Diseases, Volume 12, Issue 4 (April 2024) – 16 articles

This systematic review critically evaluates the impact of systemic treatments on outcomes and quality of life (QoL) in patients with RAS-positive stage IV colorectal cancer, with studies published up to December 2023 across PubMed, Scopus, and Web of Science. From an initial pool of 1345 articles, 11 relevant studies were selected for inclusion, encompassing a diverse range of systemic treatments, including panitumumab combined with FOLFOX4 and FOLFIRI, irinotecan paired with panitumumab, regorafenib followed by cetuximab ± irinotecan and vice versa, and panitumumab as a maintenance therapy post-induction. Patient demographics predominantly included middle-aged to elderly individuals, with a slight male predominance. Racial composition, where reported, showed a majority of Caucasian participants, highlighting the need for broader demographic inclusivity in future research. Key findings revealed that the addition of panitumumab to chemotherapy (FOLFOX4 or FOLFIRI) did not significantly compromise QoL while notably improving disease-free survival, with baseline EQ-5D HSI mean scores ranging from 0.76 to 0.78 and VAS mean scores from 70.1 to 74.1. Improvements in FACT-C scores and EQ-5D Index scores particularly favored panitumumab plus best supportive care in KRAS wild-type mCRC, with early dropout rates of 38–42% for panitumumab + BSC. Notably, cetuximab + FOLFIRI was associated with a median survival of 25.7 months versus 16.4 months for FOLFIRI alone, emphasizing the potential benefits of integrating targeted therapies with chemotherapy. In conclusion, the review underscores the significant impact of systemic treatments, particularly targeted therapies and their combinations with chemotherapy, on survival outcomes and QoL in patients with RAS-positive stage IV colorectal cancer, and the need for personalized treatment. Full article

Gastric cancer ranks as the fifth most common cancer, and the assessment of inflammatory biomarkers in these patients holds significant promise in predicting prognosis. Therefore, data from patients undergoing surgical intervention for gastric cancer over a 7-year period were analyzed. This study was retrospective and involved a preoperative investigation of six inflammatory parameters derived from complete blood counts. Statistical analysis revealed a significant increase in the leucocyte-to-monocyte ratio (LMR) (p = 0.048), along with a significant decrease in the number of lymphocytes and monocytes compared to patients with successful discharge. Taking into consideration patients undergoing emergency surgery, a significant increase in the LMR (p = 0.009), neutrophil-to-lymphocyte ratio (NLR) (p = 0.004), Aggregate Index of Systemic Inflammation (AISI) (p = 0.01), and Systemic Immune-Inflammation Index (SII) (p = 0.028) was observed. Regarding relapse, these patients exhibited significant increases in AISI (p = 0.032) and SII (p = 0.047). Inflammatory biomarkers represent a valuable tool in evaluating and predicting the prognosis of patients with gastric cancer. Full article

Advanced and metastatic cervical cancer remains a formidable challenge in oncology, with immune checkpoint inhibitors such as the PD-1 inhibitor nivolumab emerging as a potential therapeutic option. This systematic review rigorously assesses the effectiveness and outcomes of various nivolumab treatment regimens within this patient cohort, drawing from clinical trials and real-world evidence up to December 2023. Following a comprehensive search across PubMed, Scopus, and Embase, four studies were deemed eligible, involving a collective total of 80 patients. One preliminary trial data were excluded from the final analysis, as well as four other proceedings and abstracts on the efficacy and safety of nivolumab on advanced cervical cancer. The patients’ average age across these studies was 48 years, with an average of 38% having an Eastern Cooperative Oncology Group (ECOG) performance status of 1. Notably, 64% of all patients were positive for high-risk HPV, and 71% exhibited PD-L1 positivity, indicating a substantial target population for nivolumab. The analysis revealed a pooled objective response rate (ORR) of 48%, with a disease control rate (DCR) averaging 71%. Moreover, progression-free survival (PFS) at 6 months was observed at an average rate of 50%, reflecting the significant potential of nivolumab in managing advanced stages of the disease. The review highlights the influence of PD-L1 status on response rates and underscores the enhanced outcomes associated with combination therapy approaches. By delineating the variability in treatment efficacy and pinpointing key factors affecting therapeutic response and survival, this systematic review calls for further investigations to refine nivolumab’s clinical application, aiming to improve patient outcomes in advanced and metastatic cervical cancer. Full article

Congenital aniridia is a rare bilateral ocular malformation characterized by the partial or complete absence of the iris and is frequently associated with various anomalies, including keratopathy, cataract, glaucoma, and foveal and optic nerve hypoplasia. Additionally, nearly 50% of individuals with congenital aniridia experience symptoms of ocular dryness. Traditional treatment encompasses artificial tears and autologous serum. This study aimed to assess the effectiveness and safety of using platelet rich in growth factors (PRGF) plasma in patients with congenital aniridia and ocular dryness symptoms. Methods: The included patients underwent two cycles of a 3-month PRGF treatment. At 6 months, symptomatology was evaluated using the OSDI and SANDE questionnaires, and ocular surface parameters were analyzed. Results: The OSDI and SANDE values for frequency and severity demonstrated statistically significant improvements (p < 0.05). Ocular redness, corneal damage (corneal staining), and tear volume (Schirmer test) also exhibited statistically significant improvements (p < 0.05). No significant changes were observed in visual acuity or in the grade of meibomian gland loss. Conclusion: The use of PRGF in patients with congenital aniridia and ocular dryness symptoms led to significant improvements in symptomatology, ocular redness, and ocular damage. No adverse effects were observed during the use of PRGF. Full article

Background: Plastic surgery is one of the medical specialties with the highest risk of recurrent medical malpractice claims. The frequency of civil lawsuits represents an issue for the micro- and macro-economy of practitioners of these health treatments. This paper aims to discuss the medico-legal aspects and claim path in a case of a cosmetic blepharoplasty complicated by lagophthalmos wrongly related to the procedure but due to missed hyperthyroidism. Case Description and Literature Review: A 48-year-old woman who underwent cosmetic blepharoplasty with undiagnosed hyperthyroidism claimed that the lagophthalmos that occurred some months after the procedure was due to medical malpractice, due to an over-resection of the exuberant lower eyelid tissue. The review question was, “Are thyroid disfunctions usually considered contraindications to be communicated to patients who undergo blepharoplasty?”, and the databases MEDLINE via PubMed, Embase, Scopus, Ovid, ISI Web of Science, Cochrane, and Google Scholar were used. Results and Discussion: There were 21 eligible papers. The case highlights the importance and complexity of causal inference (such as unknown thyroid dysfunctions), related informed consent involving information on possible complications unrelated to malpractice, and guidelines recommending endocrinological consultation for cosmetic/functional blepharoplasty in patients at risk (e.g., female patients with a known history of thyroid disease). Full article

Since the inception of the SARS-CoV-2 pandemic, healthcare systems around the world observed an increased rate of Acute Limb Ischemia (ALI) in patients with a COVID-19 infection. Despite several pieces of evidence suggesting that COVID-19 infection may also worsen the prognosis associated with ALI, only a small number of published studies include a direct comparison regarding the outcomes of both COVID-19 and non-COVID-19 ALI patients. Based on the above, a systematic review and a meta-analysis of the literature were conducted, evaluating differences in the incidence of two major outcomes (amputation and mortality rate) between patients concurrently affected by COVID-19 and negative ALI subjects. PubMed (MEDLINE), Web of Science, and Embase (OVID) databases were scrutinized from January 2020 up to 31 December 2023, and 7906 total articles were recovered. In total, 11 studies (n: 15,803 subjects) were included in the systematic review, and 10 of them (15,305 patients) were also included in the meta-analysis. Across all the studies, COVID-19-positive ALI patients experienced worse outcomes (mortality rates ranging from 6.7% to 47.2%; amputation rates ranging from 7.0% to 39.1%) compared to non-infected ALI patients (mortality rates ranging from 3.1% to 16.7%; amputation rates ranging from 2.7% to 18%). Similarly, our meta-analysis shows that both the amputation rate (OR: 2.31; 95% CI: 1.68–3.17; p < 0.00001) and mortality (OR: 3.64; 95% CI: 3.02–4.39; p < 0.00001) is significantly higher in COVID-19 ALI patients compared to ALI patients. Full article

The impact of outbreak response immunization (ORI) can be estimated by comparing observed outcomes to modelled counterfactual scenarios without ORI, but the most appropriate metrics depend on stakeholder needs and data availability. This study developed a framework for using mathematical models to assess the impact of ORI for vaccine-preventable diseases. Framework development involved (1) the assessment of impact metrics based on stakeholder interviews and literature reviews determining data availability and capacity to capture as model outcomes; (2) mapping investment in ORI elements to model parameters to define scenarios; (3) developing a system for engaging stakeholders and formulating model questions, performing analyses, and interpreting results; and (4) example applications for different settings and pathogens. The metrics identified as most useful were health impacts, economic impacts, and the risk of severe outbreaks. Scenario categories included investment in the response scale, response speed, and vaccine targeting. The framework defines four phases: (1) problem framing and data sourcing (identification of stakeholder needs, metrics, and scenarios); (2) model choice; (3) model implementation; and (4) interpretation and communication. The use of the framework is demonstrated by application to two outbreaks, measles in Papua New Guinea and Ebola in the Democratic Republic of the Congo. The framework is a systematic way to engage with stakeholders and ensure that an analysis is fit for purpose, makes the best use of available data, and uses suitable modelling methodology. Full article

Globally, sepsis and pneumonia account for significant mortality and morbidity. A complex interplay of immune-molecular pathways underlies both sepsis and pneumonia, resulting in similar and overlapping disease characteristics. Sepsis could result from unmanaged pneumonia. Similarly, sepsis patients have pneumonia as a common complication in the intensive care unit. A significant percentage of pneumonia is misdiagnosed as septic shock. Therefore, our knowledge of the clinical relationship between pneumonia and sepsis is imperative to the proper management of these syndromes. Regarding pathogenesis and etiology, pneumococcus is one of the leading pathogens implicated in both pneumonia and sepsis syndromes. Growing evidence suggests that pneumococcal pneumonia can potentially disseminate and consequently induce systemic inflammation and severe sepsis. Streptococcus pneumoniae could potentially exploit the function of dendritic cells (DCs) to facilitate bacterial dissemination. This highlights the importance of pathogen-immune cell crosstalk in the pathophysiology of sepsis and pneumonia. The role of DCs in pneumococcal infections and sepsis is not well understood. Therefore, studying the immunologic crosstalk between pneumococcus and host immune mediators is crucial to elucidating the pathophysiology of pneumonia-induced lung injury and sepsis. This knowledge would help mitigate clinical diagnosis and management challenges. Full article

Sarcopenia is a systemic skeletal muscle disease that is more prevalent in older adults. The role of exercise in improving the disease has been demonstrated. However, due to the variety of exercise modalities, it is not clear what type of exercise provides the best benefit. The aim of this meta-analysis was to analyze the effects of different exercise modalities on grip strength, appendicular skeletal muscle index, skeletal muscle index, and knee extensor strength in elderly patients with sarcopenia. The protocol for this evaluation was registered on the PROSPERO website and the databases PubMed, WOS, Cochrane Library, and Embase were searched. Thirteen studies were included in the analysis. The results showed that exercise interventions had positive effects on grip strength and knee extension muscle strength, with resistance training being the most effective. There was no significant improvement in appendicular skeletal muscle index or skeletal muscle index. This study still has limitations. For example, age group and exercise duration were not considered. Future studies should further explore benefits in age groups as well as other relevant outcome indicators. Full article

ADHD is a neurodevelopmental disorder that children and adults can develop. A complex interplay of genetic and environmental factors may underlie interindividual variability in ADHD and potentially related aggressive behavior. Using high-resolution molecular biology techniques, we investigated the impact of some MAOA and SLC6A4 variations on ADHD and aggressive behavior in a group of 80 Italian children with ADHD and in 80 healthy controls. We found that homozygous genotypes of MAOA rs6323 and rs1137070 were associated with an increased risk of ADHD (p = 0.02 and p = 0.03, respectively), whereas the heterozygous genotypes (GT of rs6323 and CT of rs1137030) (p = 0.0002 and p = 0.0006) were strongly linked to a lower risk of developing this disorder. In patients with aggressive behavior, we highlighted only a weak negative association of both MAOA polymorphisms (heterozygous genotypes) with aggressiveness, suggesting that these genotypes may be protective towards specific changes in behavior (p = 0.05). Interestingly, an increase in the GG genotype of rs6323 (p = 0.01) and a decrease in GT genotype (p = 0.0005) was also found in patients without aggressive behavior compared to controls. Regarding 5HTT gene genotyping, no allele and genotype differences have been detected among patients and controls. Our work shows that defining a genetic profile of ADHD may help in the early detection of patients who are more vulnerable to ADHD and/or antisocial and aggressive behavior and to design precision-targeted therapies. Full article

Alcoholic liver disease (ALD) is a major cause of chronic liver disease. This term covers a broad spectrum of liver lesions, from simple steatosis to alcoholic hepatitis and cirrhosis. The pathogenesis of ALD is multifactorial and not fully elucidated due to complex mechanisms related to direct ethanol toxicity with subsequent hepatic and systemic inflammation. The accumulation of pro-inflammatory cytokines and the reduction of anti-inflammatory cytokines promote the development and progression of ALD. To date, there are no targeted therapies to counter the progression of chronic alcohol-related liver disease and prevent acute liver failure. Corticosteroids reduce mortality by acting on the hepatic-systemic inflammation. On the other hand, several studies analyzed the effect of inhibiting pro-inflammatory cytokines and stimulating anti-inflammatory cytokines as potential therapeutic targets in ALD. This narrative review aims to clarify the role of the main cytokines involved in the pathogenesis and treatment of ALD. Full article

Children with Down Syndrome (DS) frequently undergo health challenges, including a higher prevalence of overweight and obesity. We aimed to evaluate the impact of dietary and physical advice provided by a specialized pediatrician over two years. In this prospective study, 44 children with DS, aged 2 to 17, underwent outpatient follow-up visits every six months between December 2020 and May 2023. Dietary habits, physical activities, anthropometric data, and laboratory results were recorded at baseline and 2-year follow-up. Adherence to the Mediterranean diet and physical activity were investigated using the ‘KIDMED’ and ‘Godin–Shepard Leisure-Time’ questionnaires, respectively, completed by the parents of the children. Venous blood samples were taken to determine the lipid profile. A significant reduction in BMI z-scores (p = 0.006) and an improvement in Godin–Shepard questionnaire scores (p = 0.0004) were observed. On the other hand, the lipid profile worsened, with an increase in LDL-c (p = 0.04) and a decrease in HDL-c (p = 0.03). Children with DS may benefit from an educational program on nutrition and physical activity to optimize weight control. Different interventions should target the lipid profile. Preventive intervention and follow-up by the pediatrician are essential for DS, which should continue into adulthood. Full article

The circulating severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variant presents an ongoing challenge for surveillance and detection. It is important to establish an assay for SARS-CoV-2 antibodies in vaccinated individuals. Numerous studies have demonstrated that binding antibodies (such as S-IgG and N-IgG) and neutralizing antibodies (Nabs) can be detected in vaccinated individuals. However, it is still unclear how to evaluate the consistency and correlation between binding antibodies and Nabs induced by inactivated SARS-CoV-2 vaccines. In this study, serum samples from humans, rhesus macaques, and hamsters immunized with inactivated SARS-CoV-2 vaccines were analyzed for S-IgG, N-IgG, and Nabs. The results showed that the titer and seroconversion rate of S-IgG were significantly higher than those of N-IgG. The correlation between S-IgG and Nabs was higher compared to that of N-IgG. Based on this analysis, we further investigated the titer thresholds of S-IgG and N-IgG in predicting the seroconversion of Nabs. According to the threshold, we can quickly determine the positive and negative effects of the SARS-CoV-2 variant neutralizing antibody in individuals. These findings suggest that the S-IgG antibody is a better supplement to and confirmation of SARS-CoV-2 vaccine immunization. Full article

This systematic review investigates the intersection of early-onset colorectal cancer (EOCRC), sexual functioning, and associated quality of life (QoL), aiming to understand the comprehensive impact of EOCRC on these critical dimensions. Through an extensive search across PubMed, Scopus, and Embase up until November 2023, this study synthesized evidence from the literature while adhering to PRISMA guidelines. The studies included EOCRC patients under 50 years, which examined sexual functioning and QoL using validated instruments, and were published in English. After a rigorous screening process, five relevant studies were identified from an initial pool of 2184 articles. This review includes data from five studies involving 2031 EOCRC patients. The key findings revealed a high prevalence of sexual dysfunction, with up to 50% of men experiencing impotence and 58% reporting sexual dysfunction, alongside 36% of women in some studies. Pain was described by 12% to 31% of patients. Anxiety and depression were notably prevalent, affecting up to 69% of participants. EOCRC profoundly impacts sexual functioning and QoL, with a significant prevalence of sexual dysfunction and psychological distress among affected individuals. These findings suggest the need for oncological management strategies that include not only medical treatment but also psychological support and sexual health interventions. This systematic review emphasizes the importance of holistic patient care approaches, advocating for further research and clinical attention to address the complex needs of younger EOCRC patients. Full article

There have been previous studies conducted to predict postoperative lung function with pulmonary function tests (PFTs). Computing tomography (CT) can quantitatively measure small airway walls’ thickness, lung volume, pulmonary vessel volume, and emphysema area, which reflect the severity of respiratory diseases. These measurements are considered imaging biomarkers. This study aimed to predict postoperative lung function with imaging biomarkers. A retrospective analysis of 79 patients with lung cancer who had undergone lung surgery was completed. Postoperative lung function measured by forced expiratory volume in one second (FEV₁) was defined as an outcome. Preoperative clinico-pathological parameters and imaging biomarkers representing airway walls’ thickness, severity of emphysema, total lung volume, and pulmonary vessel volume were measured quantitatively in chest CT by an automated segmentation software, AVIEW COPD. Pi1 was defined as the first percentile along the histogram of lung attenuation that represents the degree of emphysema. Wafw was defined as the airway thickness, which was calculated by the full-width at half-maximum method. Logistic and linear regressions were used to assess these variables. If the actual postoperative FEV₁ was higher than the postoperative FEV₁ projected by a formula, the group was considered to be preserved. Among the 79 patients, 16 of the patients were grouped as a non-preserved group, and 63 of them were grouped as a preserved group. The patients in the preserved FEV₁ group had a higher vessel volume than the non-preserved group. Pi1 and Wafw were independent predictors of postoperative lung function. Imaging biomarkers can be considered significant variables in predicting postoperative lung function in patients with lung cancer. Full article

This systematic review evaluates the effectiveness of the Kansas City Cardiomyopathy Questionnaire (KCCQ) in assessing quality of life improvements among patients with heart failure (HF) undergoing various forms of exercise training rehabilitation, including telemedicine and in-person modalities, across all stages of HF, irrespective of ejection fraction (EF) and clinical status. The aim was to collate evidence from studies employing the KCCQ as a measure of quality of life (QoL). A comprehensive search strategy was implemented across PubMed, Scopus, and Embase databases, adhering to the PRISMA guidelines, including literature up until October 2023. Inclusion criteria encompassed studies on patients diagnosed with HF undergoing exercise training rehabilitation assessed by KCCQ. Nine articles met the inclusion criteria, involving a total of 3905 patients from various global locations and conducted between 2012 and 2022. Results indicated significant heterogeneity in exercise interventions and patient characteristics. Notably, high-intensity interval training (HIIT) showed a marked improvement in KCCQ scores (from 68.0 to 80.0) compared to moderate continuous training (MCT) and control groups, underscoring its potential for enhancing QoL. Additionally, a significant improvement in the 6-min walking test (6MWT) outcomes was observed, with an average increase of 106 m (95% CI: 60, 152) in one study, reflecting physical capacity enhancements. However, the difference in KCCQ scores between intervention and control groups was not statistically significant in several studies. In conclusion, the KCCQ’s effectiveness is highlighted by its ability to detect clinically meaningful improvements in QoL across diverse exercise modalities, including HIIT and MCT, tailored to the specific needs of HF populations. The consistent correlation between KCCQ score improvements and enhanced physical outcomes, such as the 6MWT, supports its reliability in capturing the nuanced benefits of exercise interventions on patient well-being. Full article