus entry into cells. And transmembrane protease serine 2 (TMPRSS2) could cleave the spike (S) protein of SARS-CoV-2, which facilitates the fusion of SARS-CoV-2 and cellular membranes. The mRNA expressions of both ACE2 and TMPRSS2 were observed in the heart, digestive tract, liver, kidney, brain and other organs. SARS-CoV-2 may have a capacity to infect extrapulmonary organs due to the expressions of ACE2 and TMPRSS2 in the cells and tissues of these organs. It seems that there is a potential involvement of ACE2 and TMPRSS2 expressions in the virus infection of extrapulmonary organs and the manifestation of symptoms related to these organs in patients with COVID-19. Here, we revealed the expressions of ACE2 and TMPRSS2 in extrapulmonary organs, and we also summarized the clinical manifestation and the management of extrapulmonary complications in patients with COVID-19.

Both diabetes and osteoporosis are assuming epidemic proportions throughout the world. Accumulating data suggest that both types 1 and 2 diabetes are associated with an increased risk of fragility fractures. This increased risk appears to be largely independent of bone mineral density (BMD) which is most often noted to be low in type 1 diabetes and normal or increased in type 2 diabetes. This review explores the clinical characteristics of bone fragility in patients with diabetes and highlights studies that have evaluated BMD and fracture prediction tools in these patients. It also briefly reviews the current management principles of osteoporosis in diabetes, with special emphasis on the impact of diabetes medications on bone health as well as explores the efficacy of currently available antiosteoporosis pharmacotherapy in the diabetic population.

Background: Blackwater fever (BWF) is a severe syndrome occurring in patients with malaria upon antimalarial treatment, characterized by massive intravascular haemolysis and haemoglobinuria. BWF is a neglected condition and management recommendations are unavailable., Objectives: We performed a scoping review to appraise available data on clinical picture, treatment and physiopathology of BWF, which could guide rationally its clinical management., Methods: MEDLINE, EMBASE, LILACS, Web of Science, and Scopus databases, and the reference list of relevant publications, were searched. Papers reporting original data on BWF cases or investigating the physiopathology of BWF were eligible. Data regarding case characteristics, trigger event, clinical management and outcome were extracted. For papers investigating the physiopathology of BWF, study design and principal findings were extracted. No quality assessment was performed. Data are presented as numbers and percentages, and summary of findings, grouped by paper focus (clinical description or physiopathology)., Results: 101 papers were included. The majority of BWF cases were observed in autochthonous children (75.7%) and adults (15.3%), in contrast with historical perception that BWF patients were typically expatriates. Clinical management was described for 794 cases; corticosteroids were used in 23. Outcome was reported for 535 patients, with 18.1% mortality. The trigger was reported for 552 (47.5%) cases; in 70.4% identified as quinine. However, two RCT comparing artesunate and quinine for falciparum malaria treatment did not find significant difference in BWF occurrence after their administration. Two case-control studies did not find significant difference in G6PDH deficiency between malaria patients with and without BWF., Conclusions: The physiopathology and optimal treatment of BWF remain similarly unknown as they were over a century ago. Empirical supporting treatment approach seems reasonable, while change of antimalarial drug and use of corticosteroids remain object of debate., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Multi-drug and extensively drug-resistant tuberculosis (MDR/XDR-TB) are considered a serious threat for TB control and elimination. The outcome of these patients is still largely unsatisfactory as of today, with treatment success rates being consistently below 50% at global level. The World Health Organization (WHO) recommends that management of MDR-TB cases is supported by a specialized team, including complementary medical professionals able to cover several perspectives (clinical, both for adults and children; surgical; radiological; public health; psychological; nursing, among others). Implementation of such a body (known as Consilium in most of the former Soviet Union countries) is often a pre-requisite to apply for international TB control funding and concessionally priced medicines to treat M/XDR-TB cases. The primary objective of the ERS/WHO TB Consilium is to provide clinical consultation for drug-resistant TB and other difficult-to-treat TB cases, including co-infection with HIV and paediatric cases. Through technical guidance to clinicians managing complex TB cases, the main contribution and outcome of the initiative will be a public health response aimed at achieving correct treatment of affected patients and preventing further development of drug resistance. The Consilum's secondary objective is to ensure monitoring and evaluation of clinical practices on the ground (diagnosis, treatment and prevention).

Objectives: Little is known about how cognitive and behavioural decline in MND is managed clinically. This review aimed to summarise clinical management approaches of cognitive and behavioural decline in MND reported in peer-reviewed and grey literature., Methods: A scoping review was conducted across Embase, Medline, Psychinfo and Emcare in October 2022. Grey literature was also searched across Google Scholar and Google in October 2022., Results: A total of N = 26 studies and 8 documents were included. Thematic analysis revealed six key areas of clinical management: i. Assessment, ii. Education, iii. Advance Care Planning, iv. Adaptation of Care Plan, v. Communication and vi. Carer Support., Conclusions: The literature on management of cognitive and behavioural decline in MND is sparse. Most peer-reviewed literature consists of expert commentary and there is a lack of primary data to guide practitioners and families on how to manage cognitive and behavioural change in MND., Practice Implications: Determining as early as practicable the presence of cognitive and behavioural changes in pwMND will enable practitioners to make adaptations to communication, provide education and supported decision-making for forward planning. This will enable individualised care, planned in partnership with families with MND, which incorporates personal needs and wishes., Competing Interests: Declaration of Competing Interest There are NIL competing interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Tuberculosis (TB) is an important public health issue in Taiwan and worldwide. Taiwan has made major progress in combating TB in the past 40 years. However, childhood TB still constitutes a significant challenge in disease control. From January to mid December 2011, 369 new cases of pediatric TB were confirmed. The relatively low case number and variable clinical presentations made it difficult for early detection. Latent TB infections in children also pose further complexity in clinical management. Knowledge of the clinical features of active and latent TB infection is crucial for efficient TB control.

Los países prosperan sobre una base económica que permita desarrollar las potencialidades humanas en una sociedad que no renuncie a grandes logros, como el del estado del bienestar. Ello requiere que sus "reglas de juego", sus instituciones formales e informales, hagan individualmente atractivo lo socialmente conveniente. Mejorar el gobierno sanitario, también en su faceta de control de la corrupción, y contribuir a que España salga de la actual crisis económica, constituyen dos caras de la misma moneda. La caracterización del gobierno sanitario en España y el análisis de su impacto en las políticas de salud, la gestión de las organizaciones sanitarias y la práctica clínica, -permite elaborar una agenda tan ambiciosa como factible de las tareas pendientes que los profesionales sanitarios -en sentido muy amplio- y los responsables sociales debemos acometer con el apoyo ciudadano.Countries thrive on an economic foundation capable of facilitating the fulfillment of human potential in a society that does not renounce major achievements such as the welfare state. A necessary condition is that the "rules of the game", formal and informal institutions, make what is socially desirable individually attractive. Improving health governance, including its dimension of controlling corruption, and helping Spain out of the current economic crisis are two sides of the same coin. Characterization of health system governance in Spain and analysis of the impact of this governance on health policy, management of healthcare organizations and clinical practice allows an ambitious and feasible agenda to be drawn up of the remaining tasks that health professionals -broadly defined- and social actors should undertake with the support of citizens.

Excessive trabeculation, often referred to as "noncompacted" myocardium, has been described at all ages, from the fetus to the adult. Current evidence for myocardial development, however, does not support the formation of compact myocardium from noncompacted myocardium, nor the arrest of this process to result in so-called noncompaction. Excessive trabeculation is frequently observed by imaging studies in healthy individuals, as well as in association with pregnancy, athletic activity, and with cardiac diseases of inherited, acquired, developmental, or congenital origins. Adults with incidentally noted excessive trabeculation frequently require no further follow-up based on trabecular pattern alone. Patients with cardiomyopathy and excessive trabeculation are managed by cardiovascular symptoms rather than the trabecular pattern. To date, the prognostic role of excessive trabeculation in adults has not been shown to be independent of other myocardial disease. In neonates and children with excessive trabeculation and normal or abnormal function, clinical caution seems warranted because of the reported association with genetic and neuromuscular disorders. This report summarizes the evidence concerning the etiology, pathophysiology, and clinical relevance of excessive trabeculation. Gaps in current knowledge of the clinical relevance of excessive trabeculation are indicated, with priorities suggested for future research and improved diagnosis in adults and children., Competing Interests: Funding Support and Author Disclosures Dr Petersen has received support from the National Institute for Health and Care Research Barts Biomedical Research Centre; and has consulted with Circle Cardiovascular Imaging Inc. Dr Friedrich has received support from the McGill Health Centre Foundation; has served as an advisor to and is a shareholder of Circle Cardiovascular Imaging Inc; and is a founder and shareholder of Area19 Medical Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To determine if shorter courses of antibiotic therapy for group A Streptococcus (GAS) bacteremia are associated with excess mortality., Methods: In this retrospective study of consecutive cases of GAS bacteremia in tropical Australia, the duration of antibiotic therapy was correlated with 90-day all-cause mortality., Results: There were 286 episodes of GAS bacteremia; the patients' median (interquartile range) age was 60 (48-71) years and 169/286 (59.1%) patients identified as an Indigenous Australian. There were 227/286 (79.4%) patients with a significant comorbidity. The all-cause 90-day mortality was 16/286 (5.6%); however, 12/16 (81.3%) patients died while still receiving their initial course of antibiotics and only 7/16 (43.8%) deaths were directly attributable to the GAS infection. After excluding patients who died while taking their initial course of antibiotics and those in whom the duration of therapy was uncertain, there was no difference in 90-day mortality between patients receiving ≤5 days of intravenous antibiotics and those receiving longer courses (1/137 [0.7%] vs 3/107 [2.8%], P-value = 0.32) nor in patients receiving ≤10 days of total therapy and those receiving longer courses (1/67 [1.5%] vs 3/178 [1.7%], P-value = 1.0)., Conclusion: Even among patients with significant comorbidity, shorter antibiotic courses for GAS bacteremia are not associated with excess mortality., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Las listas de espera para recibir asistencia no urgente, en procesos diagnósticos o tratamientos, se dan fundamentalmente en los sistemas sanitarios de financiación pública como el español y otros muchos países europeos. Si éstas son moderadas, pueden ser útiles en el proceso de gestión de estos pacientes y son aceptadas por profesionales y usuarios. Las listas de espera para intervenciones quirúrgicas se pueden interpretar, erróneamente, como un simple desajuste entre la demanda y la oferta de un determinado procedimiento. Si así fuera, sólo deberíamos ir aumentando los recursos hasta terminar con las listas. Sin embargo, existen muchas evidencias de que el aumento aislado de los recursos no es la solución, ya que el tiempo medio de espera disminuye pero la lista se alarga por la cola. Serán necesarias, pues, otras medidas de gestión. Es necesario gestionar las listas, tanto en el plano social, de administración sanitaria y, sobre todo, en el ámbito del centro sanitario. La gestión clínica en los servicios y la gestión de cada profesional, con criterios de inclusión de evidencia científica en la indicación y en los resultados esperados de cada paciente (efectividad del procedimiento), y con criterios éticos y de eficiencia en la utilización de recursos, priorizando por gravedad, probabilidad de mejora y criterios sociales, es una obligación ineludible para mejorar el problema de las listas de espera. En este proceso de priorización, la sociedad debe tener su voz, su opinión, pues existen factores no médicos que pueden influir en la distribución y priorización de recursos. En este camino existen experiencias en otros países que deberíamos analizar. Finalmente, como decía Archie Cochrane¹, «todo tratamiento eficaz ha de ser gratuito», que, dicho de otra manera, sería: no está justificada la financiación en el sistema público de procedimientos que no aporten un beneficio significativo para el paciente.Waiting lists for non-urgent medical care, in diagnostic or therapeutic procedures, occur mainly in public health systems such as those found in Spain and many other European countries. If waiting lists are moderate they can be useful in the process of managing these patients and are accepted by health professionals and health services users. Waiting lists for surgical procedures can be interpreted, erroneously, as a simple imbalance between the supply and demand for a particular procedure. If that were the case, we would only have to progressively increase resources until eliminating the lists. However, considerable evidence suggests that the isolated increase of resources does not solve the problem since the mean waiting time is reduced but the waiting list becomes longer. Therefore, other management measures are required. The management of waiting lists is necessary at the levels of society, health administration and especially health centers. Clinical management by departments and individual health professionals is essential, using the criteria of inclusion of scientific evidence in the indication for treatment and in the results expected for each patient (effectiveness of the procedure) as well as ethical criteria and considerations of resource use efficiency. Prioritizing patients according to severity, probability of improvement and social criteria is an unavoidable obligation in improving the problem of waiting lists. In this process of prioritization, society should also be able to voice an opinion since non-medical factors may influence the distribution and prioritization of resources and in this context the experience of other countries should be analyzed. Finally, as Archie Cochrane said "all effective treatment should be free" which, put another way would be: in a public system, the financing of procedures that do not provide significant benefits to patients is not justified.