Postoperative assessment of malignant melanoma aggressiveness for further treatment personalization

The aim of the study was to develop, implement and evaluate a method for predicting the aggressiveness of primary melanoma after surgical removal.It was established that the method for predicting tumor aggressiveness allows to determine the degree of aggressiveness, life expectancy, and to identify patients with poor prognosis in order to individualize treatment. The survival rate of patients was found to depend on the degree of aggressiveness of the tumor. A group of patients with stages 0-IIa (16,4 %) and tumor aggressiveness Grade II was identified as having a potentially high risk of progression, which can help individualize treatment for this category of patients. Using the method for predicting disease progression may potentially expand the scope of indications for further personalized treatment.

Treatment Options for Elderly/Unfit Patients with Chronic Lymphocytic Leukemia in the Era of Targeted Drugs: A Comprehensive Review

Chronic lymphocytic leukemia (CLL) incidence increases with age reaching 37.9/100,000 in patients over 85 years. Although there is no standardized geriatric tool specifically validated for CLL, a correct framing of the fitness status is of critical importance to individualize treatment strategies. Based on the evidence available to date, frontline chemoimmunotherapy has an increasingly narrowing application, being eligible for candidacy only in elderly fit patients without or with minimal geriatric syndromes. On the other hand, treatment with BCR inhibitors, monotherapy, or in combination with anti-CD20 antibodies (e.g., obinutuzumab), must be preferred both for frontline and relapsed CLL not only in unfit patients, but also in fit patients with unmutated IGHV or harboring del(17p) and/or TP53 mutations/deletions. Second-generation inhibitors (e.g., acalabrutinib, zanubrutinib, pirtobrutinib) are novel compounds that, due to their better safety profile and different specificity, will help physicians overcome some of the safety issues and treatment resistances. In the era of targeted therapies, treatment decisions in elderly and/or unfit patients with CLL must be a balance between efficacy and safety, carefully evaluating comorbidities and geriatric syndromes to ensure the best approach to improve both quality of life and life expectancy.

Validation of the Dutch Eating Behavior Questionnaire in a Romanian Adult Population

(1) Background: Obesity, part of the triple global burden of disease, is increasingly attracting research on its preventive and curative management. Knowledge of eating behavior can be useful both at the individual level (to individualize treatment for obesity) and the population level (to implement more suitable food policies). The Dutch Eating Behavior Questionnaire (DEBQ) is a widely used international tool to assess eating behavior, i.e., emotional, external and restricted eating styles. The aim of this study was to validate the Romanian version of DEBQ, as obesity is a major concern in Romania. (2) Methods: Our study tested the psychometric properties of the Romanian version of DEBQ on an adult population and explored the associations of eating behavior with weight status (3) Results: The study showed a factor load similar to the original version of the questionnaire and a very good internal validity (Cronbach’s alpha fidelity coefficient greater than 0.8 for all scales of the questionnaire) for the Romanian version of DEBQ and showed that all of the scales positively correlated with body mass index in both men and women. (4) Conclusions: This study will enable the use of the DEBQ Romanian version on the adult population of Romania where the findings could be incorporated into developing better strategies to reduce the burden of nutrition-related diseases.

Risk Scores and Machine Learning to Identify Patients With Acute Periprosthetic Joints Infections That Will Likely Fail Classical Irrigation and Debridement

The most preferred treatment for acute periprosthetic joint infection (PJI) is surgical debridement, antibiotics and retention of the implant (DAIR). The reported success of DAIR varies greatly and depends on a complex interplay of several host-related factors, duration of symptoms, the microorganism(s) causing the infection, its susceptibility to antibiotics and many others. Thus, there is a great clinical need to predict failure of the “classical” DAIR procedure so that this surgical option is offered to those most likely to succeed, but also to identify those patients who may benefit from more intensified antibiotic treatment regimens or new and innovative treatment strategies. In this review article, the current recommendations for DAIR will be discussed, a summary of independent risk factors for DAIR failure will be provided and the advantages and limitations of the clinical use of preoperative risk scores in early acute (post-surgical) and late acute (hematogenous) PJIs will be presented. In addition, the potential of implementing machine learning (artificial intelligence) in identifying patients who are at highest risk for failure of DAIR will be addressed. The ultimate goal is to maximally tailor and individualize treatment strategies and to avoid treatment generalization.

Monitored Exercise and Oxygen Therapy Improves Aerobic and Autonomic Function in Post-Acute Sequelae of SARS-CoV-2 Infection (PASC): A Case Series

Case Description: Three females (ages 34, 38, and 38) who contracted COVID-19 in March or April 2020 were treated for post-acute sequelae of SARS-CoV-2 infection (PASC) associated cardiopulmonary and autonomic dysfunction seven to eight months following acute-illness. Exercise tolerance was tested using the Bensen protocol, followed by 22 treatment sessions of graduated treadmill exercise combined with supplemental oxygen two or three times a week, after which the exercise tolerance test was repeated. All patients demonstrated improvement in autonomic function and heart rate response during exercise and demonstrated ~54% improvement in exercise tolerance. Dyspnea remitted or improved in all patients, as did other PASC symptoms, including cough, dyspnea, larynx inflammation, chest tightness, fatigue, and post-exertional malaise. Discussion: It appears that PASC is a multisystemic, inflammation-mediated condition, that affects the respiratory, cardiac, neurologic, gastrointestinal and autonomic nervous systems, with high variability in symptomatology and course, both between patients and within individuals. Patient safety should be maximized by conducting thorough cardiac, respiratory, neurologic and pre-rehabilitation evaluations to rule out potential complications related to activity and exercise. Clinical course and comprehensive monitoring of heart rate and rhythm, blood pressure, and oxygen saturation should be evaluated before exercise time and intensity is increased, very conservatively.Summary: Due to the variable nature of PASC, it is crucial to individualize treatment protocols and to modify the protocol based on patient response; however, we show that gradual, monitored exercise combined with supplemental oxygen may improve lingering symptoms and autonomic function in some PASC patients.

Clinical Application of AMH Measurement in Assisted Reproduction

Anti-Müllerian hormone reflects the continuum of the functional ovarian reserve, and as such can predict ovarian response to gonadotropin stimulation and be used to individualize treatment pathways to improve efficacy and safety. However, consistent with other biomarkers and age-based prediction models it has limited ability to predict live birth and should not be used to refuse treatment, but rather to inform counselling and shared decision making. The use of absolute clinical thresholds to stratify patient phenotypes, assess discordance and individualize treatment protocols in non-validated algorithms combined with the lack of standardization of assays may result in inappropriate classification and sub-optimal clinical decision making. We propose that holistic baseline phenotyping, incorporating antral follicle count and other patient characteristics is critical. Treatment decisions driven by validated algorithms that use ovarian reserve biomarkers as continuous measures, reducing the risk of misclassification, are likely to improve overall outcomes for our patients.

How do I sequence therapy for follicular lymphoma?

In the past decade, many new agents have been introduced for the management of follicular lymphoma, and therapeutic strategies have evolved over time. The clinical benefits of the different treatments vary and, at the time of progression, are influenced by patient and disease characteristics, the duration of the interval from last treatment, and the nature of the treatments previously administered. Altogether, this results in a marked heterogeneity of clinical situations encountered during the treatment of these patients. Despite numerous trials performed in the field, there is no single standard of care for patients undergoing second-line treatment or beyond. Furthermore, patients recruited in these studies have characteristics that rarely represent the full spectrum of possible clinical presentations. Therefore, to optimally individualize treatment, all of the risks (short- and long-term) and benefits of the available options should be well known. Discussing the goals of therapy with the patient at each intervention is also critical in providing an optimal sequence of therapy.

Survival in Patients With Brain Metastases: Summary Report on the Updated Diagnosis-Specific Graded Prognostic Assessment and Definition of the Eligibility Quotient

PURPOSE Conventional wisdom has rendered patients with brain metastases ineligible for clinical trials for fear that poor survival could mask the benefit of otherwise promising treatments. Our group previously published the diagnosis-specific Graded Prognostic Assessment (GPA). Updates with larger contemporary cohorts using molecular markers and newly identified prognostic factors have been published. The purposes of this work are to present all the updated indices in a single report to guide treatment choice, stratify research, and define an eligibility quotient to expand eligibility. METHODS A multi-institutional database of 6,984 patients with newly diagnosed brain metastases underwent multivariable analyses of prognostic factors and treatments associated with survival for each primary site. Significant factors were used to define the updated GPA. GPAs of 4.0 and 0.0 correlate with the best and worst prognoses, respectively. RESULTS Significant prognostic factors varied by diagnosis and new prognostic factors were identified. Those factors were incorporated into the updated GPA with robust separation ( P < .01) between subgroups. Survival has improved, but varies widely by GPA for patients with non–small-cell lung, breast, melanoma, GI, and renal cancer with brain metastases from 7-47 months, 3-36 months, 5-34 months, 3-17 months, and 4-35 months, respectively. CONCLUSION Median survival varies widely and our ability to estimate survival for patients with brain metastases has improved. The updated GPA (available free at brainmetgpa.com) provides an accurate tool with which to estimate survival, individualize treatment, and stratify clinical trials. Instead of excluding patients with brain metastases, enrollment should be encouraged and those trials should be stratified by the GPA to ensure those trials make appropriate comparisons. Furthermore, we recommend the expansion of eligibility to allow for the enrollment of patients with previously treated brain metastases who have a 50% or greater probability of an additional year of survival (eligibility quotient > 0.50).

The Perils of Haemorrhoids Treatment

Treating problematic haemorrhoids has taken a long turmoil route. Its peak incidence is among 45 to 65 years of age group. Typically, problematic haemorrhoids present in multi-symptoms forms like a prolapsed lump, painless bleeding, discomfort, soiling, or itchiness. Many theories were postulated in the pathophysiology of symptomatic haemorrhoids. The sliding and engorged of anal cushion with hypervascularity is the most popular. This is an updated review of published English-language literature regarding the treatment of haemorrhoids. The treatment includes medical therapy, office procedures, and surgical operations. Merits and demerits of the different modalities of treatment of haemorrhoids are presented. The best treatment options are difficult to ascertain. It should be tailored to individualize treatment according to their presentation and severity. Up till recently, the excisional haemorrhoidectomies are considered the standard procedure for haemorrhoid treatment. These techniques produce significant post-operative pain to the patient, which hinders them from normal daily activity. Recent advancement in surgical intervention has focused on minimising severity of pain and enhances recovery.

Monogenic Diabetes: Genetics and Relevance on Diabetes Mellitus Personalized Medicine

Background: Diabetes mellitus (DM) is a complex disease with significant impression in today's world. Aside from the most common types recognized over the years, such as type 1 diabetes (T1DM) and type 2 diabetes (T2DM), recent studies have emphasized the crucial role of genetics in DM, allowing the distinction of monogenic diabetes. Methods: Authors did a literature search with the purpose of highlighting and clarifying the subtypes of monogenic diabetes, as well as the accredited genetic entities responsible for such phenotypes. Results: The following subtypes were included in this literature review: maturity-onset diabetes of the young (MODY), neonatal diabetes mellitus (NDM) and maternally inherited diabetes and deafness (MIDD). So far, 14 subtypes of MODY have been identified, while three subtypes have been identified in NDM - transient, permanent, and syndromic. Discussion: Despite being estimated to affect approximately 2% of all the T2DM patients in Europe, the exact prevalence of MODY is still unknown, accentuating the need for research focused on biomarkers. Consequently, due to its impact in the course of treatment, follow-up of associated complications, and genetic implications for siblings and offspring of affected individuals, it is imperative to diagnose the monogenic forms of DM accurately. Conclusion: Currently, advances in the genetics field allowed the recognition of new DM subtypes, which until now, were considered slight variations of the typical forms. Thus, it is imperative to act in the close interaction between genetics and clinical manifestations, to facilitate diagnosis and individualize treatment.