Psychosocial Barriers and Their Impact on Hepatocellular Carcinoma Care in US Veterans: Tumor Board Model of Care.

Background: Psychosocial barriers, including low socioeconomic status, homelessness, alcohol and substance use disorders, and psychiatric disorders are prevalent in US veterans. Our study aims to identify the prevalence of psychosocial barriers in veterans diagnosed with hepatocellular carcinoma (HCC), and their impact on receipt of cancer care. Methods: A retrospective cohort study was performed of all veterans diagnosed with HCC at the William S. Middleton Memorial Veterans' Hospital in Madison, Wisconsin, whose tumor care was coordinated through a multidisciplinary tumor board. Outcomes included receipt of any HCC-specific therapy and overall survival. Results: From January 1, 2007, through December 31, 2016, 149 veterans were diagnosed with HCC. Substance use disorders were reported in 124 (83%) patients, psychiatric illness was documented in 55 (37%) patients, 23 (15%) patients had incomes below the poverty threshold, and 7 (5%) were experiencing homelessness. The mean (SD) distance traveled for care was 207.1 (277.9) km; travel and lodging assistance were accessed by 50 (34%) and 33 (22%) veterans, respectively. Seventy-one patients (48%) had HCC exceeding T2 stage at diagnosis. Curative treatment was offered to 78 (52%) patients, with 127 (85%) receiving any HCC-specific care. Median survival from diagnosis was 727 days (95% CI, 488-966). Conclusions: Psychosocial barriers were common in our veteran cohort. Individualizing care, and coordination of travel and lodging, assisted in enabling high rates of receipt of HCC-specific therapy and improving patient survival.

Provider Attitudes Toward Risk-Based Hepatocellular Carcinoma Surveillance in Patients With Cirrhosis in the United States.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) surveillance rates are suboptimal in clinical practice. We aimed to elicit providers' opinions on the following aspects of HCC surveillance: preferred strategies, barriers and facilitators, and the impact of a patient's HCC risk on the choice of surveillance modality. METHODS: We conducted a web-based survey among gastroenterology and hepatology providers (40% faculty physicians, 21% advanced practice providers, 39% fellow-trainees) from 26 US medical centers in 17 states. RESULTS: Of 654 eligible providers, 305 (47%) completed the survey. Nearly all (98.4%) of the providers endorsed semi-annual HCC surveillance in patients with cirrhosis, with 84.2% recommending ultrasound ± alpha fetoprotein (AFP) and 15.4% recommending computed tomography (CT) or magnetic resonance imaging (MRI). Barriers to surveillance included limited HCC treatment options, screening test effectiveness to reduce mortality, access to transportation, and high out-of-pocket costs. Facilitators of surveillance included professional society guidelines. Most providers (72.1%) would perform surveillance even if HCC risk was low (≤0.5% per year), while 98.7% would perform surveillance if HCC risk was ≥1% per year. As a patient's HCC risk increased from 1% to 3% to 5% per year, providers reported they would be less likely to order ultrasound ± AFP (83.6% to 68.9% to 57.4%; P < .001) and more likely to order CT or MRI ± AFP (3.9% to 26.2% to 36.1%; P < .001). CONCLUSIONS: Providers recommend HCC surveillance even when HCC risk is much lower than the threshold suggested by professional societies. Many appear receptive to risk-based HCC surveillance strategies that depend on patients' estimated HCC risk, instead of our current "one-size-fits all" strategy.

Management of hepatocellular carcinoma recurrence after liver transplantation.

Despite careful selection for liver transplantation (LT) of patients with hepatocellular carcinoma (HCC), HCC may still recur after LT and is frequently associated with dismal outcome. Tumor factors, including serum alpha-fetoprotein (AFP), the presence of microvascular invasion, tumor grade/differentiation, and largest tumor size are amongst the most important predictors of recurrence after transplantation. The nature of recurrence can be highly variable, but often presents with extra-hepatic involvement. As such, management of patients with HCC can be challenging, and consensus guidelines are lacking. Curative options, with surgery or ablation, which may be applicable in patients with isolated intra-or extrahepatic metastases, offer the best chance for improved long-term outcome in patients with HCC recurrence after transplantation. Most patients with recurrence have unresectable disease, and may benefit from palliative treatments, including intra-arterial therapies and/or systemic therapy.

Evaluation of pattern of bacterial contamination of outpatient department table surfaces in relation to cleaning and disinfection practices in a tertiary care hospital in Ahmedabad.

BACKGROUND: Outpatient department (OPD) table surfaces frequently touched by patients and health-care workers in hospitals harbor potential pathogens and may act as source of infectious agents. OBJECTIVES: This study aimed to determine the pattern of bacterial contamination of surfaces of OPD tables in relation to existing cleaning/disinfection practices. METHODS: The descriptive study was conducted during July 2018-September 2018. A total of 128 swabs were collected from 32 OPD table surfaces immediately after cleaning or disinfection and then at 30 min, 2 h, and 4 h interval after cleaning or disinfection. Type and concentration of cleaner or disinfectant, number of cleaning strokes on table, and time of last washing of cleaning cloth with detergent were also noted from each location. Isolation, identification, and antibiotic susceptibility testing of the isolates were performed by standard microbiological techniques. RESULTS: A total of 337 bacterial isolates were recovered from 126 samples. Multidrug resistant Staphylococci, Acinetobacter, Pseudomonas, Klebsiella, and Escherichia coli were isolated. The mean bacterial colony count increased with time (P < 0.0001). Hand rub use, cleaning of OPD table surfaces with disinfectant, and more number of strokes with cleaning cloth resulted in decrease in colony count of bacteria isolated. CONCLUSION: High bacterial contamination of frequently touched OPD table surfaces with variety of potential pathogens like Staphylococcus, Acinetobacter, Pseudomonas, Klebsiella, and E. coli was detected. Hand hygiene among health-care workers and regular and frequent cleaning and disinfection of OPD table surfaces are highly recommended to prevent cross-transmission.

Genetic Variations Linked to Hepatocellular Carcinoma: Personalized Medicine Takes a Step Forward.

: There are strong associations between candidate genetic polymorphisms associated with intrahepatocyte lipid droplet accumulation and the development of cirrhosis, via a common sequence in which lipid accumulation is followed by chronic inflammatory injury and fibrogenesis. Hepatocellular carcinoma (HCC) has also been linked to genetic polymorphisms associated with intracellular lipid trafficking, although, as shown in the present study, not all the candidate polymorphisms implicated in fibrogenesis are also tied to HCC. Genetic analysis may identify at-risk persons who would most benefit from modifying life-style factors linked to cirrhosis and HCC, and also persons most likely to benefit from HCC surveillance.

Identification of prevalent dengue serotypes by reverse transcriptase polymerase chain reaction and correlation with severity of dengue as per the recent World Health Organization classification (2009).

Context: A definite link between distinct dengue serotypes and severe clinical manifestations has not been established yet. The WHO classification (2009) of dengue is more competent in diagnosing severe cases compared to traditional (1997) classification. Aims: This study aimed to identify prevalent dengue serotypes and to correlate the severity of dengue with the dengue virus (DENV) serotypes in target population as per the recent WHO classification (2009). Settings and Design: A retrospective comparative observational study was conducted from 1st January 2015 to 31st December 2015. Subjects and Methods: We tested 242 dengue NS-1 antigen ELISA-positive cases for serotyping by dengue reverse transcriptase-polymerase chain reaction (RT-PCR). Severity of each dengue case confirmed by RT-PCR was determined as per the recent WHO classification (2009). Results: On the basis of RT-PCR, dengue infection was confirmed in 135 (55.78%) patients. DEN-3 was the most common serotype found in 71 (52.6%) patients, followed by DEN-2 serotype with 44 (32.6%) patients. Nearly 2.22% cases of DEN-2 and 2.96% cases of DEN-3 serotype were having dengue with warning signs. Severe dengue was found in 2.22% cases of DEN-2 and 5.18% cases of DEN-3 serotypes. Thrombocytopenia, haemorrhagic manifestations and atypical presentations were found most commonly in DEN-3 followed by DEN-2 serotype. Coinfection with more than one serotype was observed in our study, with the most common coinfection pattern being DEN-2 and DEN-3 serotypes. Conclusions: DENV-3 and DENV-2 serotypes are prevalent in the region and are associated with a more serious clinical profile than other serotypes.

A case of syphilitic hepatitis in an HIV-infected patient.

While the incidence of syphilis has been persistently on the rise in the United States, hepatitis as a complication of early syphilis is relatively uncommon. We present a case of a 51-year-old homosexual, HIV-positive man who presented with acute cholestatic hepatitis with a predominantly elevated alkaline phosphatase. After laboratory studies and imaging were unrevealing, a liver biopsy was performed that showed expanded portal tracts with a predominantly lymphoplasmacytic infiltrate and prominent bile ductular proliferation with periductal neutrophils. Testing revealed a positive rapid plasma reagin, and a subsequent Warthin-Starry stain of the liver tissue demonstrated the presence of scattered spirochetes, confirmed as Treponema pallidum spirochetes on immunohistochemistry testing. These findings confirmed a diagnosis of syphilitic hepatitis. With therapy, symptoms and liver enzymes rapidly normalized. Given the persistent rise in syphilis incidence along with the morbidity and mortality associated with a missed diagnosis, keen suspicion, early identification, and treatment are crucial.

Evaluation of concurrent malaria and dengue infections among febrile patients.

CONTEXT: Despite a wide overlap between endemic areas for two important vector-borne infections, malaria and dengue, published reports of co-infections are scarce till date. AIMS: To find the incidence of dengue and malaria co-infection as well as to ascertain the severity of such dengue and malaria co-infection based on clinical and haematological parameters. SETTING AND DESIGN: Observational, retrospective cross-sectional study was designed including patients who consulted the tertiary care hospital of Ahmedabad seeking treatment for fever compatible with malaria and/or dengue. SUBJECTS AND METHODS: A total of 8364 serum samples from clinically suspected cases of fever compatible with malaria and/or dengue were collected. All samples were tested for dengue NS-1 antigen before 5 days of onset of illness and for dengue IgM after 5 days of onset of illness. In all samples, malaria diagnosis was based on the identification of Plasmodium parasites on a thin and thick blood films microscopy. RESULTS: Only 10.27% (859) patients with fever were tested positive for dengue and 5.1% (434) were tested positive for malaria. 3.14% (27) dengue cases show concurrent infection with malarial parasites. Hepatomegaly and jaundice 37.03% (10), haemorrhagic manifestations 18.51% (5) and kidney failure 3.7% (1), haemoglobin <12 g/dl 100% (27) and thrombocytopenia (platelet count <150,000/cmm) 96.29% (26) were common in malaria and dengue co-infections and were much more common in Plasmodium falciparum infections. CONCLUSION: All febrile patients must be tested for malaria and dengue, both otherwise one of them will be missed in case of concurrent infections which could lead to severe diseases with complications.

Multidisciplinary Management of Hepatocellular Carcinoma Improves Access to Therapy and Patient Survival.

BACKGROUND: Given the complexity of managing hepatocellular carcinoma (HCC), it is widely accepted that a multidisciplinary team approach (tumor boards) offers the best approach to individualize therapy. The aim of this study was to determine utilization of therapies and outcomes for patients with HCC, comparing those managed through our multidisciplinary tumor board (MDTB) to those who were not. METHODS: A database analysis of all patients with HCC managed through our MDTB, from 2007 until 2011, was performed. A database of all patients with HCC from 2002 to 2011, not managed through MDTB, was similarly created. RESULTS: A total of 306 patients with HCC, from 2007 to 2011 were managed through our MDTB, in comparison with 349 patients, from 2002 to 2011 who were not. There were no significant differences in baseline demographic data or model for end-stage liver disease at presentation. Patients managed through MDTB were more likely to present at an earlier tumor stage and with lower serum alpha fetoprotein (AFP) (P=0.007). The odds of receiving any treatment for HCC was higher in patients managed through MDTB (odds ratio, 2.80; 95% confidence interval, 1.71-4.59; P<0.0001) independent of model for end-stage liver disease score, serum AFP, and tumor stage. There was significantly greater survival of patients managed through MDTB (19.1±2.5 vs. 7.6±0.9 mo, P<0.0001). Independent predictors for improved survival included management through MDTB, receipt of any HCC treatment, lower serum AFP, receipt of liver transplant, and T2 tumor stage. CONCLUSIONS: Patients with HCC managed through a MDTB had significantly higher rates of receipt of therapy and improved survival compared with those who were not.

The Utilization of Palliative Care Services in Patients with Cirrhosis who have been Denied Liver Transplantation: A Single Center Retrospective Review

ABSTRACT Introduction and aim. Utilization of palliative care services in patients dying of end-stage liver disease (ESLD) is understudied. We performed a retrospective review of palliative care services among patients with ESLD unsuitable for liver transplantation (LT) at a tertiary care center. Material and methods. Deceased ESLD patients considered unsuitable for LT from 2007-2012 were identified. Patients were excluded if they received a transplant, had an incomplete workup, were lost to follow up or whose condition improved so LT was not needed. Of the 1,175 patients reviewed, 116 met inclusion criteria. Results. Forty patients (34.4%) received an inpatient palliative care (PC) consultation and forty-one patients (35.3%) were referred directly to hospice. Thirty-three patients (28.4%) transitioned to comfort measures without PC consultation (median survival < 1 day). The median interval between LT denial and PC consultation or hospice was 28 days. Median survival after PC consult or hospice referral was 15 days. In conclusion, in a single center retrospective review of ESLD patients, palliative care services, when utilized, were for care at the very end of life. Without consultation, aggressive interventions continued until hours before death. We propose that ESLD patients could benefit from PC consultation at time of LT evaluation or based on MELD scores.

The Utilization of Palliative Care Services in Patients with Cirrhosis who have been Denied Liver Transplantation: A Single Center Retrospective Review.

INTRODUCTION AND AIM: Utilization of palliative care services in patients dying of end-stage liver disease (ESLD) is understudied. We performed a retrospective review of palliative care services among patients with ESLD unsuitable for liver transplantation (LT) at a tertiary care center. MATERIAL AND METHODS: Deceased ESLD patients considered unsuitable for LT from 2007-2012 were identified. Patients were excluded if they received a transplant, had an incomplete workup, were lost to follow up or whose condition improved so LT was not needed. Of the 1,175 patients reviewed, 116 met inclusion criteria. RESULTS: Forty patients (34.4%) received an inpatient palliative care (PC) consultation and forty-one patients (35.3%) were referred directly to hospice. Thirty-three patients (28.4%) transitioned to comfort measures without PC consultation (median survival < 1 day). The median interval between LT denial and PC consultation or hospice was 28 days. Median survival after PC consult or hospice referral was 15 days. In conclusion, in a single center retrospective review of ESLD patients, palliative care services, when utilized, were for care at the very end of life. Without consultation, aggressive interventions continued until hours before death. We propose that ESLD patients could benefit from PC consultation at time of LT evaluation or based on MELD scores.

Thanatophoric dysplasia type I: a rare case report at fetal autopsy.

Thanatophoric dysplasia type 1 is a lethal congenital anomaly with skeletal dysplasia. It is characterized by short limb dwarfism, enlarged head with frontal bossing, short neck, protuberant abdomen. It is detected in early gestational period by ultrasonography. The other associated anatomical abnormalities and characteristic laboratory findings aid in the early diagnosis and further work-up.

Atypical presentation of visceral leishmaniasis in a HIV-positive patient from a nonendemic area.

Visceral leishmaniasis (VL), though widely prevalent in India, is not seen in the Rajasthan where the dry, hot and arid climatic conditions create a hostile environment for the growth of the parasite or its vector, the sandfly. We present a case of VL in a patient co-infected with HIV from this region. A 34-year-old known case of a HIV-positive patient presented to the skin department of our hospital with multiple, nontender, erythematous, papulonodular lesions all over the body for 6 months with history of weight loss and low-grade fever. Important examination findings were pallor, inguinal lymphadenopathy and hepatosplenomegaly. Laboratory findings included anemia, leucopenia, hypergammaglobulinemia and altered leucocytes to erythrocyte ratio. Buffy coat examination and bone marrow aspirates showed the presence of leishman bodies inside monocytes and macrophages respectively as well as extracellularly also. The patient was treated with amphotericin B intravenously and responded well to the treatment.

2-Azetidinone--a new profile of various pharmacological activities.

2-azetidinone, a ß-lactam four member heterocyclic compound involved in research aimed to evaluate new products that possess interesting biological activities. These compounds reported for their antimicrobial and antifungal activities. Successful introduction of aztreonam as a potent inhibitor of cephalosporinase and ezetimibe as a cholesterol absorption inhibitor proved potential of 2-azetidinone moiety. Subsequently 2-azetidinones were highlighted as a potent mechanism based inhibitor of several enzymes like human tryptase, chymase, thrombin, leukocyte elastase, human cytomegalovirus protease and serine protease enzyme. These derivatives also known to possess antitubercular, anti-inflammatory, antitumor, anti-HIV, antiparkinsonian, antidiabetic and vasopressin V1a antagonist activity. The present review article focuses on the pharmacological profile of 2-azetidinones with their potential activities.

Isolation of Aspergillus nidulans from a case of fungal rhinosinusitis: a case report.

A rare species i.e. A. nidulans is reported as a causative agent of allergic fungal rhinosinusitis in this study. It is an increasingly recognized type of chronic recurring hypertrophic sinus disease. There are more than 185 species of aspergillus and over 95% of all infections are caused by A. fumigatus, A. flavus and A. niger. A. fumigatus alone accounts for the large majority of cases of both invasive and non invasive aspergillosis. A young immunocompetent lady presented with bilateral nasal obstruction due to multiple polypoid mass at Sheth Vadilal Sarabhai General Hospital, Ahmedabad. Provisional diagnosis of sinonasal polyposis possibly due to fungal cause with infiltration in to nasal cavity was made. Bilateral functional endoscopic sinus surgery with polypectomy was done. The specimen was examined by standard methods and the fungus was identified as A. nidulans by slide culture.

Isolation of Vibrio mimicus from a case of acute diarrhoea--a case report.

Over a four months period (June to September, 2003) 111 stool samples from cases of acute diarrhoea were screened for Vibronaceae in department of microbiology, Smt. N. H. L. Municipal medical college, Ahmedabad. All the isolates were identified by standard laboratory technique. A total of 36 species belonging to Vibrionaceae were isolated. Phage typing of all these Vibronaceae were done at National Institute Of Cholera and Enteric Disease, Kolkata. Out of 36 isolates, 35 were Vibrio cholereae and only one was Vibrio mimicus. We report this case because of rare strain.

Characterization of dendritic cells generated in vivo by an E. coli derived chimeric dual receptor agonist.

BACKGROUND: Progenipoietin-4 (ProGP-4) is an E. coli derived chimeric growth factor that activates the human Flt3 and G-CSF receptors. ProGP-4 possesses cross-species activity and treatment of mice with ProGP-4 results in increases in the number of WBC and Class II+/CD11c+ cells in both spleen and peripheral blood. Herein, we report morphologic, phenotypic and functional evaluation of Class II+/CD11c+ cells generated by in vivo administration of ProGP-4. MATERIAL/METHODS: C57BL/6 mice were injected daily with ProGP for 7 to 18 days. Leukocytes from spleen and peripheral blood were analyzed by flow cytometry to enumerate and characterize changes in DC populations. Spleens from ProGP treated mice were evaluated by immunocytochemistry and enriched CD11c+ populations were functionally assessed in a mixed lymphocyte assay and in an antigen dependent CTL assay. RESULTS: Administration of this dual receptor agonist to mice resulted in dose-dependent increases in the numbers of total white blood cells and Class II+/CD11c+ cells in spleen and peripheral blood. CD11c+ cells from ProGP-4 treated mice co-expressed DEC205 and also expressed CD80, CD86 and CD40, albeit at lower levels as compared to Class II+/CD11c+ cells from untreated animals. Despite lower co-stimulatory molecule expression, ProGP-4-generated Class II+/CD11c+ cells stimulated proliferation of allogeneic T cells and an antigen-specific T cell hybridoma as efficiently as bone marrow derived dendritic cells from untreated mice. CONCLUSIONS: The data presented in this report highlight the ability of E. coli derived ProGP-4 to expand large numbers of functional DC in the peripheral blood and lymphoid organs in vivo using a rodent model of hematopoiesis. E. coli derived chimeric receptor agonists such as ProGP-4 may enable further investigations of immunotherapeutic approaches to the treatment of diseases such as cancer and autoimmunity.

Enhanced ability of the progenipoietin-1 to suppress apoptosis in human hematopoietic cells.

Repopulating hematopoietic cell compartments after myeloablative chemotherapy remains a key factor in a successful chemotherapy program. Modified and chimeric cytokines have been developed to help reduce inflammation, fever and hospitalization time for patients. A chimeric cytokine, progenipoietin-1 (ProGP-1), containing the G-CSF and FL receptor agonists binds both the G-CSF receptor and FLT-3. It also stimulates the growth of dendritic cells, which play an important role in immunotherapy. While in vivo effects of ProGP-1 are well described, the mechanisms by which it stimulates growth are not well understood. We have investigated the effects of ProGP-1 on prevention of apoptosis in the human hematopoietic cell line OCI-AML.5. ProGP-1 promoted cellular proliferation better than G-CSF or FL separately but stimulated proliferation similar to their co-addition as demonstrated by growth curves and [3H]-thymidine incorporation. ProGP-1 prevented apoptosis to a greater degree than G-CSF or FL alone as determined by annexin V/propidium iodide binding and TUNEL assays. ProGP-1 promoted maintenance of the mitochondrial membrane potential better than G-CSF or FL alone. In addition, Pro-GP promoted a lower redox potential as higher levels of free radicals were detected after cytokine treatment than in cytokine-deprived cells implying increased respiration. These data indicate that ProGP-1 promotes the proliferation and prevents the apoptosis of human hematopoietic cells better than FL or G-CSF alone, and to a similar extent as their co-addition. Thus, ProGP-1 can be used to repopulate certain hematopoietic cells as a single entity rather than the introduction of two different cytokines.