Reviews on Recent Clinical Trials - Volume 17, Issue 1, 2022

Introduction: The present article reports an overview of the studies about combination treatment with citicoline of Alzheimer’s (AD) and mixed dementia (MD). Methods: A Medline search was carried out by using the keywords Alzheimer’s dementia, mixed dementia, older people, treatment with citicoline, memantine, and acetylcholinesterase inhibitors (AchEIs). Results: Six studies were found to match the combination treatment of citicoline with AcheIs and/or memantine. The CITIRIVAD and CITICHOLINAGE studies were the first to report the potential benefits of adding citicoline to acetylcholinesterase inhibitors (AchEIs). Then, we added citicoline to memantine in the CITIMEM study, and finally, we demonstrated benefits in terms of delay in cognitive worsening with the triple therapy (citicoline + AchEIs + memantine). Other authors also reinforced our hypothesis through two further studies. Conclusion: Open, prospective studies are advised to confirm the utility of combination therapy with citicoline for the treatment of AD and MD.

Minimal residual disease (MRD) detection represents a great advancement in multiple myeloma. New drugs are now available that increase depth of response. The International Myeloma Working Group recommends using next-generation flow cytometry (NGF) or next-generation sequencing (NGS) to search for MRD in clinical trials. Best sensitivity thresholds have to be confirmed, as well as timing to detect it. MRD has proven as the best prognosticator in many trials and promises to enter also in clinical practice to guide future therapy.

Background: Covid-19 vaccination has started in the majority of the countries at the global level. Cancer patients are at high risk for infection, serious illness, and death from COVID-19 and need vaccination guidance and support. Guidance availability in the English language only is a major limit for recommendations’ delivery and their application in the world’s population and generates information inequalities across the different populations. Methods: Most of the available COVID-19 vaccination guidance for cancer patients was screened and scrutinized by the European Cancer Patients Coalition (ECPC) and an international oncology panel of 52 physicians from 33 countries. Results: A summary guidance was developed and provided in 28 languages in order to reach more than 70 percent of the global population. Conclusion: Language barrier and e-guidance availability in the native language are the most important barriers when communicating with patients. E-guidance availability in various native languages should be considered a major priority by international medical and health organizations that are communicating with patients at the global level.

Background and objectives: The goal of this study was to determine whether changes in life-space mobility and quality of life (QoL) recovered in patients with cardiovascular disease (CVD) during the first two waves of the pandemic of Coronavirus disease 2019 (COVID-19) in Japan. Methods: We performed a follow-up survey in 20 CVD patients using the Life-Space Assessment (LSA) scale and the five-level EuroQoL five-dimensional questionnaire (EQ-5D-5L), Japanese version, at three time points: January-March 2020 (before the first wave of the COVID-19 pandemic), July 2020 (following the first wave of the pandemic), and November 2020 (following the second wave of the pandemic). Results: The LSA score in November 2020 (median [interquartile range], 90 [83.5-100] points) did not recover from the July 2020 score (83 [76.5-93] points). However, the EQ-5D-5L QoL score in November 2020 (0.89 [0.82-1]) had improved from that in July 2020 (0.80 [0.71-0.87]). Conclusion: The QoL of CVD patients might have been more affected by psychological factors rather than physical factors during the first two waves of the COVID-19 pandemic in Japan.

Background: During general anesthesia, mechanical ventilation can cause pulmonary damage through mechanism of ventilator-induced lung injury, which is a major cause of post-operative pulmonary complications, which varies between 5 and 33% and increases the 30-day mortality of the surgical patient significantly. Objective: The aim of this review is to analyze different variables which played a key role in the safe application of mechanical ventilation in the operating room and emergency setting. Methods: Also, we wanted to analyze different types of the population that underwent intraoperative mechanical ventilation like obese patients, pediatric and adult population and different strategies such as one lung ventilation and ventilation in trendelemburg position. The peer-reviewed articles analyzed were selected according to PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) from Pubmed/Medline, Ovid/Wiley and Cochrane Library, combining key terms such as: “pulmonary post-operative complications”, “protective ventilation”, “alveolar recruitment maneuvers”, “respiratory compliance”, “intraoperative paediatric ventilation”, “best peep”, “types of ventilation”. Among the 230 papers identified, 150 articles were selected, after title - abstract examination and removing the duplicates, resulting in 94 articles related to mechanical ventilation in operating room and emergency setting that were analyzed. Results: Careful preoperative patient’s evaluation and protective ventilation (i.e., use of low tidal volumes, adequate PEEP and alveolar recruitment maneuvers) has been shown to be effective not only in limiting alveolar de-recruitment, alveolar overdistension and lung damage, but also in reducing the onset of Pulmonary Post-operative Complications (PPCs). Conclusion: Mechanical ventilation is like “Janus Bi-front” because it is essential for surgical procedures, for the care of critical care patients and in life-threatening conditions, but it can be harmful to the patient if continued for a long time and where an excessive dose of oxygen is administered into the lungs. Low tidal volume is associated with a minor rate of PPCs and other complications and every complication can increase the length of Stay, adding cost to NHS between 1580 and 1650 per day in Europe and currently the prevention of PPCS is the only weapon that we possess.

Background: In men with low levels of testosterone in the blood, it is believed that the symptoms can be regarded as an association between testosterone deficiency syndrome and related comorbidities. Aim: To investigate the effectiveness of testosterone therapy in patients with type 2 diabetes (T2D) and androgen deficiency. Materials and Methods: Testosterone replacement therapy was carried out in 26 men with T2D and clinically or laboratory-confirmed androgen deficiency. The age of the subjects ranged from 35 to 69 years old. Laboratory studies included determinations of the concentration of the hormones estradiol, luteinizing hormone (LH), and prostate-specific antigen (PSA). The observation period was 9 months. Results: The average level of total blood testosterone in the subjects before treatment was 9.4 mol/l and was likely lower than that of the control group (19.3 ± 1.6 nmol/l). The levels of total testosterone in the subjects ranged from 3.9 nmol/l to 10.7 nmol/l, and hormone levels measuring less than 8.0 nmol/l were observed in only 11 patients. After a course of testosterone replacement therapy, a stabilization in total testosterone levels at the level of reference values (as compared to the start of treatment) was observed in the blood of men with T2D after 9 months of observation and the administration of the fourth injection (16.83 ± 0.75 nmol/l). Conclusion: The use of long-acting injectable testosterone undecanoate leads to normalization of total testosterone levels in the blood of men with T2D and androgen deficiency, and LH levels in these patients are unlikely to change.

Background: Alterations in erythrocyte morphology parameters have been identified and associated with hematological disorders and other chronic and cardiovascular diseases. Erythrocytes are abundant in thrombus content. Their hemoglobin density and differences in the ratio of macrocytic and microcytic cells may be associated with hypercoagulopathy in those with a history of thrombosis. Objective: This cross-sectional study aimed to investigate the relationship between hemogram parameters and thrombophilia genetic parameters. Methods: A total of 55 patients whose thrombophilia panel was reviewed due to the diagnosis of thrombosis were included in the study. % MIC, % MAC, % HPO, % HPR and all hemogram parameters were measured using Abbott Alinity HQ. Prothrombin G20210A, MTHFR C677T, MTHFR A1298C, Factor V Leiden G169A and PAI-1 4G/5G mutations were studied using Real Time- PCR. Results: The MTHFR C677T mutation was detected in 58.2% of the patients. The Factor V Leiden mutation was detected in 5.5% of the patients. The MTHFR A1298C mutation was detected in 58.2%, The PAI mutation was detected in 74.5%, and the Factor 13 mutation was detected in 29% of the patients. Prothrombin G20210A mutation was not detected in any of the patients. Red blood cell (RBC) and hematocrit (Hct) values were higher in Factor 13 mutant group; the Hgb and Htc values were higher in the MTHFR C677T mutant group. The plateletcrit (PCT) and platelet (PLT) values were lower in MTHFR C677T mutant group. Conclusion: The MTHFR C677T and Factor 13 mutations may be associated with high Hct and Hgb, RBC, Hgb, and Htc values, respectively and coagulation tendency in patients with a history of thrombosis.

Background: Deep Neck Infections (DNIs) spread along fascial planes and involve neck spaces. Recently, their incidence has decreased due to the introduction of antibiotics; nevertheless, complications related to DNIs are often life-threatening. Objective: The purpose of this article is focused on the identification of predisposing factors of these complications, as well as on the development of a reliable therapeutic algorithm. Methods: Sixty patients with DNIs were enrolled from 2006 to 2019 for a retrospective study. The exclusion criteria for the present study were cellulitis, small abscesses responding to empiric or specific antibiotic therapy, or involvement of only one deep neck space. During the analysis, the following parameters of interest have been evaluated: gender, age, site of origin, pathways of spread, comorbidities, clinical features, bacteriology data, type of surgical approach required, complications, duration of hospitalization and mortality rate. On admission, microbial swab analysis was performed. Results: Diabetes Mellitus (DM), Chronic Obstructive Pulmonary Disease (COPD), iron deficiency anemia and the involvement of multiple spaces have been associated with a significantly higher risk of developing complications. Most of our patients had polymicrobial infections. All patients underwent surgical drainage. The complication rate had occurred in 56.6% of patients, while death in 18.3%. Conclusion: DNIs represent a medical and surgical emergency with potentially serious complications; thus, avoidance of diagnostic delay is mandatory. Our preliminary data suggest the importance of evaluating the extent of infections because the involvement of multiple spaces requires timely surgery due to the higher risk of complications and mortality.

Background: It has been shown that autonomic dysfunction in fibromyalgia can be assessed by the Composite Autonomic Symptom Score (COMPASS) questionnaire. More recently, a refined and much abbreviated 31-item version of the questionnaire has been developed, the COMPASS 31. Objectives: First, to determine whether the COMPASS 31 can assess changes in autonomic function in fibromyalgia. Second, to assess whether the COMPASS 31 values in fibromyalgia patients are positively correlated with scores on the Revised Fibromyalgia Impact Questionnaire (FIQR). Methods: A cross-sectional, case-controlled study was carried out with 25 fibromyalgia patients and 26 healthy controls. Results: The two groups were matched for age, sex and ethnicity, but not for body mass index (BMI). The total mean (standard error) COMPASS 31 for the fibromyalgia patients, 37.2 (1.8), differentiated the patients from the controls (9.5 (1.4); p < 0.00000001). The scores were greater in the fibromyalgia patients across all COMPASS 31 autonomic domains, namely orthostatic intolerance (p < 0.00000001), and vasomotor (p < 0.0001), secretomotor (p < 0.000001), gastrointestinal (p < 0.000001), bladder (p < 0.00001) and pupillomotor functions (p < 0.00000001). The total COMPASS 31 values were positively correlated with FIQR scores (rs = 0.45, p < 0.05). General linear modelling of the COMPASS 31 scores showed that only group status (fibromyalgia or control) was significant (p = 3.4 × 10^-16), with age, sex and BMI being non-significant. Conclusion: This study confirms that non-pain autonomic dysfunction symptoms occur in fibromyalgia and can be assessed with the COMPASS 31.

Background: Pediculosis is an infestation of lice affecting mostly children and spreads by direct contact with the hair of someone infected. Although topical application of a pediculicide such as permethrin shampoo is the most common cure for head lice, the addition of alternative treatments is necessary due to permethrin resistance and some safety concerns, including irritation, burning sensation, tingling, and breathing problems. Recent studies have indicated that ozone, which is an allotropic form of oxygen, may have anti-pediculosis effects. Objective: This study focused on the evaluation of an ozonated olive oil topical lotion for the treatment of pediculosis and the comparison of its effects with permethrin shampoo. Methods: 121 patients with proven head pediculosis were divided into two groups. They were treated with either topical ozonated olive oil lotion or permethrin shampoo for one week. Results: It was shown that the ozonation process enormously improved the physico-chemical properties of olive oil. Specifically, acid and peroxide values increased 60 fold and 200 fold, respectively, while there was a sharp decline for the iodine index (81.8±1.28 to 0 g iodine per 100 g). Additionally, all patients who received the ozonated olive oil lotion were entirely cured after one week of treatment, while those who were treated with permethrin, required to receive more. Statistical analysis of the data also proved this claim. Conclusion: The prepared lotion has shown significant effects in controlling head lice. Thus, it can be prescribed as an effective anti-pediculosis medicine which is biocompatible and has high potential.