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A rare case of Diffuse Alveolar Hemorrhage (DAH) due to Warfarin Toxicity

Abstract

Introduction: Warfarin is one of the most frequently used anticoagulant agents in the clinic. The most important adverse effect of warfarin is hemorrhage of vital organs, such as lung and brain. Diffuse Alveolar Hemorrhage (DAH) is a rare clinical condition which occurs due to variety of medical disorders. Although it’s rarely reported, DAH can be a result of coagulopathy prompted by warfarin therapy. In this study we present a case of DAH, caused by warfarin toxicity which referred to the hospital with non-specific respiratory symptoms.

Case Presentation: A 41-year-old female patient referred to the hospital complaining of shortness of breath, cough and dizziness. She had been taking warfarin due to mitral valve replacement for the past 10 years. Her recent symptoms began shortly after taking amoxicillin, a few days before admission. Early clinical examination and paraclinical studies reveal DAH as the cause of respiratory symptoms. The patient was then intubated and received Fresh Frozen Plasma, Packed Cells and oral vitamin K. Laboratory findings apart from increased INR, PT, ESR and CRP were all within normal range. After the initiation of treatment patient’s INR decreased and her clinical condition improved. Follow-up CT-Scan and bronchoscopy also confirmed resolving DAH.

Conclusions: The usage of warfarin in anticoagulation should be closely monitored due to its narrow therapeutic window and other factors, including its interaction with other medications such as antibiotics. Warfarin toxicity can lead to DAH, a life-threatening condition which can be presented with non-specific symptoms and deteriorate patient’s clinical condition in a short time. Therefore, it is of utmost importance to watch closely for primary symptoms of such rare incident in patients under warfarin therapy and initiate treatment as soon as possible, to prevent mortality.

Open access
Immunosuppressive treatment for peripheral neuropathies in Sjogren’s syndrome – a systematic review

Abstract

Background: Sjogren’s syndrome (SS) is among the most frequent autoimmune diseases and one of its most severe extraglandular manifestations is peripheral neuropathy. There is no consensus about peripheral neuropathy treatment in SS. Our aim is to identify studies proving the efficiency of immunosuppressive treatment on peripheral neuropathies in SS.

Methods: The search was conducted on the PubMed (MEDLINE) database. Studies with patients diagnosed with SS and peripheral neuropathy were included. Treatment with one of the following was among inclusion criteria: glucocorticoids (GC), rituximab (RTX), azathioprine (AZA), mycophenolic acid (MMF), cyclophosphamide (CP), methotrexate (MTX), plasmapheresis or iv immunoglobulins (IV IG).

Results: A total of 116 results were found and abstracts were examined. 103 papers were excluded, and the remaining 13 papers were analyzed. They were 3 case series and 10 case reports, retrospective, totalizing 62 patients of which 22 (35,5%) received IV IG, 8 (13%) received RTX, 7 (11%) CP, and 5 (8%) received only GC. Drug associations containing corticosteroids were frequent. Of those 22 treated with IV IG, 18 patients improved (82%), and 4 stabilized (18%).

IV IG was useful in sensory, motor and sensorimotor neuropathies. CP had good results in mononeuritis multiplex, while autonomic neuropathies responded well to GC or RTX. AZA, RTX, MTX, MMF or plasmapheresis were not used alone. Follow-up periods were heterogenous and the evaluation of the neuropathy was not systematic.

Conclusion: There is only low level evidence (retrospective case reports and case series). In most cases, IV IG treatment in patients with peripheral neuropathies and SS resulted in clinical improvement, while other therapies, such as RTX, corticosteroids and CP proved to be useful in a handful of cases.

Open access
The changing pattern of fever of unknown origin in the Republic of North Macedonia

Abstract

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.

Open access
Crowned dens syndrome presenting as pyrexia of unknown origin (PUO)

Abstract

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.

Open access
Hypokalemic periodic paralysis – the importance of patient education

Abstract

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.

Open access
Liraglutide exerts an anti-inflammatory action in obese patients with type 2 diabetes

Abstract

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.

Open access
Medical evaluation and management of male and female voiding dysfunction: a review

Abstract

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.

Open access
Non-alcoholic fatty pancreas disease – practices for clinicians

Abstract

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.

Open access
Prognostic factors in glomerular diseases with crescents

Abstract

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.

Open access