Search Results (941)

Background/Objectives: Patients with breast cancer who do not achieve a complete response to neoadjuvant chemotherapy (NAC) may benefit from intensified adjuvant systemic therapy. However, such treatment escalation is typically delayed until after tumour resection, which occurs several months into the treatment course. Quantitative ultrasound (QUS) can detect early microstructural changes in tumours and may enable timely identification of non-responders during NAC, allowing for earlier treatment intensification. In our previous prospective observational study, 100 breast cancer patients underwent QUS imaging before and four times during NAC. Machine learning algorithms based on QUS texture features acquired in the first week of treatment were developed and achieved 78% accuracy in predicting treatment response. In the current study, we aimed to validate these algorithms in an independent prospective cohort to assess reproducibility and confirm their clinical utility. Methods: We included breast cancer patients eligible for NAC per standard of care, with tumours larger than 1.5 cm. QUS imaging was acquired at baseline and during the first week of treatment. Tumour response was defined as a ≥30% reduction in target lesion size on the resection specimen compared to baseline imaging. Results: A total of 51 patients treated between 2018 and 2021 were included (median age 49 years; median tumour size 3.6 cm). Most were estrogen receptor–positive (65%) or HER2-positive (33%), and the majority received dose-dense AC-T (n = 34, 67%) or FEC-D (n = 15, 29%) chemotherapy, with or without trastuzumab. The support vector machine algorithm achieved an area under the curve of 0.71, with 86% accuracy, 91% specificity, 50% sensitivity, 93% negative predictive value, and 43% positive predictive value for predicting treatment response. Misclassifications were primarily associated with poorly defined tumours and difficulties in accurately identifying the region of interest. Conclusions: Our findings validate QUS-based machine learning models for early prediction of chemotherapy response and support their potential as non-invasive tools for treatment personalization and clinical trial development focused on early treatment intensification. Full article

Early rehabilitation is essential for restoring functional recovery in patients with stroke, particularly during the early phase of post-acute care (PAC), or the subacute stage. We aimed to evaluate the effectiveness of a 7-week PAC rehabilitation program in improving muscle strength, physical performance, and functional recovery. A total of 219 inpatients with stroke in the subacute stage were initially recruited from the PAC ward of a regional teaching hospital in Northern Taiwan, with 79 eligible patients—within 1 month of an acute stroke—included in the analysis. The program was delivered 5 days per week, with 3–4 sessions daily (20–30 min each, up to 120 min daily), comprising physical, occupational, and speech–language therapies. Sociodemographic data, muscle strength, physical performance (Berg Balance Scale [BBS], gait speed, and 6-minute walk test [6MWT]), and functional recovery (modified Rankin Scale [mRS], Barthel Index [BI], Instrumental Activities of Daily Living [IADL], and Fugl–Meyer assessment: sensory and upper extremity) were collected at baseline, 3 weeks, and 7 weeks. Generalized estimating equations analyzed program effectiveness. Among the 56 patients (70.9%) who completed the program, significant improvements were observed in the muscle strength of both the affected upper (B = 0.93, p < 0.001) and lower limbs (B = 0.88, p < 0.001), as well as in their corresponding unaffected limbs; in physical performance, including balance (BBS score: B = 9.70, p = 0.003) and gait speed (B = 0.23, p = 0.024); and in functional recovery, including BI (B = 19.5, p < 0.001), IADL (B = 1.48, p < 0.001), and mRS (B = −0.13, p = 0.028). These findings highlight the 7-week PAC rehabilitation program as an effective strategy during the critical recovery phase for patients with stroke. Full article

Cancer disparities in low- and middle-income countries (LMICs) arise from multifaceted interactions between environmental exposures, infectious agents, and systemic inequities, such as limited access to care. The exposome, a framework encompassing the totality of non-genetic exposures throughout life, offers a powerful lens for understanding these disparities. In LMICs, populations are disproportionately affected by air and water pollution, occupational hazards, and oncogenic infections, including human papillomavirus (HPV), hepatitis B virus (HBV), Helicobacter pylori (H. pylori), human immunodeficiency virus (HIV), and neglected tropical diseases, such as schistosomiasis. These infectious agents contribute to increased cancer susceptibility and poor outcomes, particularly in immunocompromised individuals. Moreover, climate change, food insecurity, and barriers to healthcare access exacerbate these risks. This review adopts a population-level exposome approach to explore how environmental and infectious exposures intersect with genetic, epigenetic, and immune mechanisms to influence cancer incidence and progression in LMICs. We highlight the critical pathways linking chronic exposure and inflammation to tumor development and evaluate strategies such as HPV and HBV vaccination, antiretroviral therapy, and environmental regulation. Special attention is given to tools such as exposome-wide association studies (ExWASs), which offer promise for exposure surveillance, early detection, and public health policy. By integrating exposomic insights into national health systems, especially in regions such as sub-Saharan Africa (SSA) and South Asia, LMICs can advance equitable cancer prevention and control strategies. A holistic, exposome-informed strategy is essential for reducing global cancer disparities and improving outcomes in vulnerable populations. Full article

Objectives: Febrile neutropenia is a common oncologic emergency with significant morbidity and mortality. Although the MASCC (Multinational Association for Supportive Care in Cancer) score is widely used for risk stratification, its limited sensitivity and lack of laboratory parameters reduce its prognostic utility. This study aimed to evaluate whether incorporating serum lactate and CRP measurements into the MASCC score enhances its predictive performance for hospital admission and the 30-day mortality. Methods: This retrospective diagnostic accuracy study included adult patients diagnosed with febrile neutropenia in the emergency department of a tertiary care hospital between January 2021 and December 2024. The original MASCC score was calculated, and three modified models were derived: the MASCC-L (lactate/MASCC), MASCC-C (CRP/MASCC) and MASCC-LC models (CRP × lactate/MASCC). The predictive accuracy for hospital admission and the 30-day all-cause mortality was assessed using ROC analysis. Results: A total of 269 patients (mean age: 67.6 ± 12.4 years) were included; the 30-day mortality was 3.0%. The MASCC-LC model demonstrated the highest discriminative ability for mortality prediction (area under the curve (AUC): 0.995; sensitivity: 100%; specificity: 98%). For hospital admission prediction, the MASCC-C model had the highest specificity (81%), while the MASCC-LC model showed the best balance of sensitivity and specificity (both 73%). All the modified models outperformed the original MASCC score regarding both endpoints. Conclusions: Integrating lactate and CRP measurements into the MASCC score significantly improves its prognostic accuracy for both mortality and hospital admission in febrile neutropenic patients. The MASCC-LC model, relying on only three objective parameters, may serve as a practical and efficient tool for early risk stratification in emergency settings. Full article

Background: Post-traumatic trigeminal neuropathic pain (PTTNP) is a chronic condition often caused by dental procedures such as implant placement or tooth extraction. It involves persistent pain and sensory disturbances, negatively affecting the quality of life of patients. Methods: This retrospective observational study was conducted at Chosun University Dental Hospital and included 120 patients diagnosed with PTTNP involving the orofacial region. Patient data were collected between January 2014 and December 2023. Among them, 79 patients (65.8%) developed PTTNP following dental implant placement, with a total of 121 implants analyzed. The inferior alveolar nerve was most frequently involved. Clinical factors, including the time to treatment, removal of the causative factor, the Sunderland injury grade, and the type of treatment, were evaluated. Pain intensity and sensory changes were assessed using the visual analog scale (VAS). Results: Treatment initiated within the early post-injury period, commonly regarded as within three months, and implant removal tended to improve outcomes. Pharmacological therapy was the most commonly employed modality, particularly gabapentinoids (e.g., gabapentin, pregabalin) and tricyclic antidepressants such as amitriptyline. However, combined therapy, which included pharmacologic, physical, and surgical approaches, was associated with the greatest sensory improvement. Conclusions: Prompt, multidisciplinary intervention may enhance recovery in patients with PTTNP. Implant-related injuries require careful management, and multimodal strategies appear more effective than monotherapies. Full article

Background/Objective: In-hospital cardiac arrest has high incidence and poor survival rates, posing a significant healthcare challenge. It is important to intervene in the hours before the cardiac arrest to prevent poor outcomes. The modified early warning score (MEWS) is a validated tool for identifying a deteriorating patient. It is an aggregate of vital signs and level of consciousness. We retrospectively evaluated MEWS for trends that might predict patient outcomes. Methods: We performed a single-center, one-year, retrospective study. A comprehensive review was conducted for patients aged 18 years and above who experienced a cardiac arrest. Cases that occurred within an intensive care unit, emergency department, during a procedure, or outside the hospital were excluded. A total of 87 cases met our predefined inclusion criteria. We collected data at 12 h, 6 h and 1 h time periods prior to the cardiac arrest. A trend analysis using a linear model with analysis of variance with Bonferroni correction was performed. Results: Out of 87 patients included in the study, 59 (67.8%) had an immediate return of spontaneous circulation (ROSC). Among those who achieved ROSC, 41 (69.5%) died during the admission. Only 20.7% of the patients that sustained a cardiac arrest survived to discharge. A significant increase in the average MEWS was noted from the 12 h period (MEWS = 3.95 ± 2.4) to the 1 h period (MEWS = 5.98 ± 3.5) (p ≤ 0.001) and the 6 h period (4.65 ± 2.6) to the 1 h period (5.98 ± 3.5) (p = 0.023) prior to cardiac arrest. Conclusions: An increase in the MEWS may be a valuable tool in identifying at-risk patients and provides an opportunity to intervene at least 6 h before a cardiac arrest event. Further research is needed to validate the results of our study. Full article

Temporomandibular disorders (TMDs) encompass a heterogeneous group of musculoskeletal and neuromuscular conditions affecting the temporomandibular joint (TMJ) and masticatory system. Due to academic stress and parafunctional habits, dental students may be particularly vulnerable to TMD. Objective: To determine the prevalence of TMD symptoms and their psychosocial and functional correlates among students at the Faculty of Dental Medicine, UMPh Iasi, Romania, using the diagnostic criteria for TMD (DC/TMD) self-report axis and axis II instruments. Methods: In this cross-sectional survey, 356 volunteer students (66.0% female; mean age, 22.9 ± 3.6 years) out of a total population of 1874 completed an online DC/TMD–based questionnaire. Axis I assessed orofacial pain, joint noises, and mandibular locking. Axis II instruments included the Graded Chronic Pain Scale (GCPS), Jaw Functional Limitation Scale (JFLS-20), Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Oral Behaviors Checklist (OBC). Descriptive statistics summarized frequencies, means, and standard deviations; χ² tests and t-tests compared subgroups by sex; Pearson correlations explored relationships among continuous measures (α = 0.05). Results: A total of 5% of respondents reported orofacial pain in the past 30 days; 41.6% observed TMJ noises; 19.7% experienced locking episodes. Mean JFLS score was 28.3 ± 30.5, with 4.8% scoring > 80 (severe limitation). Mean PHQ-9 was 5.96 ± 5.37 (mild depression); 15.5% scored ≥ 10. Mean GAD-7 was 5.20 ± 4.95 (mild anxiety); 16.0% scored ≥ 10. Mean OBC score was 12.3 ± 8.5; 30.1% scored ≥ 16, indicating frequent parafunctional habits. Symptom prevalence was similar by sex, except temporal headache (43.4% females vs. 24.3% males; p = 0.0008). Females reported higher mean scores for pain intensity (2.09 vs. 1.55; p = 0.0013), JFLS (32.5 vs. 18.0; p < 0.001), PHQ-9 (6.43 vs. 5.16; p = 0.048), and OBC (13.9 vs. 9.7; p = 0.0014). Strong correlation was observed between PHQ-9 and GAD-7 (r = 0.74; p < 0.001); moderate correlations were observed between pain intensity and PHQ-9 (r = 0.31) or GAD-7 (r = 0.30), between JFLS and pain intensity (r = 0.33), and between OBC and PHQ-9 (r = 0.39) (all p < 0.001). Conclusions: Nearly half of dental students reported TMD symptoms, with appreciable functional limitation and psychosocial impact. Parafunctional behaviors and psychological distress were significantly associated with pain and dysfunction. These findings underscore the need for early screening, stress-management interventions, and interdisciplinary care strategies in the dental student population. Full article

Background/Objectives: Inborn errors of immunity (IEIs) represent a wide spectrum of diseases characterized by a predisposition to recurrent infections, as well as increased susceptibility to autoimmune, atopic, and autoinflammatory diseases and malignancies. The aim of this study was to report the registry-based frequency and describe the clinical characteristics of IEIs among patients in the Republic of Kazakhstan. Methods: We analyzed data from 269 patients belonging to 204 families who were either self-referred or referred by healthcare providers to the University Medical Center of Nazarbayev University with suspected IEIs. All patients resided in various regions across Kazakhstan. Results: A total of 269 diagnosed cases were identified in the national registry. The estimated prevalence was 1.3 per 100,000 population. The gender ratio was nearly equal, with 139 males and 130 females. The median age at diagnosis was 5 years (range: 1 month to 70 years), while the mean age was 11.3 years. The most common diagnosis was humoral immunodeficiency, observed in 120 individuals (44.6%), followed by complement deficiencies in 83 individuals (30.8%). Combined immunodeficiencies with syndromic features were found in 35 patients (13%), and phagocytic cell defects were identified in 12 patients (4.5%). The predominant clinical manifestations included severe recurrent infections and autoimmune cytopenias, while atopic and autoinflammatory symptoms were reported less frequently. Conclusions: These findings contribute to a better understanding of the registry-based distribution and clinical spectrum of IEIs in Kazakhstan and underscore the importance of early diagnosis and targeted care for affected individuals. Full article

Sepsis remains a leading global cause of mortality, with delayed recognition and empirical antibiotic overuse fueling poor outcomes and rising antimicrobial resistance. This systematic scoping review evaluates the current landscape of artificial intelligence (AI) and machine learning (ML) applications in sepsis care, focusing on early detection, personalized antibiotic management, and resistance forecasting. Literature from 2019 to 2025 was systematically reviewed following PRISMA-ScR guidelines. A total of 129 full-text articles were analyzed, with study quality assessed via the JBI and QUADAS-2 tools. AI-based models demonstrated robust predictive performance for early sepsis detection (AUROC 0.68–0.99), antibiotic stewardship, and resistance prediction. Notable tools, such as InSight and KI.SEP, leveraged multimodal clinical and biomarker data to provide actionable, real-time support and facilitate timely interventions. AI-driven platforms showed potential to reduce inappropriate antibiotic use and nephrotoxicity while optimizing outcomes. However, most models are limited by single-center data, variable interpretability, and insufficient real-world validation. Key challenges remain regarding data integration, algorithmic bias, and ethical implementation. Future research should prioritize multicenter validation, seamless integration with clinical workflows, and robust ethical frameworks to ensure safe, equitable, and effective adoption. AI and ML hold significant promise to transform sepsis management, but their clinical impact depends on transparent, validated, and user-centered deployment. Full article

Neuronal ceroid lipofuscinoses (NCLs) are paediatric neurodegenerative disorders that primarily affect the central nervous system (CNS). The high prevalence of gastrointestinal (GI) symptoms has prompted researchers and clinicians to move beyond an exclusively “brain-centric” perspective. At the molecular level, mutations in CLN genes lead to lysosomal dysfunction and impaired autophagy, resulting in intracellular accumulation of storage material that disrupts both central and enteric neuronal homeostasis. To systematically examine current clinical and preclinical knowledge on gut involvement in NCLs, with a focus on recent findings related to the enteric nervous system and gut microbiota. We conducted a systematic review following the PRISMA guidelines using PubMed as the sole database. Both clinical (human) and preclinical (animal) studies were included. A total of 18 studies met the inclusion criteria, focusing on gastrointestinal dysfunction, nervous system involvement, and gut microbiota. We found that the nature of GI symptoms was multifactorial in NCLs, involving not only the CNS but also the autonomic and enteric nervous systems, which were affected early by lysosomal deposits and enteric neuron degeneration. Of note, preclinical studies showed that gene therapy could improve not only CNS manifestations but also GI ones, which may have beneficial implications for patient care. While the role of the ENS seems to be clearer, that of gut microbiota needs to be further clarified. Current evidence from preclinical models highlighted alterations in the composition of the microbiota and suggested a possible influence on the progression and modulation of neurological symptoms. However, these results need to be confirmed by further studies demonstrating the causality of this relationship. GI involvement is a key feature of NCLs, with early impact on the enteric nervous system and possible links to gut microbiota. Although preclinical findings—particularly on gene therapy—are encouraging due to their dual impact on both CNS and GI manifestations, the causal role of the gut microbiota remains to be fully elucidated. In this context, the development of sensitive and specific outcome measures to assess GI symptoms in clinical trials is crucial for evaluating the efficacy of future therapeutic interventions. Full article

Objective: This study aimed to evaluate the relationship between the Prognostic Nutritional Index (PNI) and demographic characteristics, presenting complaints, clinical diagnoses, and patient outcomes in patients admitted to the emergency department for gastrointestinal (GI) emergencies. The predictive value of PNI for the clinical course of patients with GI emergencies was investigated. Method: This retrospective cross-sectional study included 583 patients with a diagnosis of GI emergencies in the emergency department of a tertiary university hospital between January 2021 and December 2024. Data such as age, sex, presenting complaints, final diagnosis, and emergency department outcomes (discharge, ward admission, and transfer to intensive care unit) were collected. The PNI value was calculated using serum albumin (g/dL) and total lymphocyte count (/mm³) with the formula PNI = 10 × albumin + 0.005 × lymphocyte. The PNI was calculated based on serum albumin levels and peripheral lymphocyte counts. Results: The mean age of the study group was 63.4 ± 17.4 years, and 52.1% of the patients were female. The number of patients with a PNI value < 38 was significantly higher in the intensive care unit (p < 0.001). PNI values were considerably lower, especially in patients diagnosed with malignancy, cirrhosis, and GI hemorrhage (X² = 71.387; p < 0.001). The PNI was an independent predictor of outcomes in patients with GI emergencies. The mean PNI was significantly higher in discharged patients but significantly lower in patients admitted to the intensive care unit (p < 0.002). The cut-off score for PNI was calculated using the median value, and the cut-off score for PNI was <38. Conclusion: PNI is a powerful biomarker for predicting the clinical severity and prognosis of patients with GI emergencies. Since it can be easily calculated from routine biochemical tests, it can be used as a practical and effective risk stratification tool. The evaluation of PNI, especially for the early detection of critically ill patients at high risk of malnutrition, may contribute to the reduction of morbidity and mortality through the timely initiation of appropriate supportive therapies. Full article

Background: Congenital insensitivity to pain with anhidrosis (CIPA) is a rare genetic disorder, often leading to injuries and serious infections. In 2018, we established a multidisciplinary clinic (MDC) to provide structured, proactive care. We assessed the MDC’s impact on hospitalizations, surgeries, and infection rates. Methods: A retrospective study of genetically confirmed CIPA patients, treated from 2014 to 2024. Data from electronic medical records were compared between the pre-MDC (2014–2017) and post-MDC (2018–2024) periods. The core MDC team includes an infectious disease specialist, orthopedic surgeon, and nurses. The patients are stratified according to their carriage of resistant organisms and are managed using strict infection control measures. Follow-ups are scheduled routinely or as needed. Treatment is guided by clinical findings and culture results. Results: A total of 59 patients were included in the study. The baseline age did not differ significantly between the two periods. Hospitalization rates declined by 30.7% (from 57.7 to 40.0 per 1000 days), and clinic visits decreased by 42.9% (25.5 to 14.6). Overall surgical rates remained stable (2.8 to 2.7), with a 61.9% decrease in eye surgeries and a 130.5% increase in elective tooth extractions. Infection rates increased by 52% (from 6.6 to 10.1 per 1000 days). Conclusions: The implementation of the MDC bundle led to reduced hospitalizations, clinic visits, and eye surgeries, alongside the increased use of elective tooth extractions and culture testing. Closer monitoring and early infection management contributed to fewer severe complications. These findings support the value of structured, proactive multidisciplinary care in improving outcomes for children with CIPA. Full article

Background/Objectives: Quality of life (QoL) is a valuable tool for evaluating treatment outcomes and identifying patients who may benefit from early supportive interventions. This study aimed to determine whether specific QoL results in patients with advanced rectal cancer could identify groups with an unfavourable prognosis in long-term follow-up. Methods: A total of 570 patients with advanced rectal cancer were prospectively assessed, during and up to five years after neoadjuvant radiochemotherapy, using the QLQ-C30 and QLQ-CR38 questionnaires. We analysed 27 functional and symptom-related scores to identify associations with overall survival, once at baseline, three times during therapy, and annually from years one to five post-therapy. Results: Poor quality of life scores were consistently associated with shorter overall survival. The functional scores of physical functioning, role functioning, and global health, as well as the symptom scores of fatigue, dyspnoea, and chemotherapy side effects, were highly significant for overall survival at nearly all time points except for the immediate preoperative assessment. Patients over the age of 64 with lower QoL scores showed a significantly reduced probability of survival in the follow-up period, and patients who reported poor QoL in at least two of the first three questionnaires during the initial phase of treatment showed significantly reduced overall survival. Conclusions: Early and repeated QoL assessments, particularly within the first weeks of therapy, offer critical prognostic value in advanced rectal cancer. Identifying patients with an unfavourable prognosis might allow faster interventions that could improve survival outcomes. Integrating QoL monitoring into routine clinical practice could enhance individualised care and support risk stratification. Full article

Background: Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease and a major cause of morbidity and mortality among preterm infants. Traditional diagnostic methods such as abdominal radiography have limited sensitivity in early disease stages, prompting interest in bowel ultrasound (BUS) as a complementary imaging modality. Objective: This scoping review aims to synthesize existing literature on the role of ultra sound in the early detection, diagnosis, and management of NEC, with emphasis on its diagnostic performance, integration into clinical care, and technological innovations. Methods: Following PRISMA-ScR guidelines, a systematic search was conducted across PubMed, Embase, Cochrane Library, and Google Scholar for studies published between January 2000 and December 2025. Inclusion criteria encompassed original research, reviews, and clinical studies evaluating the use of bowel, intestinal, or Doppler ultrasound in neonates with suspected or confirmed NEC. Data were extracted, categorized by study design, population characteristics, ultrasound features, and diagnostic outcomes, and qualitatively synthesized. Results: A total of 101 studies were included. BUS demonstrated superior sensitivity over radiography in detecting early features of NEC, including bowel wall thickening, portal venous gas, and altered peristalsis. Doppler ultrasound, both antenatal and postnatal, was effective in identifying perfusion deficits predictive of NEC onset. Neonatologist-performed ultrasound (NEOBUS) showed high interobserver agreement when standardized protocols were used. Emerging tools such as ultra-high-frequency ultrasound (UHFUS) and artificial intelligence (AI)-enhanced analysis hold potential to improve diagnostic precision. Point-of-care ultrasound (POCUS) appears feasible in resource-limited settings, though implementation barriers remain. Conclusions: Bowel ultrasound is a valuable adjunct to conventional imaging in NEC diagnosis. Standardized protocols, validation of advanced technologies, and out come-based studies are essential to guide its broader clinical adoption. Full article

Background: In advanced heart failure patients implanted with a fully magnetically levitated HeartMate 3 (HM3) Abbott left ventricular assist device (LVAD), it is unknown how the role of the LVAD outpatient clinic may affect the long-term survival after hospital discharge. Our objective is to share our standardized protocol for outpatient care, to describe the role of the LVAD outpatient clinic in postoperative long-term care after LVAD implantation, and to report survival. Methods: We retrospectively reviewed all patients implanted with HM3 LVAD in our institute between September 2015 and January 2025. Patients who received HeartWare Ventricular Assist Device (HVAD) and HeartMate 2 LVAD devices were excluded from our study, to ensure a homogenous cohort focusing on the latest and the only currently used LVAD device generation. We included a total of 48 patients. After LVAD patients are discharged from our center, they are followed in our outpatient clinic in 3-month intervals. During visits, bloodwork, EKG, wound inspection, and echocardiography are performed in addition to LVAD analysis. The role of the outpatient clinic is to detect early signs of deterioration or problems and act accordingly to prevent serious complications. Results: Thirty-three patients (68.7%) are still alive in 2025; two patients (4.2%) had a successful heart transplantation; and thirty-one patients (64.5%) are still on LVAD support. There were 210 total patient years of support. The mean time on device is 4.4 years. During the follow-up period we noticed 15 deaths (31.3%). Notably, there was no technical device-related death. Kaplan–Meier analysis estimated an overall survival rate of 97.9%, 92.8%, 83.7%, and 51.1% at 1, 2, 4, and 8 years, respectively. Conclusion: Strict control of patients after discharge in an outpatient clinic is essential for the long-term survival of these patients. A well-structured outpatient program is of utter importance to avoid LVAD-related complications and should be a cornerstone for the treatment, especially in non-transplant centers. Full article