Clinical and Demographic Characteristics of Herpetic Keratitis Patients-Tertiary Centre Experience.

Background and Objectives: Herpes simplex keratitis (HSK) is the leading infectious cause of corneal damage and associated loss of visual acuity. Because of its frequent recurrence, it represents a major health problem; thus, timely and accurate diagnosis is the key to successful treatment. To enable this, we aimed to determine HSK patients' demographic and clinical features. Materials and Methods: This prospective study included 55 patients diagnosed with HSK between March 2019 and August 2022 at the Department of Ophthalmology, Clinical Hospital Rijeka. Results: We found that HSK is most prevalent in the elderly, with 72.73% of patients older than 60. The most common HSK types were dendritic (HSK-D; 43.64%) and stromal with epithelial ulceration (HSK-SEU 23.64%). HSK recurrences occurred in 65.45% of patients, with most having two to five recurrences (55.56%). Visual acuity at presentation (65.5%) and after treatment (50.9%) was mostly in the 20/50 range. The longest period until the disease symptoms were resolved was in the group with stromal HSK without epithelial ulceration (HSK-SnEU), for which symptoms lasted more than 11 weeks in 87.5% of patients. The overall incidence of HSK-related complications was high (85.45%), with 76.4% of patients having corneal scarring. The average time from symptom to treatment was 15.78 days. Interestingly, we observed a strong seasonality in the incidence of HSK, which was most prevalent in the colder months, with 63.6% of cases occurring between October and March. Conclusions: To the best of our knowledge, this is the first prospective study in Croatia, and one of the few in Europe, to describe the demographic and clinical features of HSK patients. We found that HSK is most common in the elderly population, with its dendritic form as a clinical presentation. We have shown that HSK is prone to recurrence and secondary complications, with a worryingly long time between symptom and treatment, indicating the need for diagnostic testing in routine practice.

Use of CPAP Ventilation in Non-ICU Wards May Influence Outcomes in Patients with Severe Respiratory COVID-19.

Background and Objectives: The COVID-19 disease has significantly burdened the healthcare system, including all units of severe patient treatment. Non-intensive care units were established to rationalize the capacity within the Intensive Care Unit (ICU) and to create a unit where patients with Acute Respiratory Distress Syndrome (ARDS) could be treated with non-invasive Continuous Positive Air Pressure (CPAP) outside the ICU. This unicentric retrospective study aimed to assess the efficacy of NIV Treatment in Patients of the fourth pandemic wave and how its application affects the frequency and mortality of ICU-treated patients at University Hospital Rijeka compared to earlier waves of the COVID-19 pandemic. Furthermore, the study showcases the effect of the Patient/Nurse ratio (P/N ratio) on overall mortality in the ICU. Materials and Methods: The study was conducted on two groups of patients with respiratory insufficiency in the second and third pandemic waves, treated in the COVID Respiratory Centre (CRC) (153 patients). We also reviewed a cohort of patients from the fourth pandemic wave who were initially hospitalized in a COVID-6 non-intensive unit from 1 October 2021 to 1 November 2022 (102 patients), and some of them escalated to CRC. Results: The introduction of the CPAP non-invasive ventilation method as a means of hypoxic respiratory failure treatment in non-intensive care units has decreased the strain, overall number of admissions, and CRC patient mortality. The overall fourth wave mortality was 29.4%, compared to the 58.2% overall mortality of the second and third waves. Conclusions: As a result, this has decreased CRC patient admissions and, by itself, overall mortality.

Clinical Dilemmas in the Treatment of Elderly Patients Suffering from Hodgkin Lymphoma: A Review.

Elderly patients make up a significant number of cases of newly diagnosed Hodgkin lymphoma. However, unlike in young patients, the outcomes of elderly patients are poor, and they are under-represented in phase III trials. Prior to treatment initiation, geriatric assessment should ideally be performed to address the patient's fitness and decide whether to pursue a curative or palliative approach. The ABVD regimen is poorly tolerated in unfit patients, with high treatment-related mortality. Alternative chemotherapy approaches have been explored, with mixed results obtained concerning their feasibility and toxicity in phase II trials. The introduction of brentuximab vedotin-based regimens led to a paradigm shift in first- and further-line treatment of elderly Hodgkin lymphoma patients, providing adequate disease control within a broader patient population. As far as checkpoint inhibitors are concerned, we are only just beginning to understand the role in the treatment of this population. In relapsed/refractory settings there are few options, ranging from autologous stem cell transplantation in selected patients to pembrolizumab, but unfortunately, palliative care is the most common modality. Importantly, published studies are frequently burdened with numerous biases (such as low numbers of patients, selection bias and lack of geriatric assessment), leading to low level of evidence. Furthermore, there are few ongoing studies on this topic. Thus, elderly Hodgkin lymphoma patients are hard to treat and represent an unmet need in hematologic oncology. In conclusion, treatment needs to be personalized and tailored on a case-by-case basis. In this article, we outline treatment options for elderly Hodgkin lymphoma patients.

Improvement in the outcomes of mantle cell lymphoma in the last decade: a real-life non interventional study of the Croatian Cooperative Group for Hematologic Diseases.

AIM: To compare the outcomes of Croatian patients with mantle cell lymphoma (MCL) who started treatment in 2007 and 2008 (historical cohort) and of those who started treatment between 2015 and 2017 (recent cohort). METHODS: The historical cohort consisted of 40 patients who started treatment with rituximab in 2007 and 2008. Data on the recent cohort, consisting of 89 patients, were collected retrospectively from the electronic databases of Croatian hospitals with hematology units. Demographic characteristics and data on induction regimens, autologous stem cell transplantation (ASCT), and rituximab maintenance in the first remission, event-free survival (EFS), and overall survival (OS) were available for both cohorts, and data on cell morphology, mantle cell international prognostic index (MIPI), and Ki67 expression only for the recent cohort. RESULTS: The recent cohort had significantly better two-year EFS and OS (EFS 58% vs 40%, P=0.014; OS 80% vs 56%, P=0.009), especially in patients below 65. In univariate analysis, induction regimen, ASCT, and maintenance were significant prognostic factors for EFS and the former two for OS. In the multivariate analysis, only ASCT remained significant. Bendamustine+rituximab (BR) induction improved the outcomes of non-transplantable patients over R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, steroid). Blastoid morphology and high MIPI were adverse prognostic factors for EFS and OS. CONCLUSION: In the last decade, the outcome of newly diagnosed MCL patients improved. ASCT in the first remission was the main contributor in transplantable patients and BR in non-transplantable. Regularly updated national guidelines may help in a timely adoption of new treatments, thus improving the results.

Small intestinal bacterial overgrowth and non-alcoholic fatty liver disease diagnosed by transient elastography and liver biopsy.

BACKGROUND: We aimed to determine if there was a higher incidence of small intestinal bacterial overgrowth (SIBO) in non-alcoholic fatty liver disease (NAFLD) than in patients without NAFLD. Moreover, we assessed whether patients with significant fibrosis (SF) had a higher incidence of SIBO compared with patients with non-significant or no liver fibrosis. METHODS: NAFLD was diagnosed in 117 patients by using Fibroscan with a controlled attenuation parameter (CAP) as well as liver biopsy (LB). SIBO was defined by esophagogastroduodenoscopy with an aspiration of the descending duodenum. RESULTS: Patients with non-alcoholic steatohepatitis (NASH) and those with SF on LB had a significantly higher incidence of SIBO than patients without NASH and those without SF, respectively (P < .05). According to histological characteristics, there was a higher proportion of patients in the SIBO group with higher steatosis and fibrosis grade, lobular and portal inflammation, and ballooning grade (P < .001). In multivariate analysis, significant predictors associated with SF and NASH were type 2 diabetes mellitus (T2DM) and SIBO. Moreover, in multivariate analysis, significant predictors that were independently associated with SIBO were T2DM, fibrosis stage and ballooning grade (OR 8.80 (2.07-37.37), 2.50 (1.16-5.37) and 27.6 (6.41-119), respectively). The most commonly isolated were gram-negative bacteria, predominantly Escherichia coli and Klebsiella pneumoniae. CONCLUSION: In this relatively large population of patients, we used a gold standard for both SIBO (quantitative culture of duodenum's descending part aspirate) and NAFLD (LB), and we demonstrated that NASH patients and those with SF had a higher incidence of SIBO. Moreover, significant predictors independently associated with SIBO were T2DM, fibrosis stage and ballooning grade. Although TE is a well-investigated method for steatosis and fibrosis detection, in our study, independent predictors of SIBO were histological characteristics of NAFLD, while elastographic parameters did not reach statistical significance.

Accuracy of Controlled Attenuation Parameter and Liver Stiffness Measurement in Patients with Non-alcoholic Fatty Liver Disease.

We evaluated the diagnostic accuracy of the controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) measured with either an M or XL probe against liver biopsy (LB) in patients with non-alcoholic fatty liver disease (NAFLD). This study was a cross-sectional prospective study that included 179 NAFLD patients. With a cutoff value for CAP ≥345, we can exclude significant steatosis in 87% (79.4%-92.5%) of our population. With respect to the LSM, the highest accuracy was obtained for F ≥ F3 (area under the receiver operating characteristic curve [AUROC] = 0.98) and F = F4 (AUROC = 0.98). In a multivariable linear regression model, significant predictors influencing LSM were fibrosis stage (ß = 2.6, p < 0.001) as a positive predictor and lobular inflammation (ß = -0.68, p = 0.04) as a negative predictor, without significant influence after adjustment for CAP and probe type. We found that CAP is a satisfactory method for excluding advanced steatosis, while LSM is a good non-invasive marker for the exclusion of fibrosis.

How could analyzing the activity of two matrix metalloproteinases unveil the cause of sudden cardiac death.

Sudden cardiac death is natural, unexpected death, related to cardiovascular disease. Its postmortem elucidation is significant, as the family of the deceased aspires to prevent other sudden deaths. Irrespective of the proper etiological entity, the myocardial collagen matrix remodels, associated with the progression of cardiovascular diseases. It has become evident that many mediators such as humoral factors, transforming growth factor (TGF)-ß1 among them, are involved in the remodeling process. Cardiac remodeling is the balance of regenerative and eliminatory processes that include enzymes involved in the degradation of extracellular matrix (ECM) components. Enzymes capable of degrading native fibrillar collagen are interstitial collagenases, specifically matrix metalloproteinases (MMP)-1 and MMP-8. Here, we suggest a technique of visualizing turnover of collagen in cardiac tissue.

Putative hormone with anti-obesogenic and insulin-sensitizing effect.

It was confirmed that bone morphogenetic protein-9 (BMP-9), like insulin, improves glycemia in diabetic mice and regulates glucose metabolism in hepatocytes, which is why it is proposed as a candidate for the hepatic insulin-sensitizing substance (HISS). Regarding the fact that BMP-9 has a signaling pathway similar to other BMPs as well as insulin, it is expected that BMP-9 would also have certain effects on the liver. In our 2011 hypothesis, we aimed towards BMP-9 as a possible "hepatic insulin-sensitizing substance" (HISS) and in this article, we provide further evidence, derived from existing studies, suggesting that this putative hormone might in fact be none other than BMP-9.

Is the term "fasciculus opticus cerebralis" more justifiable than the term "optic nerve"?

The terminology of the optic nerve had already been changed three times, since 1895 until 1955 when the term "nervus opticus" was introduced in the "Terminologia Anatomica". Following our study we claim that, from the aspect of phylogenetic evolution of binocular vision development as well as optical embryogenesis where opticus is evidently presented as a product of diencephalic structures, the addition of the term "nervus" to opticus is not adequate and justified. From the clinical aspect the term "nervus opticus" is also inadequate, both as a "nerve" that has no functional regenerative properties, unlike other cranial nerves, as well as from a pedagogical and didactical aspect of educating future physicians. We suggest that the term "Fasciculus Opticus Cerebralis" should be used as it much better explains the origin as well as its affiliation to the central nervous system.

Refractive errors in children of Primorsko-Goranska County--epidemiological study.

Three institutions: Teaching Institute of Public Health of Primorsko-Goranska County, Croatian Association "Albert Einstein" and Eye Clinic "Dr B.Vojnikovid" Rijeka agreed a five-year project to study children's health status of vision at Primorsko-Goranska County. Main task was the study of damage of vision in children due to prolonged sun exposure. Examination were conducted on a three locations, with the assumption of varying insolation: Island of Rab, Novi Vinodolski and Delnice. The study included children aged between 9 to 14 years. The study included 189 children. Except routine ophthalmologic examinations in addition were preformed biomicroscopic examination of the anterior segment of the eye, intraocular pressure and eye fundus. In a certain number of children with suspect of a specific disease (macular degeneration, glaucoma and refractive error), additional tests were performed: glaucoma treatment, field of vision, optical coherence tomography (OCT) of the eye and detailed eye refraction. This study specifically addressed of refractive error at that three different regions. It was found that the most difficult situation was at the Novi Vinodolski where as many as 40% of children have a refractive error, followed by Island of Rab with 17% and Delnice with 9%. Especially like to mention that on the island of Rab, 50-60 years ago, it was a very rare occurrence of some refractive errors in children.

Predicting carotid restenosis by comparison of plaque MCP-1 mRNA expression and serum levels.

As cardiovascular pathology grows in numbers, research into the discovery of new chemokine biomarkers should not be neglected, as they seem to be paramount in atherosclerosis prevention and its early detection. Chemokines attract and activate leukocytes and are well recognized in the environment of inflammatory response. MCP-1 is a valuable chemokine whose potential to become a new crucial atherosclerosis marker is surely worth investigating. Since quantities of MCP-1 found in lesions are as low as immeasurable, we propose the use of an immunohistochemical method for the quantification of MCP-1 levels in atherosclerotic lesions. Additionally, serum levels of MCP-1 can be measured by commercially available immunoassays. Proposed MCP-1 concentration increase may explain the acceleration in lesion's atherosclerosis progression as chemokine activation occurs once they bind to specific ligands. If proven, this hypothesis would indicate the need for further studies in order to objectively link the increased MCP-1 expression with carotid restenosis.

Significance of mini radial endoscope ultrasound (MREUS) in diagnosis and therapy of colorectal neoplasia.

In the pursuit to advance diagnostic procedures with colon carcinoma patients, we included the 15 MHz mini radial endoscopic ultrasound (MREUS) in our work up algorithm, following PH verification. When compared to surgical and final pathohistological (PH) findings, MREUS shows that it can differentiate colon layers in great detail and therefore we can determine the degree of carcinoma dissemination (T1, T2, T3, T4) as well as to make a correct therapeutic choice. MREUS (12-15-20 MHz) is a highly reliable colon layer structural analysis method. As we have shown in our study, the accuracy of T stage colon carcinoma visualization in correlation to equivalent PH studies varies from 90-100% which makes MREUS the best as well as the most reliable method in determining preoperative T stage colon carcinoma.

Basics of voice dysfunction--etiology and prevention of voice damage.

Voice is one of the most important means of communication and as such should be taken care of. The etiology of voice disorders is diverse. Due to the development of the society we live in, way of life, environmental factors, and exposure to pharmacological agents as well as demands we make towards our voice, there is a substantial growth in the number of people with voice disorders. We tasked ourselves to find out if it is possible to enlighten people on the importance of voice, to motivate them to take care of it, to notice the changes in its quality and eventually ask for help. We assessed in which measure do we understand the importance of a healthy voice, and do we know which is the most important factor that adds to its decline. For a long number of years voice therapists and other experts in the voice disorder field have been discussing the optimal voice impostation as well as vocal exercises and methods behind voice recovery. They have all come to the same conclusion that phonation is dependant on the sort of the voice disorder and the patient motivation. We wanted to go one step further and investigate, dependence of voice quality and the damage etiology (organic - functional), which are the predominant causes, what are the factors that account for the damage and how the disorder motivates the patient and therefore influences the rehabilitation success rate.

Clinical and medicolegal characteristics of neck injuries.

The predominance in performing surgery of major spine injuries by neurosurgeons usually has the consequence of treating all types of spine injuries by neurosurgeons - neurotraumatologists. In the neurosurgical wards of Clinical Hospital Rijeka, we take care of the majority of these patients, following both the major, as well as minor--whiplash injuries of the neck. This article is an overview of the patients admitted in the one year period (October 1st 2009-October 1st 2010) where 1077 cases of neck injuries were analyzed. Vast majority of these injuries were due to traffic accidents (over 94%), and only a small proportion were serious injuries that needed a surgical approach--decompression and stabilization (c1%). We analyzed minor neck injuries thoroughly both because of the increasing number of whiplash neck injuries and because more complicated diagnostic and therapeutic protocols occupy too much time in the ambulatory practice of our neurotraumatologists each year thus representing a growing financial burden to the health organizations and to the society as a whole. Our results proved that the majority of the injured are male (over 60%), young and active (almost two thirds 21-40 years of age), had commonly sustained a Quebec Task Force (QTF) injury of grades 2 and 3 (almost 90%), and, if properly treated, recovered completely after a mean therapy period of ten weeks. Only a minority complained of prolonged residual symptoms, some of them connected with medico-legal issues (less than 20%). The results shown are in contrast with the general opinion that malingerers in search of financial compensation prevail in these cases, and leads to the conclusion that minor neck injuries (including whiplash) as well as Whiplash Associated Disorder (WAD) are real traumatological entities, that have to be seriously dealt with.