Tom 57 (2019): Zeszyt 3 (September 2019)

Obesity is a growing health burden worldwide, increasing the risk for several diseases featuring the metabolic syndrome – type 2 diabetes mellitus, dyslipidemia, non-alcoholic fatty liver disease and cardiovascular diseases. With the increasing epidemic of obesity, a new pathologic condition has emerged as a component of the metabolic syndrome – that of non-alcoholic fatty pancreas disease (NAFPD). Similar to non-alcoholic fatty liver disease (NAFLD), NAFPD comprises a wide spectrum of disease – from deposition of fat in the pancreas – fatty pancreas, to pancreatic inflammation and possibly pancreatic fibrosis. In contrast with NAFLD, diagnostic evaluation of NAFPD is less standardized, consisting mostly in imaging methods. Also the natural evolution of NAFPD and its association with pancreatic cancer is much less studied. Not least, the clinical consequences of NAFPD remain largely presumptions and knowledge about its metabolic impact is limited. This review will cover epidemiology, pathogenesis, diagnostic evaluation tools and treatment options for NAFPD, with focus on practices for clinicians.

A significant workforce shortage of urologists available to serve the US population has been projected to occur over the next decade. Accordingly, much of the management of urologic patients will need to be assumed by other specialties and practitioners. Since primary care physicians are often first evaluate common urologic complaints, it makes sense that these physicians are in an excellent position to intervene in the management of these patients when appropriate. One of the most common complaints in urology is voiding dysfunction. The incidence of voiding dysfunction increases with age, with conservative estimates showing that over 50% of elderly patients suffer. Despite this high prevalence and its negative impact on quality of life, however, few seek or receive treatment, as many do not readily disclose these impactful yet personal symptoms. We sought to summarize the typical presentation, evaluation, assessment and therapeutic options for both male and female patients presenting with voiding dysfunction.

Introduction. Liraglutide (L) is the analogue of human glucagon-like peptide 1 which stimulates glucose-dependent insulin secretion and can modify the level of inflammatory biomarkers.

L can influence NF-kB inflammatory cascade, but the mechanisms of anti-inflammatory activities of L remain to be determined. In animal models L influenced an activity of Sirtuin 1(SIRT1). Moreover, recent evidences strongly suggest that SIRT1 up-regulation may serve as a potent therapeutic approach against development and progression of diabetic complications. The aim of this study was to investigate L effects directed on the pro-inflammatory NF-kB pathway and expression of SIRT1 in obese patients with type 2 diabetes mellitus (DM).

Materials and Methods. 15 obese patients with type 2 diabetes were studied, all using metformin (1-2 g/day) and sulfonylurea (glimiperide). All patients received L 1.2 mg daily add-on to stable therapy for 6 weeks. Blood samples were collected before, 6 weeks after start of treatment and after an overnight fast 6 weeks after stopping L, mononuclear cells (MNC) were isolated. The mRNA expressions of TNF-α, TLR2, TLR4, NOD1, IL-2 and SIRT1 were measured in MNC by RT-PCR. Ceruloplasmin concentration was measured in plasma by photometric method.

Results. In this add-on pilot clinical investigation we received new data that L can inhibit proinflammatory NF-kB pathway by increased SIRT1 expression in obese patients with type 2 DM improving metabolic profile. The mRNA expression in MNC of TNF-α, IkB, TLR2, TLR4, and plasma ceruloplasmin fell after 6 weeks of L. Expressions of IL-2 and NOD-1 were stable. There was a significant increase of SIRT1 mRNA expression. The mRNA expression in MNC of TNF-α, IkB, TLR2, TLR4, NOD1, SIRT1 and ceruloplasmin concentrations did not reverse to baseline levels after 6 weeks stopping of L treatment. IL-2 expression decreased in comparison with basic level.

Conclusions. L has a potent anti-inflammatory effect as do GLP-1 agonists due to inhibition of NF-kB pathways and up-regulate SIRT1 expression, down-regulating pro-inflammatory factors including cytokines (TNF-α), extra- and intracellular receptors (TLR2, TLR4), and inflammation markers such as ceruloplasmin. Long lasting effects of L can be mediated by epigenetic regulation of NF-kB pathway by SIRT-1.

Introduction. Several diagnoses have been associated with leukemoid reaction (LR). In patients with LR the diagnostic and prognostic value of detailed manual blood smear counts (such as the percentage of band cells or grading of neutrophil toxic changes) has not been studied previously.

Methods. We prospectively recorded all hospitalized adult (> 18 years old) patients with LR (≥ 30000/ul) of neutrophilic predominance, excluding patients with pre-existing leukocytosis due to hematological malignancies. We examined the diagnoses and prognosis (in-hospital mortality and post-discharge mortality up to a year after the end of the study) of these patients as well as the value of manual peripheral smear review.

Results. We recorded a total of 93 patients with LR from January 2017 to December 2017. Infection was the most common diagnosis (70%), followed by malignancy (7.5%) and bleeding (6.5%). In-hospital mortality (45%) and post-discharge mortality (35% of those discharged) were very high. Among blood smear findings, only neutrophil vacuolation was significantly more common in patients with infections (34%), although it was also observed in many patients without any infection (13%). Blood smear findings were not associated with prognosis.

Conclusion. Detailed manual smear review is a labor-intensive procedure and it has limited diagnostic and prognostic value in unselected hospitalized patients with neutrophilic LR.

Introduction. The study aimed to compare the etiologic spectrum of diseases causing fever of unknown origin (FUO) and methods for definitive diagnosis in a tertiary care hospital in the Republic of North Macedonia during two different time periods.

Patients and methods. There were analysed retrospectively the causes for FUO and final diagnostic approaches in 185 patients with classic FUO that were treated at the University Hospital for Infectious Diseases in Skopje during two time periods. Seventy nine patients were treated during 1991 to 1995 and 106 patients during 2011 to 2015.

Results. When comparing these two periods, infections were present in 46.8% and 29.2% (p = 0.014), non-infective inflammatory disorders in 22.8% and 25.5% (p = 0.674), neoplasms in 10.1% and 13.2% (p = 0.522), miscellaneous in 8.9% and 12.3% (p = 0.461) and undiagnosed cases in 11.4% and 19.8% (p = 0.124), respectively. The most common causes for FUO during the first period were abscesses (8.9%), tuberculosis and systemic lupus erythematosus (7.6% each), whereas in the second period the commonest causes were adult onset Still disease and solid organ neoplasm (7.6% each), polymyalgia rheumatica, abscesses and visceral leishmaniasis (5.7% each). The newer imaging techniques and clinical course evaluation had superior diagnostic significance during the second period.

Conclusion. A changing pattern of diseases causing FUO during the examined periods was evident. Infections continue to be the most common cause but with decreasing incidence when compared to 20 years ago. Even nowadays clinical evaluation and follow-up still remain the vital diagnostic tools in determining the etiology of FUO.

Introduction. More than 50% of glomerular crescent formation is required for a diagnosis of crescentic glomerulonephritis in a kidney biopsy. Although treatment protocols have been established for diffuse crescentic glomerulonephritis, there is no standard treatment for patients with fewer crescents in renal biopsies. In this study the importance of crescent percentage and clinical features on renal survival independent of underlying disease was investigated.

Methods. This retrospective observational study was conducted between 2013 and 2017. Forty-nine patients with crescent formation in their kidney biopsies were evaluated. We compared clinicopathological features and renal survival. We evaluated the factors affecting the course of end stage renal disease (ESRD).

Results. A total of 49 patients (57% male and median age 49 years) were enrolled in this study. 39% of patients developed ESRD at follow-up. Logistic regression analysis showed that the requirement for renal replacement treatment on admission (p < 0.001), serum creatinine level above 2.7 mg/dL (p < 0.001), the presence of more than 50% glomerulosclerosis (p = 0.04) and more than 34% crescent formation (p = 0.002) were significantly associated with ESRD. Kaplan-Meier survival analysis revealed that patients with less than 34% crescent in kidney biopsy and a serum creatinine level less than 2.7 mg/dL had increased kidney survival (log-rank test p: 0.01 and p: 0.002).

Conclusion. Patients with crescent formation in kidney biopsy more than 34% should be evaluated for more aggressive treatment modalities regardless of the underlying disease, especially if the serum creatinine level is above 2.7 mg/dL.

Hypokalemic periodic paralysis (HOKPP) is a rare neuromuscular disorder caused by altered transport of cellular potassium that leads to significant muscle weakness of the extremities. Paralytic attacks are induced by a drop in the serum potassium level and they have been associated with specific triggers. This case describes a 21-year-old male who has had recurrent presentations of acute paralytic attacks following vigorous physical activity. At presentation, this patient exhibited flaccid paralysis of all skeletal muscles below the neck, but was alert and oriented with stable vital signs. The patient was found to have a potassium level of 2.1 mmol/L and an EKG demonstrating U waves (characteristic of hypokalemia). The patient was treated with potassium supplementation with resolution of symptoms. The mainstay of prevention of long term permanent muscle weakness is avoidance of triggers that can lead to hypokalemia. Through education on disease process and lifestyle modifications, we were able to end the cycle of recurrent hospital readmissions and the subsequent financial burden this generated for the patient and his family.

Background. Deposition of calcium pyrophosphate crystals in the cervical spine around the odontoid process may lead to neck pain and fever. This condition is called crowned dens syndrome (CDS).

Case report. An 89-year-old female presented with complaints of fever for one-month duration and recent onset neck pain. During her admission, she developed right knee pain with evidence of chondrocalcinosis on X-ray. Considering her clinical presentation in setting of pseudogout, she had a CT scan of her neck that revealed erosion of the dens and hyperdense soft tissue surrounding the odontoid process. Based on her clinical and radiologic presentation, she was diagnosed with crowned dens syndrome and started on NSAIDs. Unfortunately, she did not respond to NSAIDs and was switched to Colchicine, which resulted in immediate improvement in her symptoms.

Conclusions. We present this case to stress the importance of keeping crowned dens syndrome as one of the differentials in an elderly patient presenting with fever and neck pain.