With the incorporation of targeted therapies in routine cancer therapy, it is imperative that the array of toxicities associated with these agents be well-recognized and managed, especially since these toxicities are distinct from those seen with conventional cytotoxic agents. This review will focus on these renal toxicities from commonly used targeted agents. This review discusses the mechanisms of these side effects and management strategies. Anti-vascular endothelial growth factor (VEGF) agents including the monoclonal antibody bevacizumab, aflibercept (VEGF trap), and anti-VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKIs) all cause hypertension, whereas some of them result in proteinuria. Monoclonal antibodies against the human epidermal growth factor receptor (HER) family of receptors, such as cetuximab and panitumumab, cause electrolyte imbalances including hypomagnesemia and hypokalemia due to the direct nephrotoxic effect of the drug on renal tubules. Cetuximab may also result in renal tubular acidosis. The TKIs, imatinib and dasatinib, can result in acute or chronic renal failure. Rituximab, an anti-CD20 monoclonal antibody, can cause acute renal failure following initiation of therapy because of the onset of acute tumor lysis syndrome. Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, can result in proteinuria. Discerning the renal adverse effects resulting from these agents is essential for safe treatment strategies, particularly in those with pre-existing renal disease.
Solid organ transplant recipients are at increased risk for infections due to chronic immunosuppression. Diarrhea is a commonly encountered problem post transplantation, with infectious causes of diarrhea being a frequent complication. Viral infections/enteritides in solid organ transplant recipients often result from frequently encountered pathogens in this population such as cytomegalovirus, adenovirus, and norovirus. However, several emerging viral pathogens are increasingly being recognized as more sensitive diagnostic techniques become available. Treatment is often limited to supportive care and reduction in immunosuppression, though antiviral therapies mayplay a role in the treatment in certain diseases. Viral enteritis is an important entity that contributes to morbidity and mortality in transplant recipients.
West Nile virus (WNv) is a major cause of viral encephalitis in the United States. WNv infection is usually asymptomatic or a limited febrile illness in the immunocompetent hosts, although a small percentage can develop neuroinvasive disease. Neuroinvasive disease due to WNv in solid organ transplant recipients occurs at higher rates than observed in the general population and can have long term neurological sequalae. Methods We retrospectively reviewed medical records of all solid organ transplant recipients at our institution who tested positive for WNv from 2010 to 2018. Two reviewers performed electronic searches of Medline, Embase, Cochrane Library of literature of WNv infections in SOT. Descriptive statistics were performed on key variables. Results Eight recipients (mean age 54, five males) were diagnosed with neuroinvasive WNv infection at our institution. Distribution of infection was as follows: five kidney transplants, one in each kidney‐pancreas, liver, and lung. Diagnoses included meningitis (3), encephalitis (1), meningo‐encephalitis (4). Median time from transplant to infection was 49.8 months (2.7–175.4). No infections were considered donor‐derived. Five patients received treatment with IVIG. Six patients were alive at median follow‐up of 49.5 months (21.7–116.8). We identified 29 studies published from 2002 to 2019. Median time from transplant to infection was 14.2 months, with similar allograft distribution; 53% were donor‐derived infections. Conclusion WNv infections in solid organ transplant recipients can be a consequence of organ donation or can be acquired via the community. Infections can be more severe in SOT recipients and lead to neuroinvasive disease.
Objective: To assess the severity of ulcerative colitis on first colonoscopic examination. Study Design: Prospective cross-sectional (correlational) study design. Place and Duration of Study: Study was conducted in Gastroenterology Outpatient Department of Pak Emirates Military Hospital, Rawalpindi, from Nov 2017 to Oct 2018. Methodology: An aggregate of 200 patients within the age range of 12-70 years, were included in the studythrough non-probability consecutive sampling. The data was collected by the self-administered questionnaireincluding age, gender, stool frequency, P/R bleed, systemic features of ulcerative colitis & colonoscopic findings.Effectiveness of the procedures was noted on a pre-designed performa and the endoscopic assessment was based upon mayo score severity of colitis graded from Normal (0) to Severe (3). Data was analyzed by using SPSS-19. Results: The mean age of the participants was reported 38 ± 2.1 years. Out of 200 participants 104 (52%) weremale, diarrhea with PR bleed was positive in 180 (90%) & anemia in 154 (77%). Colonoscopic findings showedthat 72 (36%) were with Left sided colitis (Montreal Class E2) & 82 (41%) with proctitis (Montreal class E1). Severe disease (Mayo endoscopic Score 3) was positive in 118 (59%) patients. Conclusion: Assessment of severity of UC is important as it determines the long term management & alsovaluable for risk stratification to predict the prognosis. Our findings feature the requirement for system levelenhancements to encourage the proper delivery of colonoscopy services dependent on individual risk. Keywords: , , , .
Objective: To look for frequency and associated socio-demographic factors of newly diagnosed patients of heaptocellular carcinoma (HCC) among patients treated adequately for hepatitis C infection. Study Design: Correlational study. Place and Duration of Study: Gastroenterology Department, Pak Emirates Military Hospital Rawalpindi, fromNov 2017 to Oct 2018. Methodology: This analysis was performed on 170 patients treated effectively for hepatitis C with standard antiviral therapy at our hospital. They were followed up for two years after the sustained viral response has been achieved. Ultrasonography was done in all cases and contrast enhanced computerized tomography scan done on patients who were positive on ultrasound. Factors like age, gender, genotype of heaptocellular carcinoma, presence of cirrhosis and model for end-stage liver disease (MELD) score were related with presence of heaptocellular carcinoma among the target population. Results: Out of 170 patients included in final analysis 121 were male, 49 were female. About 53 patients werediagnosed as suffering from heaptocellular carcinoma while 117 were negative for that. Thirty six patients hadcirrhosis while 134 non cirrhotic. After applying the binary logistic regression genotypes other than 3, high model for end-stage liver disease score & presence of cirrhosis had a strong relationship with presence of heaptocellular carcinoma among the patients treated for hepatitis C virus. Conclusion: Physicians and patients cannot ignore the possibility of a malignant outcome even after successfultreatment of hepatitis C. Local protocols should be set for screening especially the high risk cases even aftertreatment of hepatitis..........
In this paper, we fabricated semi-interpenetrating polymeric network (semi-IPN) of hydroxypropyl-β-cyclodextrin-grafted-poly(acrylic acid)/poly(vinyl pyrrolidone) (HP-β-CD-g-poly(AA)/PVP) by the free radical polymerization technique, intended for colon specific release of dexamethasone sodium phosphate (DSP). Different proportions of polyvinyl pyrrolidone (PVP), acrylic acid (AA), and hydroxypropyl-beta-cyclodextrin (HP-β-CD) were reacted along with ammonium persulphate (APS) as initiator and methylene-bis-acrylamide (MBA) as crosslinker to develop a hydrogel system with optimum swelling at distal intestinal pH. Initially, all formulations were screened for swelling behavior and AP-8 was chosen as optimum formulation. This formulation was capable of releasing a small amount of drug at acidic pH (1.2), while a maximum amount of drug was released at colonic pH (7.4) by the non-Fickian diffusion mechanism. Fourier transformed infrared spectroscopy (FTIR) revealed successful grafting of components and development of semi-IPN structure without any interaction with DSP. Thermogravimetric analysis (TGA) confirmed the thermal stability of developed semi-IPN. X-ray diffraction (XRD) revealed reduction in crystallinity of DSP upon loading in the hydrogel. The scanning electron microscopic (SEM) images revealed a rough and porous hydrogel surface. The toxicological evaluation of semi-IPN hydrogels confirmed their bio-safety and hemocompatibility. Therefore, the prepared hydrogels were pH sensitive, biocompatible, showed good swelling, mechanical properties, and were efficient in releasing the drug in the colonic environment. Therefore, AP-8 can be deemed as a potential carrier for targeted delivery of DSP to treat inflammatory bowel diseases.
Background: Beta-lactam allergies (BLAs) are common in hospitalized patients, including transplant recipients. BLA is associated with decreased use of preferred surgical site infection (SSI) prophylaxis and increased SSIs, but this has not been studied in the transplant population. Methods:We reviewed adult heart, kidney, and liver transplant recipients between January 1, 2016 and December 31, 2019 to characterize reported BLA and collect SSI prophylaxis regimens at time of transplant. We compared the use of preferred SSI prophylaxis and SSI incidence based on reported BLA status. Post hoc we collected antibiotic days of therapy (DOT) (excluding pneumocystis prophylaxis) in the 30-day period posttransplant for patients without SSI. We utilized descriptive statistics for comparisons. Results:Of 691 patients included (116 heart, 400 kidney, and 175 liver transplant recipients), 118 (17%) reported BLA. Rash and hives were the two most reported BLA reactions (36% and 24%), categorized as potential T-cell mediated and IgE mediated, respectively. Preferred SSI prophylaxis was prescribed in 13 (11%) patients with BLA and 573 (92%) without BLA (p < .001). No difference could be detected in SSI incidence between BLA and non-BLA patients (4.2 vs. 4.3%, p = 1.0). Of 659 without SSI, 169 (25.6%) received antibiotics within 30 days of transplant; mean antibiotic DOT for BLA and non-BLA patients were 3.5 ± 8.0 versus 2.3 ± 5.8, p = .12. Conclusion:BLA transplant recipients received nonpreferred SSI prophylaxis more frequently than non-BLA recipients, but there was no difference in 30-day SSIs between the groups. One-fourth of solid organ transplant recipients received systemic antibiotics within 30 days of transplant.
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