Combination drug regimens for metastatic clear cell renal cell carcinoma

Renal cell carcinomas (RCC) make up about 90% of kidney cancers, of which 80% are of the clear cell subtype. About 20% of patients are already metastatic at the time of diagnosis. Initial treatment is often cytoreductive nephrectomy, but systemic therapy is required for advanced RCC. Single agent targeted therapies are moderately toxic and only somewhat effective, leading to development of immunotherapies and combination therapies. This review identifies limitations of monotherapies for metastatic renal cell carcinoma, discusses recent advances in combination therapies, and highlights therapeutic options under development. The goal behind combining various modalities of systemic therapy is to potentiate a synergistic antitumor effect. However, combining targeted therapies may cause increased toxicity. The initial attempts to create therapeutic combinations based on inhibition of the vascular endothelial growth factor or mammalian target of rapamycin pathways were largely unsuccessful in achieving a profile of increased synergy without increased toxicity. To date, five combination therapies have been approved by the U.S. Food and Drug Administration, with the most recently approved therapies being a combination of checkpoint inhibition plus targeted therapy. Several other combination therapies are under development, including some in the phase 3 stage. The new wave of combination therapies for metastatic RCC has the potential to increase response rates and improve survival outcomes while maintaining tolerable side effect profiles.     

Replicating Viral Vector-Based Vaccines for COVID-19: Potential Avenue in Vaccination Arena

The “severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)” is the third member of human coronavirus (CoV) that is held accountable for the current “coronavirus disease 2019 (COVID-19)” pandemic. In the past two decades, the world has witnessed the emergence of two other similar CoVs, namely SARS-CoV in 2002 and MERS-CoV in 2013. The extent of spread of these earlier versions was relatively low in comparison to SARS-CoV-2. Despite having numerous reports inclined towards the zoonotic origin of the virus, one cannot simply sideline the fact that no animal originated CoV is thus far identified that is considered similar to the initial edition of SARS-CoV-2; however, under-sampling of the diverse variety of coronaviruses remains a concern. Vaccines are proved to be an effective tool for bringing the end to such a devastating pandemic. Many vaccine platforms are explored for the same but in this review paper, we will discuss the potential of replicating viral vectors as vaccine carriers for SARS-CoV-2.     

Perspectives of nuclear diagnostic imaging in diabetic cardiomyopathy

Diabetic cardiomyopathy is a ventricular dysfunction in the absence of coronary artery disease, valvular or hypertensive heart disease. The mechanisms underlying diabetic cardiomyopathy may involve metabolic disturbances, myocardial fibrosis, small vessel disease, microcirculation abnormalities, cardiac autonomic neuropathy and insulin resistance.Diagnostic problems emerge because no specific disease pattern characterizes the disease and because there may be coexistence in diabetes of coronary artery disease and hypertension as independent but compounding causes of biochemical, anatomical and functional alterations impairing cardiac function.In this paper we will review the role of nuclear imaging today, concentrating on the diagnostic capabilities of radionuclide ventriculography, to study the effect of insulin resistance and, more extensively, gated-single photon emission computed tomography with Tc-99m labelled agents.A broad analysis will be dedicated to: 1) positron emission tomography using perfusion agents, with the potential to quantify resting and stress blood flow and coronary flow reserve; 2) radionuclide procedures evaluating aerobic and anaerobic cardiac metabolism; and 3) cardiac neurotransmission imaging, studying the autonomic neuropathy.     

Metabolic alkalosis due to the use of an oligoantigenic diet in infancy

A 7-month-old boy on an oligoantigenic diet because of multiple food intolerances presented with anorexia, failure to gain weight and severe hypochloremic metabolic alkalosis with hyperreninemia. Clinical symptoms and biochemical abnormalities disappeared after adequate dietary supplementation with potassium and sodium chloride. This case emphasizes that minimal daily mineral requirements must be provided in infant diets, and highlights the risk of nutritional deficiencies inherent in the prolonged use of oligoantigenic diets not adequately supplemented.     

Comparison of the main oesophageal pathophysiological characteristics between short- and long-segment Barrett's oesophagus

AIM: To assess the oesophageal manometric characteristics and 24-h pH profiles of patients with both short-segment and long-segment Barrett's oesophagus and compare them with those of patients with reflux oesophagitis and controls. METHODS: Seventy-nine patients who had undergone upper digestive endoscopy were recruited: 16 had short-segment Barrett's oesophagus, 13 had long-segment Barrett's oesophagus, 25 had grade III oesophagitis according to the Savary-Miller classification and 25 were used as controls. The diagnosis of Barrett's oesophagus was based on the histological detection of specialized intestinal metaplasia, which extended < 3 cm into the oesophagus in patients with short-segment disease and > 3 cm in patients with long-segment disease. All subjects underwent oesophageal manometry and basal 24-h oesophageal pH monitoring. RESULTS: The lower oesophageal sphincter pressure was significantly lower in patients with reflux oesophagitis and short-segment and long-segment Barrett's oesophagus than in controls (P=0.0004-0.0001), but there was no difference among the three reflux groups. The peristaltic wave amplitude of patients with long-segment Barrett's oesophagus was significantly lower than that of controls (P=0.002) and patients with short-segment Barrett's oesophagus (P=0.02), but was no different from that of patients with reflux oesophagitis. The percentage of non-propagated wet swallows was significantly higher in patients with reflux oesophagitis and short-segment and long-segment Barrett's oesophagus when compared with that of controls (P=0.0004-0.0001). The total percentage of time the oesophagus was exposed to pH < 4.0 was significantly higher in patients with reflux oesophagitis and short-segment and long-segment Barrett's oesophagus (P=0.0001) than in controls, and was higher in patients with long-segment disease than in those with short-segment disease (P=0.01). CONCLUSIONS: Long-segment Barrett's oesophagus is characterized by a greater impairment of peristaltic wave amplitude and a higher oesophageal acid exposure than is short-segment Barrett's oesophagus. However, both forms are linked to increased acid reflux.     

Eradication of Helicobacter pylori may reduce disease severity in rheumatoid arthritis

BACKGROUND: A triggering infectious agent has long been postulated in rheumatoid arthritis. Data on the possible role of Helicobacter pylori infection are lacking. AIM: To assess the effect of H. pylori eradication in patients with rheumatoid arthritis. METHODS: Fifty-eight adult patients with established rheumatoid arthritis and dyspeptic symptoms were recruited - 28 were H. pylori-positive and 30 were H. pylori-negative on the basis of invasive tests. All infected patients were treated successfully. We evaluated the disease activity using clinical and laboratory parameters at baseline and every 4 months during 2 years, and compared the variations in the two subgroups. RESULTS: H. pylori-eradicated rheumatoid arthritis patients showed progressive improvement over time (P < 0.0001) of all clinical indices compared with baseline, whereas H. pylori-negative rheumatoid arthritis patients remained substantially unchanged. After 2 years, H. pylori-eradicated rheumatoid arthritis patients differed significantly (P < 0.04-0.0001) from patients without H. pylori infection in terms of improvement of all clinical parameters. At the same time point, several laboratory indices (erythrocyte sedimentation rate, fibrinogen, alpha2-globulins and antinuclear antibody) showed significantly lower values (P < 0.02-0.0003) in the H. pylori-eradicated subgroup compared to the H. pylori-negative subgroup. CONCLUSIONS: Our data suggest that H. pylori infection is implicated in the pathogenesis of rheumatoid arthritis, in that its eradication may induce a significant improvement of disease activity over 24 months. H. pylori eradication seems to be advantageous in infected rheumatoid arthritis patients, but controlled studies are needed.     

Sublingual allergen-specific immunotherapy in allergic rhinitis and related pathologies: Efficacy in a paediatric population

The aim of this study was to demonstrate the efficacy and safety of the sublingual-swallow allergen-specific immunotherapy (SLIT) in a paediatric population suffering from allergic rhinitis and related pathologies. From March 1994 through March 2000, at our ENT Department 4000 children (1800 male and 2200 female), aged 3 to14 years, were examined for recurrent nasal obstruction and nasal polyps. 2400 (60%) of them were allergic and underwent the following investigations: Impedance test, Pure tone audiometry, rhinomanometry, Prick test, RAST, nasal provocation test and paranasal sinus TC without contrast media. Of the allergic group we admitted 288 patients(12%) to a 3 yr SLIT, meeting the following criteria: children aged 5 years or more, mono-sensitised to one allergen and with family cooperation support. After three years of SLIT, we observed complete symptom remission and a marked improvement in instrumental examinations in 80% of these children. The improvement was poor in 8% of patients, while in 12% of the subjects no changes in symptoms and instrumental results were detected. These results are in agreement with previously published studies and confirm that SLIT can be a valid tool for treating allergic upper respiratory tract diseases in children.