Concepts of Cardiac Dyssynchrony and Dynamic Approach.

Cardiac conduction involves electrical activity from one myocyte to another, creating coordinated contractions in each. Disruptions in the conducting system, such as left bundle branch block (LBBB), can result in premature activation of specific regions of the heart, leading to heart failure and increased morbidity and mortality. Structural alterations in T-tubules and the sarcoplasmic reticulum can lead to dyssynchrony, a condition that can be treated by cardiac resynchronization therapy (CRT), which stands as a cornerstone in this pathology. The heterogeneity in patient responses underscored the necessity of improving the diagnostic approach. Vectocardiography, ultra-high-frequency ECG, 3D echocardiography, and electrocardiographic imaging seem to offer advanced precision in identifying optimal candidates for CRT in addition to the classic diagnostic methods. The advent of His bundle pacing and left bundle branch pacing further refined the approach in the treatment of dyssynchrony, offering more physiological pacing modalities that promise enhanced outcomes by maintaining or restoring the natural sequence of ventricular activation. HOT-CRT emerges as a pivotal innovation combining the benefits of CRT with the precision of His bundle or left bundle branch area pacing to optimize cardiac function in a subset of patients where traditional CRT might fall short.

Uncommon Presentation of Gastric Duplication Cyst with Left-Sided Portal Hypertension: A Case Report and Literature Review.

Gastric duplication cysts (GDCs) in adults are exceedingly rare, with only a few documented cases in medical literature. The spectrum of clinical presentations varies widely, ranging from asymptomatic to severe symptoms such as hematemesis, vomiting or abdominal pain. Among the less common complications associated with GDCs, segmental portal hypertension is a notable rarity. We present a compelling case report of a patient exhibiting signs of segmental portal hypertension, where ultrasound and echo-endoscopy revealed a sizable gastric duplication cyst as the underlying etiology. Recognizing the scarcity of literature on GDCs in adult patients, we conducted a thorough review to underscore the diagnostic significance of ultrasonography and endoscopic ultrasound (EUS) in accurately identifying these congenital anomalies. This case report and comprehensive literature review emphasize the pivotal role of EUS and abdominal ultrasound in achieving an accurate diagnosis of GDCs. By shedding light on the diagnostic and therapeutic intricacies, we aim to raise awareness among clinicians regarding this rare pathology and the importance of multimodal imaging approaches for optimal patient management.

A fractional perspective on the transmission dynamics of a parasitic infection, considering the impact of both strong and weak immunity.

Infectious disease cryptosporidiosis is caused by the cryptosporidium parasite, a type of parasitic organism. It is spread through the ingestion of contaminated water, food, or fecal matter from infected animals or humans. The control becomes difficult because the parasite may remain in the environment for a long period. In this work, we constructed an epidemic model for the infection of cryptosporidiosis in a fractional framework with strong and weak immunity concepts. In our analysis, we utilize the well-known next-generation matrix technique to evaluate the reproduction number of the recommended model, indicated by [Formula: see text]. As [Formula: see text], our results show that the disease-free steady-state is locally asymptotically stable; in other cases, it becomes unstable. Our emphasis is on the dynamical behavior and the qualitative analysis of cryptosporidiosis. Moreover, the fixed point theorem of Schaefer and Banach has been utilized to investigate the existence and uniqueness of the solution. We identify suitable conditions for the Ulam-Hyers stability of the proposed model of the parasitic infection. The impact of the determinants on the sickness caused by cryptosporidiosis is highlighted by the examination of the solution pathways using a novel numerical technique. Numerical investigation is conducted on the solution pathways of the system while varying various input factors. Policymakers and health officials are informed of the crucial factors pertaining to the infection system to aid in its control.

Challenges of Secondary Glaucoma Management Following Congenital Cataract Surgery, Penetrating Keratoplasty and Vitreoretinal Surgery.

Glaucoma is one of the world's leading causes of irreversible vision loss. It is often asymptomatic until it reaches an advanced stage, which can have a significant impact on patients' daily lives. This paper describes the case of a 50-year-old female patient who presented with acute onset of ocular pain, photophobia, and loss of visual acuity in her right eye (RE). The patient's medical history includes congenital cataracts, surgical aphakia, nystagmus, strabismus, amblyopia, and secondary glaucoma. Ophthalmological examination showed BCVA RE-hand movement, left eye (LE)-0.08 with an intraocular pressure (IOP) of 30 mmHg in RE and 16 mmHg in LE. Biomicroscopic examination of RE showed corneal graft, epithelial and endothelial edema, endothelial precipitates, corneal neovascularization, aphakia, and Ahmed valve superotemporally. Despite maximal topical and systemic treatment, Ahmed valve, and trabeculectomy, secondary glaucoma in the right eye remained refractory. Reimplantation of an Ahmed valve was performed. This resulted in a favorable outcome with increased visual acuity and controlled intraocular pressure. The combination of aphakia, penetrating keratoplasty, and secondary glaucoma is a challenge for any surgeon. It is important that both the perioperative risks and the possible complications are carefully assessed in each patient, especially if associated pathology is present.

Laparoscopic Management of Multiple Liver, Omental, Mesenteric, Peritoneal, and Round Ligament Hydatid Cysts-A Rare Report of a Case and a Systematic Literature Review.

Hydatid cyst disease is a parasitic ailment with an endemic nature, predominantly affecting geographical areas with a tradition in animal husbandry. The most common localization of hydatid disease is in the liver (60%), followed by the lungs, with other organ localizations comprising less than 10%. The surgical approach to this condition can be carried out through open surgery or laparoscopy. The coexistence of hepatic and intraperitoneal hydatidosis often leads to the preference for open surgery. We performed a literature review aiming to retrieve data regarding demographic characteristics, clinical features, preoperative management, and surgical approach concerning these unusual localizations of hydatid disease. It was observed that the mesenteric localization frequently presented with acute abdominal pain (p = 0.038) and that the open approach was preferred in 85.71% of cases. Furthermore, an interdependence was identified between the localization of the cysts and the type of surgical approach (p = 0.001), with mesenteric localizations being approached through laparotomy and excision (p = 0.037), while omental localizations, due to the easier approach, benefited from laparoscopy with excision in 14.29% of cases. Overall, the laparoscopic approach was less frequently used, but its utilization resulted in a lower number of complications and faster recovery. Additionally, we present a rare case of hepatic and intra-abdominal hydatidosis, resolved exclusively through a laparoscopic approach, including a review of the literature for these uncommon localizations of hydatid disease. A 45-year-old patient diagnosed with multiple hydatid cysts, both hepatic and intraperitoneal, underwent surgical intervention with exploratory laparoscopy. Laparoscopic excision of peritoneal, epiploic, mesenteric cysts, and round ligament, along with laparoscopic inactivation, evacuation, and pericystectomy of hepatic hydatid cysts, was performed. The patient's recovery was uneventful, and she was reevaluated at 3 and 9 months without signs of recurrence. The association of hepatic hydatid cysts with multiple intra-abdominal localizations is not commonly encountered. The treatment of choice is surgical and is predominantly conducted through open surgery. The presented case is unique due to the exclusive laparoscopic approach in the management of mixed hepatic and intra-abdominal hydatidosis.

When Critical View of Safety Fails: A Practical Perspective on Difficult Laparoscopic Cholecystectomy.

The incidence of common bile duct injuries following laparoscopic cholecystectomy (LC) remains three times higher than that following open surgery despite numerous attempts to decrease intraoperative incidents by employing better training, superior surgical instruments, imaging techniques, or strategic concepts. This paper is a narrative review which discusses from a contextual point of view the need to standardise the surgical approach in difficult laparoscopic cholecystectomies, the main strategic operative concepts and techniques, complementary visualisation aids for the delineation of anatomical landmarks, and the importance of cognitive maps and algorithms in performing safer LC. Extensive research was carried out in the PubMed, Web of Science, and Elsevier databases using the terms "difficult cholecystectomy", "bile duct injuries", "safe cholecystectomy", and "laparoscopy in acute cholecystitis". The key content and findings of this research suggest there is high intersocietal variation in approaching and performing LC, in the use of visualisation aids, and in the application of safety concepts. Limited papers offer guidelines based on robust data and a timid recognition of the human factors and ergonomic concepts in improving the outcomes associated with difficult cholecystectomies. This paper highlights the most relevant recommendations for dealing with difficult laparoscopic cholecystectomies.

Therapeutic Perspectives for Microbiota Transplantation in Digestive Diseases and Neoplasia-A Literature Review.

In a mutually beneficial connection with its host, the gut microbiota affects the host's nutrition, immunity, and metabolism. An increasing number of studies have shown links between certain types of disease and gut dysbiosis or specific microorganisms. Fecal microbiota transplantation (FMT) is strongly advised for the treatment of recurrent or resistant Clostridium difficile infection (CDI) due to its outstanding clinical effectiveness against CDI. The therapeutic potential of FMT for other disorders, particularly inflammatory bowel diseases and malignancies, is currently gaining more and more attention. We summarized the most recent preclinical and clinical evidence to show the promise of FMT in the management of cancer as well as complications related to cancer treatment after reviewing the most recent research on the gut microbiota and its relationship to cancer.

Bilateral Serous Retinal Detachment as a Complication of HELLP Syndrome.

HELLP syndrome is a pregnancy complication, putting at risk the life of mother and child, characterized by high blood pressure, elevated liver enzymes and low platelets. Serous retinal detachment is a rare complication of pregnancy and may be associated with HELLP syndrome. One of the most common symptoms is a decrease in visual acuity. A rare case of bilateral exudative retinal detachment associated with HELLP syndrome is described in a 38-year-old woman a few hours after delivery. Optical coherence tomography (OCT) showed an amount of subretinal fluid and macular edema. Use of systemic corticosteroids and careful management of blood pressure led to early resolution of subretinal fluid and a good recovery of vision. Her final best corrected visual acuity was 1 (decimal notation) in both eyes at 2 weeks after delivery. These types of cases are rarely reported and highlight the importance of increasing awareness of this pathology among ophthalmologists.

Resting-state frontal, frontlateral, and parietal alpha asymmetry:A pilot study examining relations with depressive disorder type and severity.

Introduction: The search for biomarkers has been central to efforts of improving clinical diagnosis and prognosis in psychopathology in the last decades. The main approach has been to validate biomarkers that could accurately discriminate between clinical diagnoses of very prevalent forms of psychopathology. One of the most popular electrophysiological markers proposed for discrimination in depressive disorders is the electroencephalography (EEG)-derived frontal alpha asymmetry. However, the validity, reliability and predictive value of this biomarker have been questioned in recent years, mainly due to conceptual and methodological heterogeneity. Methods: In the current non-experimental, correlational study we investigated relationship of resting-state EEG alpha asymmetry from multiple sites (frontal, frontolateral, and parietal) with different forms of depressive disorders (varying in type or severity), in a clinical sample. Results: Results showed that alpha asymmetry in the parietal (P3-P4) was significantly higher than in the frontal (F3-F4) and frontolateral sites (F7-F8). However, we did not find significant relations between alpha asymmetry indices and our depressive disorder measures, except for a moderate positive association between frontolateral alpha asymmetry (eyes-closed only) and depressive disorder severity (determined through clinical structured interview). We also found no significant differences in alpha asymmetry between participants, depending on their depression type. Discussion: Based on results, we propose the parietal and frontolateral asymmetry indices to form hypotheses that should not be abandoned in the depression markers research, but worth for further experimental research. Methodological and clinical implications of the current findings are discussed.

Gut Microbiota Dysbiosis in Diabetic Retinopathy-Current Knowledge and Future Therapeutic Targets.

Diabetic retinopathy is one of the major causes of blindness today, despite important achievements in diagnosis and therapy. The involvement of a gut-retina axis is thought to be a possible risk factor for several chronic eye disease, such as glaucoma, age-related macular degeneration, uveitis, and, recently, diabetic retinopathy. Dysbiosis may cause endothelial disfunction and alter retinal metabolism. This review analyzes the evidence regarding changes in gut microbiota in patients with DR compared with diabetics and healthy controls (HCs). A systematic review was performed on PubMed, Web of Science, and Google Scholar for the following terms: "gut microbiota" OR "gut microbiome" AND "diabetic retinopathy". Ultimately, 9 articles published between 2020 and 2022 presenting comparative data on a total of 228 T2DM patients with DR, 220 patients with T2DM, and 118 HCs were analyzed. All of the studies found a distinctive microbial beta diversity in DR vs. T2DM and HC, characterized by an altered Firmicutes/Bacteroidetes ratio, a decrease in butyrate producers, and an increase in LPS-expressing and pro-inflammatory species in the Bacteroidetes and Proteobacteria phyla. The probiotic species Bifidobacterium and Lactobacillus were decreased when compared with T2DM. Gut microbiota influence retinal health in multiple ways and may represent a future therapeutic target in DR.

Cognitive and Behavioral Factors Predicting the Decision to Vaccinate against COVID-19 in Clinical Psychiatric Population-A Cross-Sectional Survey.

The spread of the COVID-19 virus created more than a medical crisis, while it also negatively affected the mental health of the general population. This context increased the vulnerability of the psychiatric population. While research interest highly targeted vaccine hesitancy and acceptance, many studies focused on trust issues-both in vaccine efficacy and in communication with authorities. Less is known about the psychological underpinnings of the COVID vaccination decision, specifically in the high-uncertainty circumstances due to the novelty of the virus. In a cross-sectional study, we investigated the predictive value of several cognitive (perceived risk, vulnerability, uncertainty, and trust in one's decision) and behavioral (previous vaccinations, social media use, and practicing preventive behavior) factors, for the vaccination decision against COVID-19, for 252 psychiatric inpatients (data collected between September 2021 and February 2022). Demographics and diagnostics were also considered. We found a significant relationship between the "Perceived risk of vaccination" and the choice of vaccination (χ2(2, N = 252) = 58.59, p ≤ 0.001), and between the "Trust in own decision to vaccinate" and the decision to vaccinate (χ2(2, N = 252) = 31,5, p ≤ 0.001). The overall regression model was statistically significant (χ2 (9, N = 252) = 97.1, p < 0.001), with between 30% and 45% of the variance in the odds of a positive decision explained by the predictor set. The model coefficients analysis showed that an individual with a psychiatric disorder but with higher confidence in their decision had significant (p < 0.001) increased odds of the decision to vaccinate against COVID-19 by 893%. A former voluntary vaccination did not significantly associate with the decision to vaccinate against COVID-19 (χ2(1, N = 252) = 2.74, p > 0.05) in this special population. No other behavioral factors, diagnosis, or demographics were significant as predictors, for the clinical psychiatric population surveyed, except the educational level. Implications for future vaccination acceptance of this special population are discussed.

Risk assessment of amputation in patients with diabetic foot.

The prevalence of diabetes has increased dramatically over the past decade, especially in developing countries, reaching pandemic proportions. Although has been the most important factor influencing the prevalence of type 2 diabetes, the prevalence of type 2 diabetes is on the increase among younger adults. The subsequent rate of increase with age is variable, which is more evident in societies where the general prevalence of the disease is higher. Based on clinical and statistical data obtained from the patients who were admitted to The First and Second Surgery Wards in the Sibiu County Emergency University Clinical Hospital (Sibiu, Romania) and the Proctoven Clinic (Sibiu, Romania) between January 2018 and December 2020, the present study attempted to devise a risk score that can be applied for the benefit of patients. The ultimate aim was that this risk score may be eventually applied by diabetologists and surgeons to assess the risk of amputation in patients with diabetic foot lesions. An important part in the therapeutic management of diabetic foot injuries is the assessment of risk factors. Using this risk score system devised, the risk factors that were found to exert influence in aggravating diabetic foot injuries are smoking, obesity, dyslipidaemia, unbalanced diabetes mellitus (glycated haemoglobin ≥7.5%), duration of diabetes >5 years, hepatic steatosis and the co-existence of various heart diseases. To conclude, all these risk factors aforementioned can decrease the effectiveness of treatment and can have a significant impact on the quality of life, if they are not well known.

Failure in Medical Practice: Human Error, System Failure, or Case Severity?

The success rate in medical practice will probably never reach 100%. Success rates depend on many factors. Defining the success rate is both a technical and a philosophical issue. In opposition to the concept of success, medical failure should also be discussed. Its causality is multifactorial and extremely complex. Its actual rate and its real impact are unknown. In medical practice, failure depends not only on the human factor but also on the medical system and has at its center a very important variable-the patient. To combat errors, capturing, tracking, and analyzing them at an institutional level are important. Barriers such as the fear of consequences or a specific work climate or culture can affect this process. Although important data regarding medical errors and their consequences can be extracted by analyzing patient outcomes or using quality indicators, patient stories (clinical cases) seem to have the greatest impact on our subconscious as medical doctors and nurses and these may generate the corresponding and necessary reactions. Every clinical case has its own story. In this study, three different cases are presented to illustrate how human error, the limits of the system, and the particularities of the patient's condition (severity of the disease), alone or in combination, may lead to tragic outcomes There is a need to talk openly and in a balanced way about failure, regardless of its cause, to look at things as they are, without hiding the inconvenient truth. The common goal is not to find culprits but to find solutions and create a culture of safety.

Optimal Timing and Outcomes of Minimally Invasive Approach in Acute Biliary Pancreatitis.

BACKGROUND We analyzed the outcomes of early biliary decompression by a minimally invasive approach in acute biliary pancreatitis (ABP). MATERIAL AND METHODS A retrospective study was conducted on 143 patients with ABP who underwent biliary decompression by laparoscopic or endoscopic approach between January 2015 and March 2022. Data from the observation sheets and surgical protocols were analyzed in terms of demographic characteristics, clinical and paraclinical features at admission, comorbidities, therapeutic management, and outcomes. RESULTS The mean patient age was 62.3±11.4 years. Mild ABP had a higher frequency in men (75.5%) and urban areas (70.4%). The comorbidities associated with a higher risk of severe forms were diabetes mellitus (odds ratio [OR]: 11.250), chronic bronchopneumopathy (OR: 29.297), and ischemic coronary disease (OR: 2.784). The mean hospital stay was 7.6±3.8 days and was significantly higher in severe forms (10±2.4 days, P<0.001). The time from onset to presentation was significantly higher in severe vs mild forms (5.6 vs 1.8 days, P<0.001) and was associated with systemic and local complications. Creatinine over 2 mg/dL (OR: 4.821) and leukocytes >15 000/mmc at admission (OR: 3.533) were risk factors for systemic complications, while obesity was associated with increased local complications (OR: 5.179). None of the patients with an early presentation developed severe ABP. CONCLUSIONS Early biliary decompression, as soon as possible after onset, either by an endoscopic or minimally invasive approach, is a safe and effective procedure in ABP. The type of procedure and optimal timing should be individualized, according to the patient's local and general features.

A Rare Case of Polysplenia Syndrome Associated with Severe Cardiac Malformations and Congenital Alveolar Dysplasia in a One-Month-Old Infant: A Complete Macroscopic and Histopathologic Study.

Polysplenia syndrome represents a type of left atrial isomerism characterized by multiple small spleens, often associated with cardiac malformations and with situs ambiguus of the abdominal organs. The case presented is of a one-month-old male infant, weighing approximately 3000 g, born at the County Clinical Emergency Hospital of Sibiu, who was hospitalized from birth until death. The patient suffered cardio-respiratory arrest due to severe hypoxia and septicemia on the background of a series of complex cardiac malformations associated with congenital abdominal organ anomalies. Examination of the body revealed a common atrium with complete atrioventricular canal defect, left ventricular hypertrophy, right ventricle hypoplasia, truncus arteriosus, superior vena cava duplication, bilobation of the lungs, situs ambiguous of the abdominal organs with right-sided stomach, a midline liver, gall bladder agenesis, multiple right-sided spleens and complete inversion of the intestines and pancreas. Histopathology concluded that the patient suffered cardiac lesions consistent with infantile lactic acidosis, as well as pulmonary modifications suggesting congenital alveolar dysplasia and altered hepatic architecture compatible with fibrosis.

Serum levels of copper and zinc in diabetic retinopathy: Potential new therapeutic targets (Review).

Diabetic retinopathy (DR) is a microvascular disorder occurring due to the long-term effects of diabetes, leading to vision-threatening damage to the retina. The human body has an elaborate system for managing and regulating the number of key trace metals circulating in the blood and stored cells. Inadequate zinc (Zn) and concurrent excess of copper (Cu) levels are associated with an increased level of oxidative stress, which may aggravate the microvascular lesions in diabetes mellitus. Several studies have revealed a significantly lower serum Zn concentration and increased Cu levels in DR when compared with diabetic patients without retinopathy and normal controls. These abnormalities are correlated with the duration of diabetes and higher levels of HbA1C. Multiple pathological mechanisms are proposed to explain these changes including hyperzincuria associated with polyuria, glycosuria, and proteinuria in diabetic patients, as well as impaired absorption of Zn at the gastrointestinal level. Increased levels of free Cu ions may be attributed to glycation and the release of Cu ions from the Cu-binding sites of proteins. Zn supplements and selective Cu chelators may be useful to alleviate oxidative stress and prevent DR progression.

Ocular Side Effects of Aromatase Inhibitor Endocrine Therapy in Breast Cancer - A Review.

BACKGROUND: Aromatase inhibitor therapy is currently the preferred choice in postmenopausal women with estrogen receptor positive breast cancer. This article reviews the ocular side effects of treatment with aromatase inhibitors (AIs) in patients with breast cancer. MATERIALS AND METHODS: A comprehensive search was performed on PubMed, Web of Science and Google scholar. RESULTS: After duplication removal, 14 clinical studies and 5 case reports, published between 2008 and 2021, were identified. Most frequently, AI treatment resulted in minor to moderate dry eye symptoms. "De novo" onset of Sjogren syndrome during AI therapy was also reported. Retinal and optic nerve side effects varied from mild, subclinical anatomic and functional impairment to severe decreased vision, secondary to hemi-central retinal artery occlusion, bilateral optic neuritis or uveitis with bilateral macular edema. CONCLUSION: Visual disturbances encountered during AI treatment may be underestimated. Ophthalmic screening is important for early detection and appropriate treatment.

Systematic review of the role of indocyanine green near-infrared fluorescence in safe laparoscopic cholecystectomy (Review).

With the widespread introduction of laparoscopic cholecystectomy, the incidence of iatrogenic main bile duct lesions has significantly increased, with incidences ranging from 0.2 to 1.5% according to current studies. Although there are studies regarding the use of indocyanine green (ICG) for improved visualization of the biliary anatomy, there is no consensus on the dose, timing and optimal mode of administration, or the indications in which ICG provides a real benefit through increased safety in laparoscopic cholecystectomy (LC). A systematic review was performed on articles in English published until March 2021, which were identified on PubMed, Springer Nature, Elsevier and Scopus via specific mesh terms: 'Indocyanine green'/'near-infrared fluorescence' and 'laparoscopic cholecystitis'. The most used method of administration of ICG was intravenously, only one study evaluated the efficiency of a near-infrared cholangiogram (NIRC) when ICG was administered directly in the gallbladder. The majority of the studies included in the review used 2.5 mg of ICG administered within 1 h before imaging. The intensity of the NIRC fluorescence signal was revealed to depend on several factors, with obesity and inflammation as the most clinically significant. NIRC was reported to be a simple, feasible, safe and cost-effective procedure, which may improve safety in difficult cases of LC. NIRC use in combination with white light has been demonstrated to be superior to white light alone in identifying extrahepatic biliary anatomy, thus decreasing the risk of intraoperative bile duct injuries (BDI). For its large-scale use, data on a higher number of patients to confirm its clinical value and specific indications is required.

Impact of modern personalized treatment of breast cancer on surgical attitude and outcomes.

Multimodal treatment of breast cancer has made steady progress in recent years. The involvement of modern oncology, diagnostic imaging techniques and surgical treatment, have brought a definite benefit to patients, defining the multidisciplinary treatment of breast cancer. The introduction of immunohistochemical testing and genetic screening has led to the prioritization of therapy according to their results and a correct approach to initiating treatment. The main aim of the present study was to conduct a comparative analysis through a retrospective study of the therapeutic means used in breast cancer with the statistical evaluation of the obtained results. To carry out the study, a group of 125 patients hospitalized during the period January 2015 to December 2020, were included, and the parameters were selected from the observation sheets. The results of the study demonstrated the superiority of multimodal treatment of breast cancer over surgical treatment as the only therapeutic management. The introduction of ultrasound-guided biopsies and conservative surgical options has led to increased diagnostic accuracy and a significant improvement in aesthetic outcome. The multidisciplinary approach to breast cancer allows an individualized treatment by performing immunohistochemical testing and through the use of neoadjuvant and adjuvant treatment combined with conservative surgical techniques with a more favorable cosmetic and oncological result, with reduced postoperative complications.

Tyrosine kinase inhibitors in breast cancer (Review).

Anti-epidermal growth factor receptor (EGFR)-targeted therapy has been intensely researched in the last years, motivated by the favorable results obtained with monoclonal antibodies in HER2-enriched breast cancer (BC) patients. Most researched alternatives of anti-EGFR agents were tyrosine kinase inhibitors (TKIs) and monoclonal antibodies. However, excluding monoclonal antibodies trastuzumab and pertuzumab, the remaining anti-EGFR molecules have exhibited disappointing results, due to the lack of specificity and frequent adverse side effects. TKIs have several advantages, including reduced cardiotoxicity, oral administration and favorable penetration of blood-brain barrier for brain metastatic BC. Lapatinib and neratinib and recently pyrotinib (approved only in China) are the only TKIs from dozens of molecules researched over the years that were approved to be used in clinical practice with limited indications, in a subset of BC patients, single or in combination with other chemotherapy or hormonal therapeutic agents. Improved identification of BC subtypes and improved characterization of aggressive forms (triple negative BC or inflammatory BC) should lead to advancements in shaping of targeted agents to improve the outcome of patients.