Nailfold capillaroscopy abnormalities and pulmonary hypertension in mixed connective tissue disease and systemic sclerosis patients.

OBJECTIVE: Pulmonary arterial hypertension (PAH) represents an important vascular complication of mixed connective tissue disease (MCTD) and systemic sclerosis (SSc). Microvascular involvement in these diseases can be investigated by means of nailfold capillaroscopy (NFC). Microvascular involvement detected in the nailfold bed is the mirror of the microvascular damage occurring in the entire body, further indicating the involvement of the target organs. The aim of this study was to evaluate the microvascular involvement in MCTD patients with or without PAH, compared to that found in SSc patients with or without PAH. PATIENTS AND METHODS: This cross-sectional study was performed in the Department of Internal Medicine and Department of Rheumatology, Timișoara, Romania, during the time period between January 2017 and December 2022, on a group of 26 patients with MCTD and 26 SSc patients. Antinuclear antibodies, anti-U1-RNP, anti-Scl 70, anti-centromere, anti-cardiolipin antibodies (aCL) (IgM, IgG), anti-ß2-glycoprotein I (aß2GPI) (IgM, IgG) antibodies, and lupus anticoagulant (LAC) were determined in both the groups. PAH was evaluated through cardiac ultrasonography, determining the sPAP (systolic pulmonary artery pressure). Nailfold capillaroscopy was performed using a USB Digital Microscope and 2.0-megapixel digital camera recording capillaries density, giant capillaries, enlarged capillaries, capillaries hemorrhages, avascular areas, ramified/bushy capillaries scores. Data were recorded and presented as mean ± standard deviation. Statistical analyses were performed using the Student's t-test, ANOVA test, and Pearson's correlation. Differences were considered statistically significant if p-value < 0.05. RESULTS: Among the MCTD patients, PAH was identified in 12 patients (46.15%), while among the SSc patients PAH was identified in 14 patients (53.84%). Development of PAH in MCTD patients was associated with lower capillaries density (p-value < 0.00001), higher scores of giant capillaries, ramified/bushy capillaries, and capillary hemorrhages (p-value < 0.00001, for each of them). Anti-U1-RNP, aCL, aß2GPI antibodies and LAC were also found to be involved in PAH-associated MCTD development. Unlike MCTD patients, SSc patients with PAH presented with lower capillaries density and ramified/bushy capillaries scores (p-value < 0.05). CONCLUSIONS: The MCTD patients who presented significant NFC abnormalities (especially active and late scleroderma-like capillaroscopic pattern) are prone to PAH development. Capillary density reduction is the most important factor associated with the occurrence of PAH. Differences in NFC findings (especially capillary density and ramified/bushy capillaries) were detected among patients with MCTD and SSc having PAH.

Prevention is better than cure: identifying and dealing with the key features involved in the prevention of gestational diabetes - A bird's eye view.

Gestational diabetes (GDM) is considered to be the most common metabolic problem of pregnancy, which, if not recognized and treated on time, can lead to devastating effects on both the mother's health and the health of the fetus and the newborns. Many studies have revealed that the children born of GDM mothers or grandmothers have higher chances of developing diabetes type I or type II later in their life. Early identification of risk factors can help prevent the appearance of severe GDM and its complications witnessed both in the child and the mother. Obesity is one of the major risk factors that should not be ignored, and obese females should first undergo weight reduction plans in case of planned pregnancies. Other risk factors include a family history of DM arterial hypertension, significant weight gain during pregnancy, short sleep duration, women's exposure to stressful environments, changes in alpha and beta microbiota, and air pollution. Proper care should be provided to females of reproductive age both before and during pregnancy to avoid complications. Awareness programs for healthy lifestyles and diets, oral hygiene maintenance guides, and regular health check-ups can all be considered as a key to a healthy society. Expanding the analysis of gut microbiota in individuals at a heightened risk of GDM can hold particular value, especially during the preconception phase. The alterations in gut microbiota can serve as crucial factors in enhancing lifestyle modifications prior to conception. Further studies are required in this direction to decrease the prevalence of GDM, and efficient measures should be implemented before the consequences appear.

Serum biomarkers predictive of cirrhosis in alcoholic liver disease as an alternative to ARFI-SW elastography.

OBJECTIVE: Aspartate aminotransferase to platelet ratio index (APRI) and fibrosis 4 (FIB-4) index are noninvasive biomarkers that evaluate liver stiffness in patients with chronic viral hepatitis and are able to detect advanced hepatic fibrosis and cirrhosis. However, their usefulness in alcoholic liver disease (ALD), when compared with Acoustic Radiation Force Impulse- Shear Wave (ARFI-SW) elastography, is debatable. PATIENTS AND METHODS: We sifted the files of all enrolled patients with ALD that were admitted to our Emergency hospital between January 2019 and December 2020. All patients had undergone ARFI-SW elastography, and APRI and FIB-4 scores were calculated. The performance of APRI and FIB-4 scores in the prediction of cirrhotic patients according to ARFI-SW elastography was evaluated. RESULTS: In total, 120 patients with ALD were evaluated. All of them were male and Caucasian, with a mean age of 55.54±12.4 years. The mean ARFI-SW elastography score was 1.57±0.7 m/s, the median APRI score was 0.68 (0.1-11.6) and the median FIB-4 score was 1.8 (0.2-19.4). Stages of liver fibrosis according to ARFI-SW elastography were evaluated as F0-1 in 21 (10.5%), F2 in 35 (26%), F3 in 52 (17.5%), and F4 in 92 (46%) patients. Based on ARFI-SW elastography fibrosis stage classification, we estimated the optimal APRI and FIB-4 scores to predict the presence of liver cirrhosis (F4) by using ROC curve analysis and the Youden index. The optimal APRI score for F4 patients was calculated as >1.52 [area under the curve (AUC) 0.875, 95% CI 0.809-0.919; p<0.001], giving sensitivity (Se) 81.2%, specificity (Sp) 81.4%, positive predictive value (PPV) 76%, and negative predictive value (NPV) 86.1%. The optimal FIB-4 score for F4 patients was calculated as >2.77 (AUC 0.916, 95% CI 0.814-0.922; p<0.001), giving Se 83.8%, Sp 77%, 81.4 77%, and NPV 84.3%. CONCLUSIONS: APRI and FIB-4 scores can be used as screening tools in ALD for predicting cirrhosis instead of ARFI-SW elastography measurement, which is neither widely available nor an affordable method. Additional prospective studies are required in the future to confirm this finding.

Ventricular-arterial coupling assessed by PWV/GLS ratio in hypertensive patients.

OBJECTIVE: The physiological interaction between the left ventricle (LV) and the arterial system, defined as ventricular-arterial coupling (VAC), facilitates the optimal volume of cardiac work and cardiovascular performance. The aim of this study was to evaluate the benefit of PWV/GLS ratio associated with other vascular and cardiac performance parameters in hypertensive patients compared to age-matched healthy controls. PATIENTS AND METHODS: We calculated the ratio of pulse wave velocity (PWV), as a marker of arterial stiffness, to global longitudinal strain (GLS), as a marker of left ventricular function in 135 patients divided in 3 groups, as follows: group 1 (HT + CAD) enrolled 54 hypertensive patients with coronary artery disease, group 2 (HT) enrolled 43 hypertensive patients and group 3 (CON) represented the control group consisting of 38 age-matched healthy subjects. RESULTS: GLS values were significantly reduced in HT+CAD (-17.50±7.2) vs. HT (-17.95±5.3) vs. control (-20.13±4.6) (p-value <0.001). PWV values were higher in HT+CAD (9.90±3.1) and HT (9.70±2.5) vs. control (7.85±3.2) (p-value <0.001). VA coupling measured by the PWV/GLS ratio showed significantly lower values in HT+CAD and HT vs. control (p-value <0.001). The ROC curve identified a threshold of -0.054 of the PWV/GLS ratio to detect altered ventricular-arterial coupling AUROC = 0.836, 95% CI [0.762; 0.909]. CONCLUSIONS: This study demonstrated that assessment of the PWV/GLS ratio represents a useful tool to detect altered ventricular-arterial coupling in hypertensive patients. The perspectives of future use could include monitoring of earlier development of multiple organ damage in hypertensive patients and the efficacy of the different hypertensive medications. Extensive prospective studies are needed to confirm this hypothesis.

Endothelial dysfunction in psoriatic arthritis patients: correlations between insulin resistance and disease activity.

OBJECTIVE: Cardiovascular atherosclerotic comorbidities represent an important cause of morbidity and mortality in patients diagnosed with psoriatic arthritis. In both atherosclerosis and Psoriatic arthritis, inflammation plays a pivotal role. Psoriatic arthritis is considered as an independent risk factor for the development of atherosclerosis with accelerated evolution. Development of atherosclerosis is initiated by the endothelial cell dysfunction along with inflammation and insulin resistance. The main aim of the study was to evaluate the endothelial function in Psoriatic arthritis patients, and to identify if it is related to the insulin resistance and Psoriatic arthritis disease activity. PATIENTS AND METHODS: In this case-control study, a group of 32 age and gender matched healthy controls was formed and compared to the group of 32 Psoriatic arthritis patients. We assessed the following parameters: Disease Activity in Psoriatic Arthritis Score, Homeostatic Model Assessment for Insulin Resistance, serum levels of the tumor necrosis factor alpha (TNFα), and the endothelial dysfunction by means of the flow-mediated dilation at brachial artery. The Student's t-test, the Pearson correlation and the ANOVA test were used to perform the statistical analysis of the data obtained; p-value <0.05 was considered as statistically significant. RESULTS: Compared to the patients in the control group, TNFα and Homeostatic Model Assessment for Insulin Resistance were increased (p-value <0.001), and flow-mediated dilation at brachial artery was decreased (p-value <0.001) in the disease group. In Psoriatic arthritis patients, significant correlations were found between Disease Activity in Psoriatic Arthritis Score and Homeostatic Model Assessment for Insulin Resistance (r=0.8143, p-value <0.001), and between Disease Activity in Psoriatic Arthritis Score and flow-mediated dilation at brachial artery % (r= -0.8376, p-value <0.001). Psoriatic arthritis patients treated with Methotrexate exhibited reduced values of Disease Activity in Psoriatic Arthritis Score and Homeostatic Model Assessment for Insulin Resistance and increased values of flow-mediated dilation at brachial artery, when compared with the untreated patients. CONCLUSIONS: Endothelial dysfunction is present in Psoriatic arthritis patients and has a significant correlation with both, the course of the disease and the insulin resistance.

Chest wall deformities and their possible associations with different genetic syndromes.

OBJECTIVE: Our primary objective was to identify discrete and syndromic cases of Pectus excavatum (PE) and Pectus carinatum (PC). We also intended to highlight the significance of further genetic exploration in clinically suspected syndromic cases of PC and PE. Pectus excavatum (PE) and Pectus carinatum (PC) are the most common morphological chest wall deformities. Although various hypotheses have been put forth, the pathogenesis of both entities is largely unknown. Clinicians often refer such cases for further genetic evaluation to exclude an associated underlying connective tissue disorder or a syndrome. Additionally, a detailed anamnesis with focused family history and thorough dysmorphological physical examination was done. PE and PC are considered isolated abnormalities if there is the absence of features of other syndromes, eliminating the need for further genetic evaluations. It is believed that the pattern of inheritance of these non-syndromic isolated PE and PC cases with positive family history could be multifactorial in nature. The recurrence risk of such isolated cases is thought to be low. Further diagnostic studies are indicated as PE and PC could be a part of a syndrome. Among the many syndromes, the most common monogenic syndromes associated with PE and PC are Marfan's and Noonan's. PATIENTS AND METHODS: After obtaining the consent, we compiled a database of the patients who presented with chest wall deformities during the period 2017-2019. We selected 70 cases with PC and PE deformities to identify the discrete and syndromic PC and PE cases. During the study, we perused the cytogenetic and/or molecular analyses, that had been conducted to confirm the clinically suspected syndromic cases. We also scrutinized for the presence of PC and PE cases that are associated with the rare syndrome (s). RESULTS: Various genetic abnormalities were identified in 28 (40%) of the 70 cases that had been diagnosed with chest wall abnormalities. Along with PE and PC, other thoracic wall abnormalities were also identified, such as the broad chest, bell-shaped thorax, and elongated or enlarged thorax. One case of a rare genetic disorder of Morquio syndrome associated with PC was also identified. Novel (previously unpublished) genomic variants are reported here. CONCLUSIONS: It is important to delve deeper when encountering cases of PE and PC by conducting a further genetic exploration of such cases to identify syndromic associations that cause other structural and functional disorders, diagnosis of which might be missed during the early developmental period. Early identification of such disorders may help us correcting the defects, slowing the progression of disease processes, and preparing better to deal with the potential outcome.

Fecal calprotectin - a valuable predictor of microscopic colitis.

OBJECTIVE: Microscopic colitis (MC) has been of major concern worldwide due to its relapsing and remitting nature of chronic diarrhea. Quality of life of patients suffering from this disease is quite debilitating. PATIENTS AND METHODS: In order to understand the role and importance of fecal calprotectin (FC) we performed a statistical analysis on the patients suffering from chronic diarrhea and admitted to our hospital from 2014 to 2020, and who were prescribed Loperamide (Imodium) or Budesonide or a combination of both and had undergone FC detection test. RESULTS: FC was found to be significantly correlated to the age, alcohol consumption and beta blocker use. A high level of the FC concentrations increases the chances of having flare-ups of diarrhea episodes making the quality of life of such patients worse. CONCLUSIONS: FC concentrations should be monitored frequently and precautionary measures to avoid a relapse should be aimed. Measures to improve quality of life, should be of prime concern. In-depth research is required to better understand MC and to find better treatment options which can be used on a long-term basis, instead of anti-motility drugs which are able to control the acute episodes, but when discontinued result in an increased tendency to have relapses.

The preoperative evaluation of post-COVID-19 patients scheduled for elective surgery - What is important not to miss!

Continuous rise in the number of COVID-19 cases, since it was first diagnosed in 2019, forced the entire medical fraternity to delay elective surgeries. The preoperative evaluation guidelines that were used in the pre-COVID-19 era underwent significant changes, adding modifications to meet the post-COVID patients' specific criteria and requirements. Currently, all patients before or at the time of hospital admission were tested using a nasopharyngeal swab, by RT-PCR for SARS-CoV-2. Apart from this, for a patient undergoing elective surgery in their post-COVID-19 period, it is mandatory to obtain a detailed history of COVID-19 disease/SARS-CoV-2 infection, to identify residual symptoms or any organ dysfunction the infection might have caused. As well as the functional optimization of the patient to achieve the best clinical and biological status before the surgery. After all the systems have been thoroughly investigated, the risk-benefit ratio needs to be calculated, keeping in mind the cytokine storm and inflammatory responses encountered postoperatively. A mere negative RT-PCR test cannot be considered as the only decisive factor to operate, as the post-COVID-19 phase can influence postoperative outcome of the patient. Hence, the pre-operative evaluation protocols of post-COVID patients should be set and followed thoroughly, in order to avoid post-surgical complications. For better surgical and post-surgical management of post-COVID-19 patients, conducting clinical tests, assessing previously administered medications, evaluating the need for deep venous thrombosis prophylaxes, and identifying subclinical inflammatory state are the measures that should be taken.

Implication of wide surgical excision in minimizing positive margins and consequential secondary excision - a retrospective comparative study involving 106 basal cell carcinoma cases.

OBJECTIVE: The use of current surgical techniques in the management of skin cancers that are not amenable to other treatment options has become the cornerstone of dermatological surgical intervention. Among the many benign lesions and malignant lesions, such as squamous cell carcinomas, melanomas, and Merkel cell carcinomas, the tumors that are commonly excised surgically are the basal cell carcinomas (BCC). Although the majority of BCC lesions spread locally and are rarely metastatic, these lesions may recur, especially, if the excised tissue consists of positive surgical margins. As BCC lesions are more common on the head, face, and neck regions, inadvertent positive margin excisions to help avoid major disfigurement of the regions may contribute to their recurrence. Trichoepithelioma (TE) is a benign tumor that bears a close resemblance to BCC, and therefore, clinicians encounter difficulty in differentiating between TE and BCC lesions. Clinicians have to rely on histopathology and immune-histochemical markers to rule out TE. This differentiation is crucial to make a definitive diagnosis of BCC and subsequently, employ a more aggressive surgical excision approach to treat this invasive tumor as compared with TE. Our focus in this article is to highlight only the surgical excision management of local and or locally invasive BCCs and report the success rate of our hospital's Dermato-venereology clinic (DVC) in Timisoara, Romania. This article highlights the role of an appropriate wide local lesion excision (5 mm) with negative surgical margins in the prevention of further surgical interventions, be it for corrective or esthetic reasons. PATIENTS AND METHODS: This is a retrospective study that summarizes the evaluation of 120 lesions from 106 patients who were treated for BCCs at DVC (University Hospital), using a wide surgical excision method.  Following the Romanian Society of Dermatologists guidelines, local non-aggressive BCC lesions were excised with margins of 5 mm and up to 1 cm for the aggressive sclerosing subtype. RESULTS: The results of the audit of a sample of 120 lesions from 106 patients demonstrated that none of the surgically treated patients had recurrences and only 23 (19.16%) had positive surgical margin lesions. Out of these, 17 (73.91%) lesions underwent second surgical excision, while only three (13.04%) showed the presence of a residual tumor. The evaluation results may encourage dermatologists worldwide to make appropriately sized excision, especially in regions other than the head and neck, to avoid positive surgical margins and eliminate the need for consequent surgery. CONCLUSIONS: For a better post-surgical prognosis of BCC, the authors recommend the practice of a wide margin excision (5 mm) during the primary surgery to avoid secondary surgery, especially if the tissue in the region is not sparse and chances of causing major disfigurement are minimal. As our findings suggest, only a few cases have the presence of residual tumor in the second surgery, hence authors also advocate the necessity to inform the patients about the merits of a second surgery, clearly mentioning the possibility of the absence of tumor even in the presence of positive margin.

Selecting the right anticoagulant for stroke prevention in atrial fibrillation.

OBJECTIVE: The embolization of thrombi formed within the atria can occur in any form of atrial fibrillation (AF), i.e., paroxysmal, persistent, or permanent. Although ischemic stroke is the most frequent embolic event associated with AF, embolization to other sites in the pulmonary and systemic circulations may occasionally occur. To avert the risk of embolization, long-term oral anticoagulation therapy is recommended for all AF patients if the CHA2DS2-VASC score is at least 1 for men and at least 2 for women. Since anticoagulant therapy is associated with an increased risk of bleeding, the choice of oral anticoagulant agent should be made by careful consideration of the benefit-to-risk ratio. The use of a newer class of direct oral anticoagulants (DOACs) as an alternative to the anti-vitamin K (AVK) anticoagulants (warfarin, acenocumarol, etc.) can help mitigate the need for periodic monitoring of International Normalized Ratio (INR) and adverse bleeding events that are commonly associated with the use of AVK anticoagulants. Though the use of DOACs (dabigatran, rivaroxaban, edoxaban, apixaban, etc.) is gaining ground due to their relative safety profile and the low overall cost, quite a few clinicians remain skeptical about their use. PATIENTS AND METHODS: Our objective was to evaluate the risk of thromboembolism, stroke, neuropsychiatric illness, depression, and dementia, in patients with non-valvular atrial fibrillation who have been treated with either acenocumarol or apixaban, as well as to see the inflammatory status (ESR) and levels of fibrinogen. Our team at Municipal Emergency University Hospital, Timisoara, Romania, conducted a retrospective study using the medical records of AF patients who were treated with either apixaban or acenocumarol between 2016-2019. We divided the patients into two groups and compared the groups for the aforementioned outcomes. RESULTS: AF patients who were prescribed apixaban had a lower rate of stroke and psychiatric illness compared to those on acenocumarol. No significant correlation was found in terms of risk of developing depression or dementia between the groups. CONCLUSIONS: Non-valvular AF patients on apixaban had lower rates of thromboembolic events than the patients on acenocumarol. This article will serve as a reminder of the positive health and financial outcomes of apixaban use, especially to those healthcare systems that are still oblivious to the decrease in economic burden and gain in quality-adjusted life years (QALY) by the long-term use of NOACS/ DOACS instead of the AVK anticoagulants.