Unravelling a Triad: A Rare Case of Takayasu Arteritis, Hashimoto's Thyroiditis, and Psoriasis in a Young Female With Heart Failure.

Takayasu arteritis (TA) is an autoimmune entity of unknown aetiology causing granulomatous thickening of large and medium-sized arteries. Common symptoms include claudication, headaches, dizziness, syncope, visual changes, and palpitations. Diverse cardiac manifestations, such as ischemic heart disease, significant aortic regurgitation, and pulmonary hypertension, are associated with TA, although they rarely manifest as congestive heart failure. Radio-imaging, including CT angiography and MR angiography, along with more invasive procedures such as conventional angiography, are often used for diagnosis. Treatment is done with corticosteroids, steroid-sparing agents, biologics, and revascularization procedures. Here, we have a case of a 17-year-old Indian female who presented to us with a complaint of abdominal pain. She was diagnosed with Hashimoto's thyroiditis a few years ago, along with a history of congestive heart failure. On general examination, blood pressure was asymmetrical in the upper limbs with the presence of bilateral carotid bruit. There was also the presence of extensive scaly lesions on the extensor surface of all four limbs, suggestive of psoriasis. Radio-imaging confirmed the diagnosis of TA. CT angiography also showed total occlusion of the celiac trunk and proximal left gastric artery, which was likely the cause of her symptoms. The patient received treatment with corticosteroids in conjunction with methotrexate, along with other supportive drugs. TA with congestive heart failure has been occasionally described in the literature, while the association of TA with psoriasis is much rarer. The simultaneous occurrence of various autoimmune diseases is common, but the triad of Hashimoto thyroiditis, psoriasis, and TA with an initial presentation of heart failure is unique. Due to the common co-occurrence of autoimmune conditions, early and thorough patient evaluation with comprehensive studies is imperative for optimal health outcomes.

Idiopathic Retroperitoneal Fibrosis Presented As Urinary Tract Obstruction.

Retroperitoneal fibrosis (RPF) or Ormond's disease is a very uncommon fibro-inflammatory disease, under the umbrella of systemic autoimmune diseases. The majority of cases are idiopathic, known as idiopathic RPF (IRPF); however, diseases secondary to other causes are also seen in clinical practice. The commonest presenting features are seen due to the effects of fibrous tissue around iliac vessels, aorta and ureters, where compression of ureters is the major and most common complication. Computed tomography (CT) scans and magnetic resonance imaging (MRI) are the modalities of choice for the diagnosis. The primary management involves medical therapy with corticosteroids and reserving surgical options for ureteric obstruction and related complications. We present a case of a 65-year-old man who presented with bilateral pedal oedema, facial puffiness, decreased appetite, decreased urine output, and breathlessness with dry cough, tachypnoea, hypoxia and crepitation in both lung fields on examination. The blood investigations were suggestive of acute kidney injury (AKI); whereas radio imaging diagnosed him as a case of bilateral hydroureteronephrosis with RPF. The patient was treated for AKI in the case of IRPF. Once the patient stabilized, a low-dose systemic steroid was started for IRPF, and subsequently, the patient underwent stent placement surgery for ureteric obstruction. RPF, being a rare disease, is difficult to diagnose. However, CT and MRI scanning can easily reveal fibrous tissue surrounding the aorta and ureters. Medical management with glucocorticoids is the backbone drug for the disease, keeping surgery as a reserved option for ureteric obstruction and its complications.

Emphysematous Cystitis: A Fatal Complication of Uncontrolled Type-2 Diabetes Mellitus.

Emphysematous cystitis (EC) is a rare type of complicated urinary tract infection mostly seen in elderly females with diabetes, characterized by gas within the bladder lumen and wall. The presenting symptoms are variable, ranging from no symptoms to severe sepsis. The commonly isolated organisms in urine cultures are Escherichia coli and Klebsiella pneumoniae. Imaging studies, namely plain conventional abdominal radiography and computed tomography, are necessary to make a definitive diagnosis of EC. The management includes medical treatment with culture-guided antibiotics, whereas surgical intervention such as cystectomy is rarely required in severe cases. Here, we have a case of a 48-year-old diabetic female diagnosed with EC on radio imaging. The patient was aggressively treated with higher antibiotics such as piperacillin/tazobactam, clindamycin, and fosfomycin along with measures to control blood sugars. However, she developed severe sepsis and succumbed to death. Our report presents one of the rare cases of EC as a life-threatening complication in diabetics, suggesting that every case of urinary tract infection in uncontrolled diabetics should be thoroughly investigated and treated to prevent fatal complications.

A Rare Phenotype of Inherited Cerebellar Ataxia.

Ataxia is a syndrome of imbalance and incoordination, categorized as hereditary ataxias, degenerative ataxias (non-hereditary), and acquired ataxias. Hereditary ataxia is further classified based on its mode of inheritance. Here, we have reported a case of early-onset autosomal recessive cerebellar ataxia with retained reflexes in a young male with positive family history. A young male presented with ten years history of tremors in both hands and head, aggravated with work and relieved with rest, and imbalance while walking, which has now progressed to the level where the patient cannot walk without support. The patient's younger brother also had a similar history. Central nervous system examination revealed cerebellar ataxia with retained reflexes. After ruling out other causes of ataxia in this age group by investigations, we could make the diagnosis of early-onset cerebellar ataxia with retained tendon reflexes (autosomal recessive). Presenting as a disease of variable presentation, the important diagnostic cues are classification and localization of ataxia. The investigations should be focusing on those cases of ataxias that are treatable. Family history is important to identify hereditary ataxias, as well as in genetic counselling of the affected patients.

Mucormycosis, Diabetes and COVID-19 Pneumonia: Unleashing the Facts.

Background Mucormycosis (MM) is an angioinvasive locally destructive fungal infection. Before the coronavirus disease 2019 (COVID-19) pandemic, it was associated with diabetes (particularly diabetic ketoacidosis), immunosuppressive drugs and trauma. Among its various forms, cerebral invasion is considered to be highly fatal even if with long-term treatment. Treatment with injection amphotericin B (Amph-B) with early surgical interventions is highly efficacious. Liposomal preparation is considered to be superior in the context of fewer side effects. Methods We present a single-centre prospective study of 124 patients with MM in a tertiary care hospital. After the approval from the ethics committee, basic information was taken from all patients including all available past history about the COVID-19 infection and treatment. The studied outcomes were discharge, death and number of days of hospitalisation. Secondary objectives were to estimate the association of MM with known risk factors, to find the association of an outcome with various inflammatory markers, to determine adverse events with the use of injection Amph-B and posaconazole and to find the case fatality rate of MM. Results In our study, we observed that the number of patients with MM was double in the less than 60 years age group. However, mortality was 33.3% in the elderly as compared to 15.29% in patients less than 60 years of age. The majority of the patients (69.35%) were males, but no significant difference in mortality was seen between males and females. The case fatality rate was 20.97%. Ocular symptoms such as orbital swelling and pain were the common presenting symptoms. Almost all patients (93.54%) were diabetics. The non-diabetic group consisted of only 8 (6.4%) patients, and therefore, the comparison was not possible. A total of 20 (16%) out of 124 patients who had received high-dose steroids showed higher mortality (55%). Maximum patients (65.32%) had presented with MM following a past COVID-19 infection. However, a significant number of MM patients (20.96%) had a recent COVID infection and had higher mortality (57.69%) compared to their counterparts. The most common site of involvement in our study was the paranasal sinus (50%) and the outcome was the best in those patients whose disease was localised only to the sinuses, although among 14 (11.29%) patients with cerebral involvement, mortality was maximum (42.85%). Renal impairment and dyselectrolytemia were the most common adverse effects of Amph-B, and 46.42% of patients required surgical removal of the local part. Conclusion We saw that diabetes was a major contributory factor in the etiopathogenesis of MM. COVID-19 could also be a major causative factor by impairing the immune system; however, further studies at the molecular level are required to establish an association. The use of steroid cannot be the only independent risk factor, and other associated factors must be present. Treatment with antifungal and early surgical intervention had good outcomes. Treatment with conventional lyophilized Amph-B was equally efficacious as lipid-based solutions, but with more side effects. Hypokalemia and hypocalcemia were the most common electrolyte abnormalities associated with the use of injection Amph-B. Uncontrolled diabetes, the severity of the COVID-19 infection at presentation, acidosis, a high C-reactive protein level (above 100) and local brain involvement were associated with a poor outcome.

Targeting vascular endothelial growth factor in renal cell carcinoma.

Renal cancer is the most lethal of all urological malignancies with overall 5-year survival rates of around 60%. The predominant reason for the poor prognosis of this cancer has been the relative lack of effective systemic therapy for advanced metastatic disease. Until recently immunotherapy with interleukin-2 or interferon-alpha has been the standard of care for metastatic renal cell carcinoma (RCC); however, the response rates for these treatments were at best only 3-21%. The use of molecular biological techniques has led to a greater understanding of the genetic basis of RCC. Mutations of the von Hippel-Lindau (VHL) gene on chromosome 3p25 with the resultant overexpression of hypoxia-inducible factors (HIFs) have been shown to lead to the development of clear-cell RCC. The unearthing of the pathways downstream of VHL has led to the development of numerous novel therapies that specifically target HIF-related genes such as vascular endothelial growth factor (VEGF). In this article, we explore the VHL-HIF-VEGF pathway that plays a fundamental role in the development of renal cancer. In addition, we review the evidence base for the use of these new targeted therapies for advanced RCC and uniquely include the latest practice guidelines from the European Association of Urology, the United States National Comprehensive Cancer Network and the National Institute for Health and Clinical Excellence.

Dermoid cyst of the spermatic cord: a rare cause of benign inguinal lump.

Dermoid cyst of the spermatic cord is an extremely rare pathology seen at the urological clinic. We present the case of a 26-year-old man who presented with a groin lump, thought to be a lipoma or a hydrocoele of the cord. The final histopathological analysis established the diagnosis of a dermoid cyst.

Up-regulation of endothelial delta-like 4 expression correlates with vessel maturation in bladder cancer.

PURPOSE: Angiogenesis and vascular endothelial growth factor (VEGF) expression are associated with a poor outcome in bladder cancer. To understand more about the mechanisms, we studied the role of delta-like 4 (DLL4), an endothelial-specific ligand of the Notch signaling pathway, in bladder cancer angiogenesis. EXPERIMENTAL DESIGN: The expression of DLL4, CD34, and VEGF were studied in a cohort of 60 bladder tumors and 10 normal samples using quantitative PCR. In situ hybridization was used to study the pattern of DLL4 expression in 22 tumor and 9 normal samples. Serial sections were also stained for CD34 and alpha-smooth muscle actin (alpha-SMA) using conventional immunohistochemistry. RESULTS: The expression of DLL4 was significantly up-regulated in superficial (P < 0.01) and invasive (P < 0.05) bladder cancers. DLL4 expression significantly correlated with CD34 (P < 0.001) and VEGF (P < 0.001) expression. The in situ hybridization studies showed that DLL4 was highly expressed within bladder tumor vasculature. Additionally, DLL4 expression significantly correlated with vessel maturation as judged by periendothelial cell expression of alpha-SMA, 98.7% of DLL4-positive tumor vessels coexpressed alpha-SMA, compared with 64.5% of DLL4-negative tumor vessels (P < 0.001). High DLL4 expression may have prognostic value in superficial and invasive bladder. CONCLUSION: DLL4 expression is associated with vascular differentiation in bladder cancer; thus, targeting DLL4 may be a novel antiangiogenic therapy.

Up-regulation of delta-like 4 ligand in human tumor vasculature and the role of basal expression in endothelial cell function.

The Notch signaling pathway and the delta-like 4 ligand (DLL4) play key roles in embryonic vascular development. Many of the pathways involved in embryonic vascular development also play important roles in tumor angiogenesis. In this study, we assessed the expression of DLL4 in primary renal cancer and investigated the biological function of DLL4 in primary endothelial cells. Using real-time quantitative PCR and in situ hybridization, we showed that the expression of DLL4 was up-regulated within the vasculature of clear cell-renal cell carcinoma almost 9-fold more than normal kidney and was correlated with the expression of vascular endothelial growth factor (VEGF). The expression of DLL4 in endothelial cells was up-regulated by VEGF and basic fibroblast growth factor synergistically, and by hypoxia through hypoxia-inducible factor 1alpha. Down-regulation of DLL4 expression with RNA interference led to decreased expression of HEY1 and EphrinB2, and the inhibition of endothelial cell proliferation, migration, and network formation, all of which are important processes in tumor angiogenesis. The inhibition of proliferation occurred via the induction of cell cycle arrest in G0-G1 by increased expression of p21 and decreased phosphorylation of retinoblastoma. We conclude that an optimal window of the DLL4 expression is essential for tumor angiogenesis and that selective modulation of the DLL4 expression within human tumors may represent a potential novel antiangiogenic therapy.