ISSN: 2148-4902 | E-ISSN: 2536-4553
Northern Clinics of İstanbul - North Clin Istanb: 11 (2)
Volume: 11  Issue: 2 - 2024
EDITORIAL
1. Front Matter

Pages I - VIII

RESEARCH ARTICLE
2. The effect of Myrtus communis L. extract on nephrolithiasis model in rats
Busra Ertas, Dogancan Dorucu, Oznur Gulerturk, Ali Sen, Ozge Cevik, Sule Cetinel, Pinar Eker, Asuman Akgun, Tarik Emre Sener, Goksel Sener
PMID: 38757104  PMCID: PMC11095334  doi: 10.14744/nci.2023.09068  Pages 91 - 98
OBJECTIVE: Nephrolithiasis is a common urological disease that can lead to renal failure. Oxidative stress has been shown to be a contributing factor for nephrolithiasis and many agents have been studied to prevent and treat oxidative stress-related nephrolithiasis and renal damage. Myrtus communis (MC) extract has been shown to be an important antioxidant in different animal models. In this study, MC extract was administered preventively or therapeutically to rats with kidney stones, and its effectiveness was investigated.
METHODS: Wistar albino rats were divided into four groups (n=8); control (C), ethylene glycol (EG), EG+preventive MC, and EG+curative MC groups. The nephrolithiasis model was created by adding 0.75% EG to drinking water for 8 weeks. Ultimately, 24-hour urine was collected to measure calcium, citrate, and creatinine levels. After decapitation, kidney tissues were harvested for histological analyses, measurement of osteopontin and 8-hydroxydeoxyguanosine (8-OHdG) levels, and N-acetyl-β-glucosaminidase (NAG), myeloperoxidase (MPO) and caspase-3 activities.
RESULTS: In 24-hour urine samples, calcium, citrate and creatinine levels were decreased in the EG group, while oxalate levels were increased and in treatment groups these parameters returned to control levels. MPO, 8-OHdG, caspase-3 and NAG activity were significantly increased in tissue and these changes were reversed in both MC groups. Histological findings also supported the biochemical parameters.
CONCLUSION: MC can reduce oxidative stress and histopathological changes in kidney tissues in rat nephrolithiasis model when used as either a preventive or therapeutic agent. If supported with further clinical trials, MC might have clinical implications in preventing oxidative renal cell injury and ultimately kidney stone formation.

3. Should we rely on frozen section during the reimplantation stage of revision knee arthroplasty?
Aydan Kilicarslan, Kaan Yuksel, Nuran Sungu
PMID: 38757108  PMCID: PMC11095333  doi: 10.14744/nci.2023.90699  Pages 99 - 104
OBJECTIVE: To compare Frozen Section (FS) results during the reimplantation stage of revision knee arthroplasty, in patients without clinical signs of infection but with preoperative inconclusive serum inflammatory markers.
METHODS: Sections were revisited the day after surgery. Intraoperative FS (iFS) was accepted as positive when the presence of >5 polymorphonuclear neutrophils (PMNLs) in 5 separate high-power fields was determined according to the consensus criteria of the International Consensus on Musculoskeletal Infection. The clinical outcomes, cultures and diagnostic values of iFS and review FS (rFS) were analyzed.
RESULTS: No complications developed after reimplantation in 66 (84.6%) of the 78 evaluated patients. Complications developed in 12 patients, six of whom were treated with re-explantation, four with arthrodesis and two with above-the-knee amputation. Both iFS and rFS yielded insignificant sensitivity and specificity (25% and 45.5%, 25% and 45%, respectively). There was no statistically significant difference between definitive culture and iFS and rFS.
CONCLUSION: iFS evaluation is insufficient to exclude recovery from periprosthetic joint infection (PJI). Diagnosis of recurrence of infection in patients with indefinite serum inflammatory markers between the explantation and reimplantation interval remains challenging due to massive fibrosis that makes proper tissue sampling difficult. The attending physician should closely monitor clinical findings.

4. Evaluation of post-acute-COVID-19, and long-COVID symptoms with a questionnaire: Within one year, a longitudinal study
Canan Emiroglu, Murat Dicle, Serap Demirelli Ozagar, Suleyman Gorpelioglu, Cenk Aypak
PMID: 38757107  PMCID: PMC11095331  doi: 10.14744/nci.2023.58908  Pages 105 - 114
OBJECTIVE: Long-term consequences of COVID-19 vary widely, representing a growing global health challenge. The aim of this report was to define the presence of symptoms in post-acute-COVID-19 syndrome (PCS) patients and to assess the frequency, associated factors, and the spectrum of persistent symptoms.
METHODS: In this longitudinal study, 487 adults with a previously diagnosed “Severe Acute Respiratory Syndrome Coronavirus 2” (SARS-CoV-2) who admitted to COVID-19 follow-up outpatient clinic between December 1, 2020 and November 31, 2021 were interviewed face-to-face three times. Data was collected on patient demographics, comorbidities, and symptoms. A questionnaire of 160 questions was asked and organized into the following: identification and consent, socio-demographic/ epidemiological characteristics, previous medical history, diagnosis and clinical presentation of acute COVID-19, as well as systematic symptoms. Data were evaluated using univariate comparisons and multiple logistic regression.
RESULTS: The most prevalent symptoms among all PCS patients during their initial visit were dyspnea, weakness, forgetfulness, fatigue, and arthralgia respectively. The most common symptoms in patients with 6 months or more time from discharge to follow-up at the first and second visits, appear to be persistent. While incidence rates decreased by the third visit, the five most common symptoms remained the same. The possibility of weakness and arthralgia was found to be higher in non-hospitalized patients. Females were associated with the most common persistent symptoms and the strongest association was with arthralgia.
CONCLUSION: A large number of COVID-19 survivors had continuing symptoms at the first year of post-COVID-19-infection. Neither the presence of comorbidities of the patient nor smoking status were associated with the severity of PCS symptoms. A better understanding of the mechanisms, predisposing factors and evaluation require a multidisciplinary team approach.

5. A potential biomarker of disease activity in systemic lupus erythematosus, systemic immune-inflammation index
Muhammed Recai Akdogan, Meltem Alkan Melikoglu
PMID: 38757099  PMCID: PMC11095327  doi: 10.14744/nci.2023.90132  Pages 115 - 119
OBJECTIVE: Biomarkers using routine laboratory tests accurately presenting systemic lupus erythematosus (SLE) disease activity may have important practical values in clinical settings. The primary purpose of this study was to investigate neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII; neutrophil X platelet/lymphocyte) as potential biomarkers of disease activity in cases with SLE.
METHODS: In this case-control observational study, cases with SLE and demographically similar healthy controls were included. For clinical evaluation demographic features, disease duration and drugs were recorded. SLE clinical disease activity was assessed with SLEDAI scores. For laboratory assessments; erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and C3-C4 levels and anti-dsDNA positivity were recorded. Based on the simultaneous complete blood count (CBC) of the participants NLR, PLR and SII were calculated. The correlation between clinical and laboratory data was analyzed.
RESULTS: 68 cases with SLE (64 women, 8 men) and 69 controls (65 women, 4 men) were included in this investigation. The demographic features of the cases and controls were similar. ESR, CRP, NLR, PLR and SII scores were statistically higher in cases with SLE than controls (p<0.000). Statistically significant positive correlations between SLEDAI and NLR, PLR and SII scores were demonstrated (p=0.01, r=0.505; 0.414; 0.698, respectively). We determined a cut-off value of SII as 681,3 presenting 77% sensitivity and 76% specificity to discriminate no-mild disease activity and moderate-higher SLE disease activity status. The SII cut-off value was determined as 681,3 presenting 77% sensitivity and 76% specificity (p<0.000, and AUC=0.930).
CONCLUSION: CBC indices were shown to be higher in cases with SLE than healthy controls in our study. By presenting a strong correlation with disease activity and discriminating ability of disease status, SII might serve as a biomarker supporting clinical evaluation in SLE.

6. Comparison of two different respiratory monitoring systems with 4D-CT images for target volume definition in patients undergoing para-aortic nodal irradiation
Sefika Arzu Ergen, Songul Karacam, Tuba Kurt Catal, Fazilet Oner Dincbas, Didem Colpan Oksuz, Ismet Sahinler
PMID: 38757101  PMCID: PMC11095336  doi: 10.14744/nci.2023.06856  Pages 120 - 126
OBJECTIVE: Today, respiratory movement can be monitored and recorded with different methods during a simulation on a four-dimensional (4D) computed tomography (CT) device to be used in radiotherapy planning. A synchronized respiratory monitoring system (RPM) with an externally equipped device is one of these methods. Another method is to create 4D images of the patient’s breathing phases without the need for extra equipment, with an anatomy-based software program integrated into the CT device. Our aim is to compare the RPM system and the software system (Deviceless) which are two different respiratory monitoring methods used in tracking moving targets during 4D-CT imaging and to assess their clinical usability.
METHODS: Ten patients who underwent paraaortic nodal irradiation were enrolled. The simulation was performed using intravenous contrast material on a 4D-CT device with both respiratory monitoring methods. The right/left kidneys and renal arteries were chosen as references to evaluate abdominal organ movement. It was then manually contoured one by one on both sets of images. The images were compared volumetrically and geometrically after rigid reconstruction. The similarity between the contours was determined by the Dice index. Wilcoxon test was used for statistical comparisons.
RESULTS: The motion of the kidneys in all three directions was found to be 0.0 cm in both methods. The shifts in the right/ left renal arteries were submillimetric. The Dice index showed a high similarity in both kidney and renal artery contours.
CONCLUSION: In our study, no difference was found between RPM and Deviceless systems used for tracking and detection of moving targets during simulation in 4D-CT. Both methods can be used safely for radiotherapy planning according to the available possibilities in the clinic.

7. Evaluation of patients diagnosed with brain death in the intensive care unit: 10 years of tertiary center experience in Istanbul
Kadir Arslan, Ayca Sultan Sahin
PMID: 38757109  PMCID: PMC11095337  doi: 10.14744/nci.2023.06937  Pages 127 - 132
OBJECTIVE: Early and accurate diagnosis of brain death in intensive care units (ICU) is essential for organ transplantation.
This study aimed to evaluate the cases diagnosed with brain death in the ICU of a tertiary center in Istanbul.
METHODS: The cases diagnosed as brain death in the ICU during the ten years between January 2013 and September 2022 were evaluated retrospectively. The demographic characteristics of the patients, the diagnosis of hospitalization in the ICU, the time from arrival to the ICU until the diagnosis of brain death, the somatic survival time after the diagnosis of brain death, the acceptance rate of organ donation by the families and the organs removed were evaluated.
RESULTS: A total of 44 patients were diagnosed with brain death. The mean age of the cases was 39.7±17.4 years, and 63% were male. The most common hospitalization diagnosis was intracranial hemorrhage (81.8%). Traffic accidents, hypertensive and aneurysm-related hemorrhages, gunshot wounds, and falls from height were the most common causes of intracranial hemorrhage. Patients were admitted to the ICU most frequently from the emergency department (54%). The mean time to brain death was 7.9±6.2 days, and the somatic survival time was 1.9±1.9 days in patients who did not receive organ transplantation. While the apnea test was positive in 91% of the cases, the apnea test could not be completed in 9% of the cases. While relatives of 7% (n=3) of the cases accepted organ donation, a patient was not allowed to be an organ donor for medical reasons. Organ transplantation was performed in two patients (5%).
CONCLUSION: As in the whole world, getting treatment as soon as possible for the patients waiting on the organ transplant list in Turkiye by increasing the number of organs to be obtained from cadavers. In cases with suspected brain death in the ICU, diagnosing brain death as soon as possible and conducting family interviews with trained organ transplant coordinators will increase the number of cadaver donors. However, we think policies should be developed to ensure that society is informed and encouraged about brain death and organ donation.

8. Factors associated with acute kidney injury in patients undergoing transcatheter aortic valve implantation: Short-term outcomes and impact of right heart failure
Dilek Aslan Kutsal, Sait Terzi
PMID: 38757106  PMCID: PMC11095335  doi: 10.14744/nci.2024.87864  Pages 133 - 139
OBJECTIVE: Transcatheter aortic valve implantation (TAVI) was developed as an alternative to surgery for symptomatic, high-risk patients with severe aortic stenosis (AS). Acute kidney injury, a major complication of TAVI, is associated with a poor prognosis. In our study, we planned to investigate the effect of right heart failure on the development of acute kidney injury after TAVI and other factors contributing to the development of AKI.
METHODS: Between January 2015 and December 2020, 198 patients who underwent TAVI due to severe symptomatic aortic stenosis at Dr. Siyami Ersek Cardiovascular Surgery Hospital were screened. Local ethics committee approval was obtained (HNEAH-KAEK 2021/134-3343). Transthoracic echocardiographic findings and laboratory evaluations were recorded. Patients were evaluated according to Acute Kidney Injury Network (AKIN) criteria.
RESULTS: The rate of AKI after TAVI was found to be 41.9%. The mean age of patients who developed AKI was higher (80.90±6.8). AKI development rates were higher in the female gender (68.7%) and patients with hypertension (44.8%). It was observed that the risk of developing AKI was higher in patients who underwent TAVI and developed AKI afterwards, es- pecially in patients with stage-3 and stage-4 advanced CKD before TAVI (p<0.01) We did not find an independent relationship between AKI and right-heart failure in our analysis.
CONCLUSION: We observed that chronic kidney disease before TAVI, advanced age, and female gender are important determinants of the development of AKI after TAVI. Although a relationship between TAVI and right heart failure has not been demonstrated, large-scale studies are needed in the future.

9. Impact of central sensitization on clinical parameters in patients with rheumatoid arthritis
Nilgun Mesci, Erkan Mesci, Emine Unkun Kandemir, Duygu Geler Kulcu, Talha Celik
PMID: 38757102  PMCID: PMC11095328  doi: 10.14744/nci.2023.81231  Pages 140 - 146
OBJECTIVE: This study aimed to investigate the effects of central sensitization (CS) on pain sensitivity, disease activity,
neuropathic symptoms and quality of life (QoL) in patients with rheumatoid arthritis (RA).
METHODS: Sixty patients diagnosed with RA according to the American College of Rheumatology and the European League Against Rheumatism (ACR/EULAR) 2010 classification criteria were included in the study. Patient assessment tools included visual analog scale (VAS) for pain, algometer for pain pressure threshold (PPT), disease activity score in 28 joints (DAS-28) for disease activity (DA), central sensitization inventory (CSI) for CS and rheumatoid arthritis QoL questionnaire for QoL.
RESULTS: Central sensitization was identified in 29 (48.3%) patients. Although erythrocyte sedimentation rate (ESR), C-reactive protein and swollen joint count were comparable between patients with or without CS, higher VAS, tender joint count and DAS-28 scores were observed in patients with CS (all p<0.05). Pain pressure thresholds (PPT) at the wrist (PPTW) and the trapezius muscle (PPTT) were lower in patients with CS (p=0.004, p=0.001, respectively). It was found that neuropathic pain components increased and quality of life decreased as CSI scores increased (all p=0.000).
CONCLUSION: The presence of CS leads to pain sensitivity as well as overestimation of disease activity in RA patients. The presence of CS should not be overlooked in RA patients to avoid overtreatment for inflammation and to determine the treatment need for nociplastic pain.

10. Rheumatoid factor titers, but not Fc fragments, may be strongly associated with drug survival of anti-TNF agents in patients with rheumatoid arthritis
Huseyin Kaplan, Gizem Cengiz, Isa Cuce, Senem Sas, Emre Senkoy, Mustafa Calis, Orhun Ozturk, Huseyin Demir, Mehmet Kirnap
PMID: 38757098  PMCID: PMC11095329  doi: 10.14744/nci.2023.01643  Pages 147 - 157
OBJECTIVE: To investigate the effects of both the Fc fragment in tumor necrosis factor (TNF) inhibitors and rheumatoid
factor (RF) titers on treatment survival, disease activity, and laboratory parameters in patients with rheumatoid arthritis (RA).
METHODS: In this retrospective cohort study, patients with RA who had started any anti-TNF therapy between January 2017 and March 2020 and who had stayed on this treatment for at least six months were included. The data of the patients were compared separately according to continuation or discontinuation of treatment and the presence or absence of Fc portion in the structure of anti-TNFs. Patients who were taking certolizumab pegol (CZP) without the Fc fragment were placed in the “without Fc group” (wo/Fc), while patients who were taking other drugs (adalimumab, etanercept, golimumab, and infliximab) were placed in the “with Fc group” (w/Fc).
RESULTS: Among the 221 RA patients whose data were available, 52 patients met the inclusion criteria and were included in the study. There was a significant difference in the DAS28-CRP score between wo/Fc group and w/Fc group in the third month of treatment (p=0.012). However, this difference did not persist at the sixth month of treatment (p=0.384). According to the cox-regression results, RF titers were determined to have a significant impact on the drug survival of anti-TNF agents when adjustments were made for the effects of other candidate predictors (Hazard ratio: 1.007 (1.002–1.012), p=0.009).
CONCLUSION: Our results suggest that compared to the Fc fragment, RF titers were the more important risk factor in survival of anti-TNF drugs.

11. Evaluation of MMP-9, MMP-13, MMP-21, and TIMP-1 expressions in malign melanom, dysplastic nevi, and banal nevi
Meryem Yuvruk, Rabia Burcin Girgin, Ebru Zemheri
PMID: 38757103  PMCID: PMC11095330  doi: 10.14744/nci.2023.69009  Pages 158 - 166
OBJECTIVE: Although the role of MMPs in the pathogenesis of melanoma is known, few studies have investigated their role in the development of nevi and dysplastic nevi. This study aims to search the expression differences of MMP-9, MMP-13, MMP-21, and TIMP-1 between malignant melanoma (MM), intradermal nevi (IDN), and dysplastic nevi (DN).
METHODS: MMP-9, MMP-13, MMP-21, and TIMP-1 antibodies were studied immunohistochemically for 60 cases in our pathology clinic archive between 2013 and 2014.
RESULTS: The MM group had the highest expression percentage and intensity for MMP-9 (p<0.001). There was no statistical significance between MMP-13 expression intensities of lesion cells and stromal cells and stromal expression intensities (p>0.05). MMP-21 lesion staining intensities in DN and MM compared to IDN were statistically significant (p=0.001, p=0.011, respectively). For TIMP-1, there was a significant difference between the IDN and the MM group regarding the staining proportion of lesion cells (p<0.01). There was a statistically significant difference in all groups according to lesion cells’ expression intensity. (IDN-DN p<0.001, IDN-MM p=0.044, DN-MM p<0.001).
CONCLUSION: The following markers can be helpful when lesions cannot be differentiated; increased staining proportions and intensity of MMP-9 in both lesion and stromal cells favor MM in cases where MM and IDN cannot be differentiated. The increased MMP-13 staining proportion of lesion cells can favor DN in cases where the pathologist cannot differentiate DN and MM. Intense expression of MMP-21 by lesion cells can be a potential marker for evaluating the lesion in favor of DN in cases where DN and IDN cannot be differentiated. The high expression intensity of TIMP-1 in lesion cells can favor DN in cases where there is ambiguity between DN and MM. High expression proportion and intensity of stromal cells of TIMP-1 can be useable in favor of MM in cases where MM and DN cannot be differentiated.

CASE REPORT
12. A rare disease: ZAP70 deficiency
Seher Erdogan, Selen Ceren Cakmak, Gurkan Atay, Canan Hasbal Akkus, Burcu Karakayali, Ozlem Akgun Dogan, Betul Sozeri
PMID: 38757100  PMCID: PMC11095332  doi: 10.14744/nci.2022.89646  Pages 167 - 170
Zeta associated protein (ZAP) 70 deficiency is a rare disease. ZAP70 deficiency results in an autosomal recessive form of severe combined immunodeficiency (SCID) that is characterized by a selective absence of CD8 T cells. The diagnosis should be suspected in patients presenting with a severe combined immunodeficiency phenotype and selective deficiency of CD8 T cells. Sequencing of the ZAP70 gene can confirm the diagnosis. We wanted to emphasize that immunodeficiencies should also be remembered in the differential diagnosis by presenting a 5-month-old patient who applied to our clinic with complaints of skin rash and cough, was given respiratory support with mechanical ventilation for a long time, and was diagnosed with ZAP70 deficiency.

REVIEW
13. Bioinformatics approach for searching for natural products in vector-borne disease management
Rujittika Mungmunpuntipantip, Viroj Wiwanitkit
PMID: 38757105  PMCID: PMC11095338  doi: 10.14744/nci.2023.87523  Pages 171 - 176
Vector-borne disease is an important public health problem. This disease is common in tropical areas and affects millions of people. The control and management of disease is an important consideration. Effective treatment is important in management of patients infected with vector-borne disease. A common problem in therapeutic management of the patient is the lack of an effective drug. Therefore, it is necessary to find a new effective drug for managing vector-borne disease. To search for a new drug, new technologies are applicable. Bioinformatics technologies are useful in new drug search. Application of the bioinformatics technologies in new anti-vector-borne disease drug search is interesting. In this review, the author briefly discusses the use of bioinformatics technology in searching for natural products in vector-borne disease management. Concepts and examples of some important diseases are presented. (NCI-2023-3-6)

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