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Emina Smajić, D. Avdić, Aleksandra Pašić, Alden Prcić, Maja Stancic

Background: Scientific research is usually classified as quantitative or qualitative. However, methodologists are increasingly emphasizing the integration of qualitative and quantitative data as the center of mixed methods (mix methodologies). Mixed research method implies the use of different research methods, ie. quantitative and qualitative methods in one study. Objective: The aim of this review paper is to present the purpose of using a mixed methodology in health research. Methods: The relevant articles were searched from online data sources including PubMed and Google Scholar. Results: This approach to the use of mixed methods creates opportunities for a deeper study of various problems. The purpose of using mixed research methods is to obtain valid answers to research questions, however the researcher may still have different reasons or purposes for which he wants to strengthen the research study and its conclusions by applying mixed methods. The use of mixed scientific methodology is widely used in the field of health outcomes and should not be limited to a closed list of possible methodological options. Conclusion: Recently, there has been an increase in the number of scientific studies in healthcare that use mixed research methods. The advantage of applying this scientific method is that through the triangulation of data obtained by different (quantitative / qualitative) approaches, we get a deeper and more complete picture of the phenomenon in health care that we observe.

C. Caldas, M. Rescigno, S. Turajlic, A. Madabhushi, Zemin Zhang, P. Lito, Christine E. Brown, K. Pantel et al.

In the past 20 years we have seen the rise of a new era of cancer research that moved its focus away from the cancer cell itself and revealed a complexity of interactions, both within the tumor and with the host, that ultimately dictate the evolution and progression of the disease. We have witnessed the development of immunotherapies that changed the fate of many patients and new diagnostic strategies with the potential of changing clinical practice. In this article, several experts discuss what lies ahead.

Faris Kadić, E. Begić, Mirza Pašić, Ali Gavrankapetanović, A. Mujaković, Aida Pidro, Ada Djozic

Background: Angiotensin-converting enzyme 2 (ACE2) is not only an enzyme but also a functional receptor on cell surfaces through which Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). The exact mechanism by which arterial hypertension (particularly regulated) could affect the presentation and outcome of Coronavirus disease-19 (COVID-19) has not been fully elucidated. Objective: The aim of this study was to analyze the parameters of patients with verified COVID-19 and existing arterial hypertension at the time of hospital admission and to develop neural network model. Methods: The research had a cross-sectional descriptive and analytical character, and included patients (n=634) who were hospitalized in the General Hospital “Prim. dr. Abdulah Nakas” in Sarajevo, Bosnia and Herzegovina, in the period from 01 Sep 2020 to 01 May 2021. From the hospital information system, which is used in everyday clinical work, laboratory parameters at admission were verified, along with demographic data, the comorbidities, while the outcome (recovery, death) was recorded thirty days after the admission. Results: Out of the total number, in 314 patients (200 males), arterial hypertension was verified, out of which, 56 (17.83%) patients died. Patients were divided into two groups, according to outcome, i.e., whether they survived COVID-19 infection or not. A significant difference in age (p = 0.00), erythrocyte count (p = 0.03), haemoglobin (p = 0.05), hematocrit (p = 0.03), platelets count (p = 0.00), leukocytes (p = 0.01), neutrophils (p = 0.00), lymphocytes (p = 0.00), monocytes (p = 0.00), basophils (p = 0.00), eosinophils (p = 0.00), C-reactive protein (p = 0.00) and D-dimer (p = 0.01) was noted. When patients who died and had hypertension were compared with those who died and did not have hypertension (n = 15), out of alll the analyzed parameters, the only significant difference was established in the patient’s age (p = 0.00). In case when patients with hypertension who died were compared to patients with hypertension and diabetes mellitus who died no significant differences were found between features. Conclusion: Patients with hypertension and COVID-19 who died were older, had higher values of erythrocytes, hemoglobin, hematocrit, leukocytes, neutrophils, CRP and D-dimer, and lower values of platelets, lymphocytes, monocytes, basophils and eosinophils count at admission. Compared to deaths without hypertension, the only difference that was established was that patients with hypertension were older.

J. Heugenhauser, Malik Galijašević, S. Mangesius, G. Goebel, J. Buchroithner, F. Erhart, J. Pichler, G. Widhalm et al.

Simple Summary In order to compare responses to different therapies among clinical trials and to differentiate between therapy-induced changes and true tumor progression, reliable response parameters are crucial. With the advent of targeted and immunologic treatments, several assessment tools have been proposed. In this post hoc analysis we compared assessment criteria according to MacDonald, RANO, mRANO, iRANO as well as Vol-RANO and Vol-mRANO in patients with newly diagnosed glioblastoma treated with standard of care (SOC) ± tumor lysate-charged autologous dendritic cells (Audencel). We found that the best correlation between progression-free survival (PFS) and overall survival (OS) was seen for mRANO and Vol-mRANO. Interestingly, iRANO was not superior for predicting OS in patients treated with Audencel. Abstract Introduction: In this post hoc analysis we compared various response-assessment criteria in newly diagnosed glioblastoma (GB) patients treated with tumor lysate-charged autologous dendritic cells (Audencel) and determined the differences in prediction of progression-free survival (PFS) and overall survival (OS). Methods: 76 patients enrolled in a multicenter phase II trial receiving standard of care (SOC, n = 40) or SOC + Audencel vaccine (n = 36) were included. MRI scans were evaluated using MacDonald, RANO, Vol-RANO, mRANO, Vol-mRANO and iRANO criteria. Tumor volumes (T1 contrast-enhancing as well as T2/FLAIR volumes) were calculated by semiautomatic segmentation. The Kruskal-Wallis-test was used to detect differences in PFS among the assessment criteria; for correlation analysis the Spearman test was used. Results: There was a significant difference in median PFS between mRANO (8.6 months) and Vol-mRANO (8.6 months) compared to MacDonald (4.0 months), RANO (4.2 months) and Vol-RANO (5.4 months). For the vaccination arm, median PFS by iRANO was 6.2 months. There was no difference in PFS between SOC and SOC + Audencel. The best correlation between PFS/OS was detected for mRANO (r = 0.65) and Vol-mRANO (r = 0.69, each p < 0.001). A total of 16/76 patients developed a pure T2/FLAIR progressing disease, and 4/36 patients treated with Audencel developed pseudoprogression. Conclusion: When comparing different response-assessment criteria in GB patients treated with dendritic cell-based immunotherapy, the best correlation between PFS and OS was observed for mRANO and Vol-mRANO. Interestingly, iRANO was not superior for predicting OS in patients treated with Audencel.

Amanda S. Mahoney, Yassin Khalifa, E. Lucatorto, E. Sejdić, James L. Coyle

Clinicians and researchers commonly judge the completeness of hyoid displacement from videofluoroscopic swallow study (VFSS) videos. Judgments made during the clinical exam are often subjective, and post-examination analysis reduces the measure’s immediate value. This study aimed to determine the validity and feasibility of a visual, anatomically scaled benchmark for judging complete hyoid displacement during a VFSS. The third and fourth cervical vertebral bodies (C3 and C4) lie at roughly the same vertical position as the hyoid body and are strongly correlated with patient height. We hypothesized that anterior and superior displacement of the hyoid bone would approximate the height of one C3 or C4 body during safe swallows. Trained raters marked points of interest on C3, C4, and the hyoid body on 1414 swallows of adult patients with suspected dysphagia (n = 195) and 50 swallows of age-matched healthy participants (n = 17), and rated Penetration Aspiration Scale scores. Results indicated that the mean displacements of the hyoid bone were greater than one C3 unit in the superior direction for all swallows from patient and healthy participants, though significantly and clinically greater in healthy participant swallows (p < .001, d > .8). The mean anterior and superior displacements from patient and healthy participant swallows were greater than one C4 unit. Results show preliminary evidence that use of the C3 and/or C4 anatomic scalars can add interpretive value to the immediate judgment of hyoid displacement during the conduct of a clinical VFSS examination.

Z. Bouzid, S. Al-Zaiti, R. Bond, E. Sejdić

The electrocardiogram (ECG) records the electrical activity in the heart in real-time, providing an important opportunity to detecting various cardiac pathologies. The 12-lead ECG currently serves as the “standard” ECG acquisition technique for diagnostic purposes for many cardiac pathologies other than arrhythmias. However, the technical aspects of acquiring a 12-lead ECG are not easy and its usage is currently restricted to trained medical personnel, limiting the scope of its usefulness. Remote and wearable ECG devices have attempted to bridge this gap by enabling patients to take their own ECG using a simplified method at the expense of a reduced number of leads, usually a single-lead ECG. In this review article, we summarize the studies which investigate the use of remote ECG devices and their clinical utility in diagnosing cardiac pathologies. Eligible studies discussed FDA-cleared, commercially available devices that were validated on an adult population. We summarize technical logistics of signal quality and device reliability, dimensional and functional features, and diagnostic value. In summary, our synthesis shows that reduced-set ECG wearables have huge potential for long-term monitoring, particularly if paired with real-time notification techniques. Such capabilities make them primarily useful for abnormal rhythm detection and there is sufficient evidence that a remote ECG device can be more superior to traditional 12-lead ECG in diagnosing specific arrhythmias such as atrial fibrillation. However, this review identifies important challenges faced by this technology, highlighting the limited availability of clinical research examining their usefulness.

Nusret Salkica, A. Begić, S. Zubović, Šejla Cerić, Amila Bašić, A. Šehić, F. Julardžija, Enis Tinjak

Background: The use of resolution recovery (RR) in bone and myocardial perfusion imaging is becoming increasingly popular in nuclear medicine departments. RR produces reconstructed images that show improved spatial resolution and signal-to-noise ratio compared with conventional single-photon emission computed tomography (SPECT) images. Objective: To evaluate the impact of the ordered subset expectation maximization (OSEM) RR modality on preserving noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) for short SPECT acquisition. Methods: This prospective study was conducted on 80 patients. Full SPECT acquisition was performed as a standardized protocol, while reduced acquisition was achieved with the Poisson resampling method. Noise, SNR, and CNR were measured for different reconstruction parameters for the same image levels. The impact of surface area and body mass index was also measured for the same reconstruction parameters. Results: The results show significantly higher SNR and CNR for the Evolution for Bone protocol compared to the other two reconstruction protocols for full and reduced SPECT acquisition. With the shortening of the SPECT acquisition, an increase in the value of noise was recorded. SNR and CNR decreased with the reduction in SPECT acquisition. Conclusion: The Evolution for Bone protocol for all three analyzed acquisition protocols had the lowest noise values. The highest SNR and CNR were recorded in the Evolution for Bone protocol for the three acquisition protocols and SPECT acquisition time can be reduced from 20 to 10 min for bone SPECT.

Background: Acute left ventricular free wall rupture (LVFWR) is a life-threatening complication of myocardial infarction that requires urgent intervention. Surgical repair has continued to be the treatment of choice. Studies suggest a posterolateral or inferior infarction is more likely to result in free wall rupture than an anterior infarction. LVFWR generally results in death within minutes of the onset of recurrent chest pain, and on average was associated with a median survival time of 8 hours. Prompt diagnosis and management can lead to successful treatment for LVFWR. Objective: The aim of this article was to present an emergency case with an LVFWR in a COVID-19 patient who suffers from AMI and was treated with PCI stents in the ramus intermedius and circumflex coronary artery. Case report: We present an emergency case with an LVFWR in a COVID-19 patient who suffers from AMI and was treated with PCI stents in the ramus intermedius and circumflex coronary artery. Although dual antiplatelet therapy introduction and good outcome of PCI were achieved, soon after instant thrombosis of both stents appear to result in transmural necrosis and LVFWR. Urgent catheterization was performed and diagnosed in-stent thrombosis where the ventriculography confirmed LVFWR of the posteroinferior wall. Urgent surgery was performed. Transmural necrosis was noticed alongside the incision line. The incision is sawn with 4 U-stitches (Prolen 2.0 with Teflon buttressed stitches). Another layer of fixation was made by Prolen 2.0 running stitches reinforced with Teflon felts from both sides. A large PTFE patch was fixed to epicardium over the suture line by Prolen 6.0 running stitch and BioGlue was injected in-between patch and LV (Figures 8 and 9). After aortic cross-clamp removal, the sinus rhythm was restored. Conclusion: Despite the high mortality, the urgency and the complexity of surgical treatment the early diagnosis plays a key role in the management of postinfarction LVFWR patients presenting a case of preserved postoperative left ventricular function and accomplished good functional status, as presented in our case.

Riad Hajdarevic, A. Lande, J. Mehlsen, Anne Rydland, Daisy D. Sosa, E. Strand, O. Mella, F. Pociot et al.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disease of unknown etiology and pathogenesis, which manifests in a variety of symptoms like post-exertional malaise, brain fog, fatigue and pain. Hereditability is suggested by an increased disease risk in relatives, however, genome-wide association studies in ME/CFS have been limited by small sample sizes and broad diagnostic criteria, therefore no established risk loci exist to date. In this study, we have analyzed three ME/CFS cohorts: a Norwegian discovery cohort (N=427), a Danish replication cohort (N=460) and a replication dataset from the UK biobank (N=2105). To the best of our knowledge, this is the first ME/CFS genome-wide association study of this magnitude incorporating 2532 patients for the genome-wide analyses and 460 patients for a targeted analysis. Even so, we did not find any ME/CFS risk loci displaying genome-wide significance. In the Norwegian discovery cohort, the TPPP gene region showed the most significant association (rs115523291, P=8.5x10-7), but we could not replicate the top SNP. However, several other SNPs in the TPPP gene identified in the Norwegian discovery cohort showed modest association signals in the self-reported UK biobank CFS cohort, which was also present in the combined analysis of the Norwegian and UK biobank cohorts, TPPP (rs139264145; P= 0.00004). Interestingly, TPPP is expressed in brain tissues, hence it will be interesting to see whether this association with time will be verified in even larger cohorts. Taken together our study, despite being the largest to date, could not establish any ME/CFS risk loci, but comprises data for future studies to accumulate the power needed to reach genome-wide significance.

Reynold C. Ly, Tyler Shugg, Ryan Ratcliff, Wilberforce Osei, V. Pratt, Bryan Schneider, Milan Radovich, Steven M Bray et al.

Azra Bureković, Z. Ašimi, A. Divanović, Dženan Halilović

Background: COVID-19 infection has shown many complications on all organ systems, including the pancreas, during the acute phase of infection and in the post covid period. Objective: Our goal was to compare the frequency of patients with type 1 and type 2 diabetes in the Outpatient Clinic “Srce Sarajeva”, in the year before COVID-19, 2019, and during the COVID-19 infection, in 2020 and 2021. Our second goal was to monitor the incidence of diabetes after COVID-19 infection, the time of onset after the acute phase of the disease, and treatment options for individual patients depending on the value of glucose. Methods: The study was designed as a retrospective-prospective, with the consent of the Director of the Outpatient Clinic “Srce Sarajeva”, and patient consent, in the period of January 2019 to December 2021. The study included 371 patients at the age between 18-70. Results: In 2020 and 2021 there was a significant difference in the number of patient diagnosed with diabetes who came for examination, compared to 2019. The number of new-onset diagnosed patients with type 1 and type 2 diabetes was significantly higher in 2020 and 2021 compared to 2019. In 2020, out of five newly discovered type 1, 3 of them, with an average age of 23 (+/- 1-4), overcame COVID-19 infection, and diabetes was detected 3-4 weeks after overcoming COVID-19 infection. Of the 122 type 2 patients, 19 were newly diagnosed, 47 were of average age (+/- 2-6), 13 were COVID-19 infected, and diabetes was detected 4-6 weeks after infection. In 2021, out of 4 newly discovered type 1, 3 of them, with an average age of 22 (+/- 1-2), overcame COVID-19 infection, and diabetes was detected 2-3 weeks after overcoming COVID-19 infection. Of the 114 type 2 patients, 32 were newly diagnosed, 45 were of average age (+/- 2-6), 23 were COVID-19 infected, and diabetes was detected 6-8 weeks after infection. Conclusion: COVID-19 infection adversely affects the pancreatic tissue leading to the clinical picture of type 1 and type 2 diabetes, and all patients, especially those at high risk of developing the disease suggest blood sugar testing, 3-4 weeks after the acute phase of the disease, and earlier if they were on corticosteroid therapy.

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