Intestinal obstruction induced by portal vein thrombosis in a female undergoing oral contraceptive therapy: a case report with comprehensive review.

Introduction: Portal vein thrombosis (PVT) is a rare medical condition that obstructs blood flow in the portal vein, with cirrhosis as a common predisposing factor. However, its association with oral contraceptive pills (OCPs), particularly with progestins, remains inadequately explored. This case report aims to contribute to this understanding, focusing on the rare presentation of PVT-induced intestinal obstruction in a female on prolonged OCP therapy. Case presentation: A 45-year-old female presented with severe abdominal pain, vomiting, and constipation. Diagnosis revealed PVT-induced intestinal obstruction, an exceptionally rare occurrence in the context of prolonged OCP therapy. The patient's symptoms improved with conservative management, including rivaroxaban, highlighting the crucial role of early intervention. Discussion: This case brings attention to the limited literature exploring the link between OCPs and PVT. Despite the generally safe reputation of OCPs, they can induce pro-thrombotic conditions, emphasizing the need for heightened clinical awareness. In this case, the rarity of intestinal obstruction in PVT, compounded by the absence of common risk factors, underscores the diagnostic challenges associated with such presentations. Conclusion: PVT-induced intestinal obstruction in a patient on prolonged OCP therapy is exceptionally rare, emphasizing the necessity for multidisciplinary management. It provides crucial insights into suspecting, identifying, and treating this uncommon complication in non-cirrhotic individuals, contributing to the limited existing literature on the subject.

FPGA Implementation of IIR Notch and Anti-Notch Filters With an Application to Localization of Protein Hot-Spots.

In this paper, high-speed second-order infinite impulse response (IIR) notch filter (NF) and anti-notch filter (ANF) are designed and realized on hardware. The improvement in speed of operation for the NF is then achieved by using the re-timing concept. The ANF is designed to specify a stability margin and minimize the amplitude area. Next, an improved approach is proposed for the detection of protein hot-spot locations using the designed second-order IIR ANF. The analytical and experimental results reported in this paper show that the proposed approach provides better hot-spot prediction compared to the reported classical filtering techniques based on the IIR Chebyshev filter and S-transform. The proposed approach also yields consistency in prediction hot-spots compared to the results based on biological methodologies. Furthermore, the presented technique reveals some new "potential" hot-spots. The proposed filters are simulated and synthesized using the Xilinx Vivado 18.3 software platform with Zynq-7000 Series (ZedBoard Zynq Evaluation and Development Kit xc7z020clg484-1) FPGA family.

Optimization of lateral flow assay for Canine morbillivirus detection and the application of the strip as sample substitute.

Canine distemper is an emerging disease, caused by the Canine morbillivirus (CDV) of the Paramyxoviridae family. The virus has evolved as a multi-host pathogen as it affects many wildlife animal species. The development of specific and sensitive diagnostic tests is the need for a control program. Several diagnostic tests are available for the detection of CDV antigen and antibody. Lateral flow assay (LFA) is the most promising point of care diagnostic test because of its specificity, easy use, and instant result. This study was designed to develop a lateral flow assay using the in-house developed monoclonal antibody (mAb) against the nucleocapsid protein (N) of the 'CDV/dog/bly/Ind/2018' isolate, which represents the circulating strains of India. The two mAbs included in the study showed high binding affinity in indirect ELISA and dot blot assay. Out of two, one mAb was selected due to its comparatively higher binding affinity in LFA format, and less non-specific binding to the biological matrix and buffer components. The limit of detection was found to be 106.5 TCID50/ml with the assay run time of 5 min. The fresh clinical samples collected on the spot were distinctly detected by the LFA, whereas the stored samples with a reduced titre of the virus showed inconsistent results. Moreover, the blood samples showed a clear distinction of positive and negative than the swab and tissue homogenates. The RNA extraction from the strip was successful with the some modifications in the Trizol RNA extraction method and the N and H gene fragments were amplified. Therefore, the study concludes that the LFA is suitable for CDV antigen detection in the field conditions and the strips can be used as the sample substitute for molecular study.

Japanese Encephalitis Virus Genotype III Strains Detection and Genome Sequencing from Indian Pig and Mosquito Vector.

Japanese encephalitis viruses (JEVs) are globally prevalent as deadly pathogens in humans and animals, including pig, horse and cattle. Japanese encephalitis (JE) still remains an important cause of epidemic encephalitis worldwide and exists in a zoonotic transmission cycle. Assam is one of the highly endemic states for JE in India. In the present study, to understand the epidemiological status of JE circulating in pigs and mosquito, particularly in Assam, India, molecular detection of JEV and the genome sequencing of JEV isolates from pigs and mosquitoes was conducted. The genome analysis of two JEV isolates from pigs and mosquitoes revealed 7 and 20 numbers of unique points of polymorphism of nucleotide during alignment of the sequences with other available sequences, respectively. Phylogenetic analysis revealed that the isolates of the present investigation belong to genotype III and are closely related with the strains of neighboring country China. This study highlights the transboundary nature of the JEV genotype III circulation, which maintained the same genotype through mosquito-swine transmission cycles.

Development of multiplex PCR assay for simultaneous detection of African swine fever, porcine circo and porcine parvo viral infection from clinical samples.

A diagnostic method for simultaneously detecting and distinguishing African Swine Fever (ASF), porcine circovirus type 2 (PCV2), and porcine parvovirus (PPV) in clinical specimens is critical for differential diagnosis, monitoring, and control in the field. Three primer pairs were designed and used to create a multiplex PCR assay. In addition, 356 porcine post mortem tissue samples from various parts of India's North Eastern region were tested by the developed multiplex PCR assay to demonstrate its accuracy. Using the designed primers, each of the ASF, PCV2 and PPV target genes was amplified, but no other porcine virus genes were detected. The assay's limit of detection was 102 copies/µl of PCV2, PPV, or ASFV. The detection of PCV2, PPV, and ASF in postmortem tissue samples revealed that they are co-circulating in India's North-Eastern region. The percentage positivity (PP) for PCV2, PPV and ASF single infection were 7.02% (25/356), 3.93% (14/356), and 3.37% (12/356), respectively, while the PP for PCV2& PPV co-infection was 2.80% (10/356), ASF & PCV2 co infection was 1.4% (5/356) and the ASF, PPV& PCV2 co-infection was1.40% (5/356). The results also indicate that the ASF can infect pigs alongside PCV and PPV.

Development of CD163 receptor-based enzyme-linked immunosorbent assay for diagnosis of porcine reproductive and respiratory syndrome virus.

Porcine reproductive and respiratory syndrome (PRRS) is an important economical disease in the global swine industry. The accurate detection of the PRRS virus (PRRSV) antigen is essential for the disease control and prevention programme. In this study, an indirect enzyme-linked immunosorbent test (PRRSVCD163-iELISA) was developed for the detection of the PRRSV antigen in samples of post-mortem swine tissue using the recombinant pig CD163 receptor protein as the capture ligand. The test was found to be specific for PRRSV, with no cross-reactions with other prevalent pig viral pathogens. The assay was validated by testing 217 post-mortem porcine tissue samples and the results were found to be satisfactory with a relative accuracy of 88.88%. Our assay is also quite precise, with intra- and inter-assay CVs of 6% and 10%, respectively. These findings imply that the PRRSVCD163-iELISA developed is capable of detecting the PRRSV antigen in swine post-mortem tissue samples. This research showed that porcine CD163, the PRRSV cellular receptor, can be exploited to build a diagnostic technique for the detection of PRRSV antigen. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03376-z.

A prospective, multicenter, clinical Study to evaluate the Safety, Pharmacokinetics, and Efficacy of Bleed Outcomes, with HemoRel-A® in severe Hemophilia A Patients.

PURPOSE: To evaluate efficacy for an on-demand treatment of acute bleeding events, pharmacokinetics, safety, and tolerability of HemoRel-A® in severe hemophilia A. METHODS: A total of 44 male subjects with severe hemophilia A with an annualized bleed rate of 12 while on-demand treatment with factor VIII (FVIII) were enrolled in the study and received HemoRel-A® for bleed treatment. The efficacy of HemoRel-A® was evaluated based on a four-point scale (excellent, good, moderate, or none). Six-point pharmacokinetic (PK) assessment was performed following a single dose of 50 IU/kg in 12 subjects after a 7-day wash-out period. Safety evaluations were performed at each visit and inhibitor testing was performed in all patients at screening and end of study. RESULTS: Forty-four male subjects received at least a single dose of the study medication and were included in the intent-to-treat (ITT) analysis and safety outcome. In 23 (7.52%) out of the 306 bleeding events, HemoRel-A® efficacy was rated as excellent, in 272 (88.89 %) bleeds it was rated as good, and in 11 (3.68%) bleeding events it was rated as moderate. No failure of efficacy was noted in any of the bleeding events. Thus overall out of 306 bleeding events, 295 (96.41%) showed excellent or good efficacy. Pharmacokinetic assessment based on plasma FVIII activity measured by the chromogenic assay in 12 patients showed comparative results similar to FVIII preparations. A total of 12 adverse events (AEs) were reported in this study. There was no inhibitor development in this previously treated patients (PTP) cohort. CONCLUSION: HemoRel-A® was established to be efficacious and safe in the treatment of acute bleeding events in subjects with severe hemophilia A. TRIAL REGISTRATION NUMBER: CTRI/2018/05/013790. Registration date: 9th May 2018.

Porcine Circovirus type 2 infected myocardial tissue transcriptome signature.

The goal of this study was to compare the global gene expression profile in cardiac tissues of pig infected with porcine circovirus 2 (PCV2) to that of healthy cells. Since PCV2 infection causes severe cardiovascular lesions, the myocardial tissue model was chosen for this study. In High-throughput transcriptome analysis, DESeq2 and CLC genomics workbench analyses revealed a total of 196 significantly differentially expressed genes (DEGs) (p-value < 0.05). Furthermore, 194 transcripts were upregulated, while only two were downregulated (HSPA6 and DNAJA1), with fold changes ranging from 16.293 to -10.002. Among the KEGG canonical pathways targeted by the DEGs in the functional analysis, adrenergic signalling in cardiomyocytes, Cardiac Muscle Contraction, Hypertrophic Cardiomyopathy (HCM), and Dilated Cardiomyopathy (DCM) tends to be enriched. The differentially expressed highly connected (DEHC) biomarker genes in pathogenicity of PCV2 infection, such as LDB3, MYOZ2, CASQ2, TNNT2, MLC2V, MYBPC3, ACTC1, TCAP, TNNI3, TRDN, CSRP3, MYL3, RYR2, LMOD2, MYH7, etc., were identified using protein-protein interaction (PPI) network analysis. The study might provide detailed information on the dysregulated genes and biological pathways in infected myocardial tissues that may be essential for PCV2-related heart pathology.

Lumbar Disc Degenerative Disorder among Patients Undergoing Magnetic Resonance Imaging in a Tertiary Care Centre: A Descriptive Cross-sectional Study.

Introduction: Magnetic resonance imaging is the standard imaging modality for detecting disc pathology due to its advantage of lack of radiation, multiplanar imaging capability, excellent spinal soft-tissue contrast, and precise localization of intervertebral discs changes. The aim of the study is to find out the prevalence of lumbar disc degenerative disorder among patients undergoing magnetic resonance imaging in a tertiary care hospital. Methods: A descriptive cross-sectional study was conducted in the Department of Radiodiagnosis and Interventional Radiology of a tertiary care centre among patients with complaints of low back pain from 24th May, 2021 to 31st December, 2021 in a tertiary care hospital. Ethical clearance was taken from the Institutional Review Committee (Reference number: 134/2077-78). A sample size of 899 was taken and convenience sampling was done. Collected data were entered and analyzed on Statistical Package for the Social Sciences version 22.0. Point estimate at 95% Confidence Interval was calculated along with frequency and percentage for binary data and mean with standard deviation for continuous data. Results: Among 899 patients undergoing magnetic resonance imaging, the prevalence of lumbar disc degenerative disorder was found to be 155 (17.24%) (14.77-19.70 at 95% Confidence Interval). Conclusions: The prevalence of lumbar disc degenerative disorder among patients undergoing magnetic resonance in our study was lower when compared to other similar studies conducted in similar settings. Keywords: disc degeneration; low back pain; magnetic resonance imaging.

Synovial Chondromatosis of Hip Joint in a Patient with Ankylosing Spondylitis: A Case Report.

Synovial chondromatosis in association with ankylosing spondylitis is extremely rare and has been reported only once before and this case report is presenting a similar case. The knee is the preferential site of involvement with involvement of the hip being reported sparsely. We herein report a case of a 52-year-old male who came with complaints of the lower back pain for 5 years and left hip pain for 1.5 years who was diagnosed with synovial chondromatosis of the hip joint with axial ankylosing spondylitis and was managed operatively. We here review briefly the clinical manifestations, pathogenesis, diagnosis, previously reported cases as well as treatment of synovial chondromatosis in patients with immune-mediated inflammatory arthritides. There should be a high index of suspicion to diagnose synovial chondromatosis in association with inflammatory arthritides. We also believe that surgical management is an effective method of treatment of an established synovial chondromatosis of the hip joint. Keywords: ankylosing spondylitis; case reports; hip joint; synovial chondromatosis.

Effect of fuel preheating on performance, emission and combustion characteristics of a diesel engine fuelled with Vateria indica methyl ester blends at various loads.

The present study examines the preheated (95 °C) and unheated (35 °C) Vateria indica methyl ester (VIME) blends by studying the engine performance, combustion, and emission characteristics at various loads. A single-cylinder, TV1 Kirloskar direct injection diesel engine is used to carry out the tests. Biodiesel produced from Dhupa fat through the transesterification process is used as a renewable fuel in a diesel engine. In this work, diesel (B0), VIME (B100), and two binary blends (B30 and B50) are used. VIME has a higher viscosity, higher density, and lower calorific value than diesel, resulting in lesser brake thermal efficiency (BTE) and higher brake specific energy consumption (BSEC). Due to high viscosity of the biodiesel, preheating of fuel is done before injecting into cylinder. Preheating reduces the viscosity, and enhances the atomization and vaporization of fuel, resulting in improved engine performance. For a given blend of VIME biodiesel and diesel, the preheated blend has better BTE, decreased BSEC and lesser CO and HC emissions, with a slight increment in NOX emission compared to the unheated blend. The preheated B30 blend has a BTE value of 30.3% which is close to the BTE value of 30.1% of unheated diesel at 100% load condition. CO, HC, and soot emissions are decreased by 16.2%, 34.4%, and 16.5%, respectively, for preheated B100 fuel compared to unheated B100, at full load.

Caregiver Burden in Caregivers of Stroke Survivors: A Hospital-Based Study.

Background: A principal caregiver (CG) is directly affected by the patient's health problems leading to CG strain. In the present study, we evaluated the different factors related to increased CG burden in stroke survivors and assessed the relationship between patient's personal and clinical characteristics and CG's stress. Material and Methods: In this prospective, follow-up study, a total of 141 principle CGs of 164 First-ever stroke (FES) survivors were subjected to the Caregivers Strain Index (CSI) and Oberst Caregiving Burden Scale (OCBS) at 30 days (n = 141), 90 days (n = 129), and 6 months (n = 119) after informed consent. Patients were subjected to modified Rankin Scale (mRS) and Barthel index score assessment at the end of 30 days. Results: The mean age of CG was 49.8 ± 21.0 years, approximately 20 years lesser than that of the patients. 102 (72.34%) CGs were females. Urinary incontinence (p < 0.006) morbidity at 30 days, mRS (p = 0.004), and moderate to the severe neurological deficit on admission (p = 0.003) were the patient factors in FES cases leading to significant CGs stress. CG factors responsible for major stress were long caregiving hours (P < 0.001), anxiety (P < 0.001), disturbed night sleep (P < 0.001), financial stress (P < 0.001), younger age (P = 0.002), and CGs being daughters-in-law (P = 0.039). Conclusion: CG burden increases with increased severity of stroke. Integrated stroke rehabilitation services should also address CGs issues along with patients.

Foraminal Stenosis at L5-S1 as an Overlooked Pathology of Bilateral Radiculopathy: A Case Series.

Introduction: The classical symptom of foraminal stenosis is unilateral radiculopathy. Bilateral radiculopathy caused purely by foraminal stenosis is rare. Here, we report five cases of bilateral L5 radiculopathy caused purely by L5-S1 foraminal stenosis and describe the clinical and radiological features of these patients in detail. Case Presentation: Among the five patients, two were men and three were women with an average age of 69 years. Four patients had undergone surgeries at L4-5 level, previously. All the patients showed an improvement in symptoms in the post-operative period. After a certain period, the patients complained of bilateral leg pain and numbness. An additional surgery was performed in two patients; however, there was no improvement in symptoms. One patient, who did not undergo surgery, was treated conservatively for 3 years. All the patients had been suffering from bilateral leg symptoms before their first visit to our hospital. The neurological findings in these patients were consistent with bilateral L5 radiculopathy. The average pre-operative Japanese Orthopedic Association (JOA) score was 13 out of 29 points. Bilateral foraminal stenosis at L5-S1 level was confirmed using a three-dimensional magnetic resonance imaging or computed tomography. Posterior lumbar interbody fusion was performed in one patient and bilateral lateral fenestration using Wiltse's approach was performed in four patients. The neurological symptoms recovered immediately after surgery. The average JOA score at 2-year follow-up was 25 points. Conclusions: Spine surgeons may overlook the pathology of foraminal stenosis, particularly in patients with bilateral radiculopathy. Familiarity with the clinical and radiological features of symptomatic lumbar foraminal stenosis is necessary to properly diagnose bilateral foraminal stenosis at L5-S1 level.

TLR22-mediated activation of TNF-α-caspase-1/IL-1ß inflammatory axis leads to apoptosis of Aeromonas hydrophila-infected macrophages.

Toll-like receptors (TLRs) represent first line of host defence against microbes. Amongst different TLRs, TLR22 is exclusively expressed in non-mammalian vertebrates, including fish. The precise role of TLR22 in fish-immunity remains abstruse. Herein, we used headkidney macrophages (HKM) from Clarias gariepinus and deciphered its role in fish-immunity. Highest tlr22 expression was observed in the immunocompetent organ - headkidney; nonetheless expression in other tissues suggests its possible involvement in non-immune sites also. Aeromonas hydrophila infection up-regulates tlr22 expression in HKM. Our RNAi based study suggested TLR22 restricts intracellular survival of A. hydrophila. Inhibitor and RNAi studies further implicated TLR22 induces pro-inflammatory cytokines TNF-α and IL-1ß. We observed heightened caspase-1 activity and our results suggest the role of TLR22 in activating TNF-α/caspase-1/IL-1ß cascade leading to caspase-3 mediated apoptosis of A. hydrophila-infected HKM. We conclude, TLR22 plays critical role in immune-surveillance and triggers pro-inflammatory cytokines leading to caspase mediated HKM apoptosis and pathogen clearance.

Clinical and oncological outcomes of surgery in Anorectal melanoma in Asian population: A 15 year analysis at a tertiary cancer institute.

INTRODUCTION: Anorectal malignant melanoma (ARMM) is an aggressive malignancy with dismal prognosis and a 5-year survival rate less than 20% in most of the previous studies. The ideal surgical treatment has still remained controversial. This retrospective study aims at analysing the outcome in patients with ARMM treated with curative surgical resection. PATIENTS AND METHODS: This is a retrospective study of 38 patients of stage I anorectal malignant melanoma treated with curative surgical resection at our tertiary cancer institute. RESULTS: WLE (Wide Local Excision) was carried out in 12 patients and APR (abdominoperineal resection) was done in 26 patients. The median overall survival of the entire group in this study was 20 months. Although the median overall survival of WLE patients was higher than those with APR (37 months versus 16 months, respectively), this was not a statistically significant event (P=0.317). The 1-, 2-, 3-, 5-year survival rates were similar with both APR and WLE with no significant difference in the 5-year survival rate (P=0.816); overall 5-year survival rate of just 13%. There were 3 long-term survivors in this study group who survived for more than 10 years. CONCLUSION: Most patients ultimately succumb to the disease regardless of the management. Both APR and WLE have significant roles in the management depending on the subset of patients selected. Local treatment should be preferred wherever possible. Abdominoperineal resection should be offered in nodal disease or in a recurrent setting.

Replication competence of canine distemper virus in cell lines expressing signaling lymphocyte activation molecule (SLAM) of goat, sheep and dog origin.

Cellular receptors play an important role in entry and cell to cell spread of morbillivirus infections. The cells expressing SLAM and Nectin-4 have been used for successful and efficient isolation of canine distemper virus (CDV) in high titre. There are several methods for generation of cells expressing receptor molecules. Here, we have used a comparatively cheaper and easily available method, pcDNA 3.1 (+) for engineering Vero cells to express SLAM gene of goat, sheep and dog origin (Vero/Goat/SLAM (VGS), Vero/Sheep/SLAM (VSS) and Vero/Dog/SLAM (VDS), respectively). The generated cell lines were then compared to test their efficacy to support CDV replication. CDV could be grown in high titre in the cells expressing SLAM and a difference of log two could be recorded in virus titre between VDS and native Vero cells. Also, CDV could be grown in a higher titre in VDS as compared to VGS and VSS. The finding of this study supports the preferential use of SLAM expressing cells over the native Vero cells by CDV. Further, the higher titre of CDV in cells expressing dog-SLAM as compared to the cells expressing SLAM of non-CDV hosts (i.e. goat and sheep) points towards the preferential use of dog SLAM by the CDV and may be a plausible reason for differential susceptibility of small ruminants and Canines to CDV.

Evaluation of ELISA and PCR in parallel to single intradermal cervical tuberculin test (SICT) for diagnosis of tuberculosis in buffaloes.

Bovine tuberculosis is an economically important disease with very high zoonotic potential. Single intradermal cervical tuberculin test (SICT) is considered a gold standard assay for the diagnosis of bovine tuberculosis. However, bovines especially buffaloes may produce a false negative result when the animal becomes cell-mediated immune (CMI) anergic in the advanced stage of the disease. In the present study, ELISA and PCR assays were successfully demonstrated to be useful in diagnosing tuberculosis especially in the CMI anergic buffaloes infected with Mycobacterium bovis. ELISA and PCR assays are able to detect 8.94% and 8.13%, respectively, more animals as positive in comparison to standard SICT assay in a selected population of 123 buffaloes. The moderate agreement between SICT and ELISA (k: 0.528; 0.249-0.807), a substantial agreement between SICT and PCR (k: 0.648; 0.364-0.931), and high agreement between ELISA and PCR (k: 0.856; 0.697-1.0) highlight that ELISA and PCR, if used in parallel with SICT, will provide better sensitivity over single assay. Reduction of false negative reactors may help in minimizing the zoonotic threat from bovine tuberculosis especially in disease endemic region where human and livestock interface is quite high.

Soft tissue aneurysmal bone cyst of left hemithorax with review of literature.

Soft tissue aneurysmal bone cysts (STABCs) are extremely rare extraosseous counterpart of aneurysmal bone cyst (ABC), with close resemblance to histo-morphologic characteristics of ABC. Here we would like to report a 13-year-old female patient, who presented with a large mass, occupying the entire left hemithorax. Patient underwent resection of the thoracic mass. On histopathological examination, it was found to be a soft tissue ABC. It is a very rare tumor and until date 28 cases have been reported in English literature, to the best of our knowledge. On review of the literature, we found this to be the first case of STABC reported in thoracic cavity. The objective of this case presentation is to provide information regarding clinical presentation, radiological and pathological features, and course of management for this rare disease. Soft tissue ABCs are a new class of tumors, so more extensive research is required to establish standard guidelines for their diagnosis and management, to yield better prognosis.

Advancement of nanoscience in development of conjugated drugs for enhanced disease prevention.

Nanoscience and nanotechnology is a recently emerging and rapid developing field of science and has also been explored in the fields of Biotechnology and Medicine. Nanoparticles are being used as tools for diagnostic purposes and as a medium for the delivery of therapeutic agents to the specific targeted sites under controlled conditions. The physicochemical properties of these nanoparticles give them the ability to treat various chronic human diseases by site specific drug delivery and to use in diagnosis, biosensing and bioimaging devices, and implants. According to the type of materials used nanoparticles can be classified as organic (micelles, liposomes, nanogels and dendrimers) and inorganic (including gold nanoparticles (GNPs), super-paramagnetic iron oxide nanomaterials (SPIONs), quantum dots (QDs), and paramagnetic lanthanide ions). Different types of nanoparticle are being used in conjugation with various types of biomoities (such as peptide, lipids, antibodies, nucleotides, plasmids, ligands and polysaccharides) to form nanoparticle-drug conjugates which has enhanced capacity of drug delivery at targeted sites and hence improved disease treatment and diagnosis. In this study, the summary of various types of nanoparticle-drug conjugates that are being used along with their mechanism and applications are included. In addition, the various nanoparticle-drug conjugates which are being used and which are under clinical studies along with their future opportunities and challenges are also discussed in this review.

Comparative Study of Slow Infusion versus Bolus Doses of Albumin and Furosemide Infusion to Mobilize Refractory Ascites in Decompensated Chronic Liver Disease.

BACKGROUND: Combined use of furosemide with albumin is an approved therapy to overcome diuretic resistance in treatment of ascites in decompensated chronic liver disease. Bolus dosing of diuretics has its own limitations due to pre-existing hypotension, post diuretic sodium retention and braking phenomenon. Slow albumin and furosemide Infusion has been shown to mobilize large ascites with improved diuresis and hemodynamic stability in decompensated chronic liver disease. This study was undertaken to compare efficacy and safety of infusion therapy vs bolus therapy in term the management of refractory ascites. METHODS: Decompensated chronic liver disease patients with refractory ascites were randomly assigned into two groups of 15 each - Bolus therapy (intravenous albumin and furosemide as boluses) and Infusion therapy (furosemide infusion at 2mg/hour and albumin at 2g/hour for three days). Diuresis, natriuresis, change in abdominal girth and body weight, and hemodynamic stability (change in SBP) were compared between the two groups. RESULTS: Infusion therapy, as compared to bolus therapy, showed a significantly better diuresis (mean urinary output increment 483ml vs 243ml, p <0.001), natriuresis (mean urinary sodium excretion increment 35.2 mEq/L vs 16.6 mEq/L, p = 0.004),decrease in abdominal circumference (6.1cm vs 3.0cm, p<0.001) and decrease in body weight (5.53 Kg vs 2.86 Kg, p < 0.001). The complications of renal impairment were also lower in the Infusion group. CONCLUSION: Infusion of furosemide and albumin is a potential safer and effective therapeutic option in the management of refractory ascites with better natriuresis, higher urine output, and higher decrement in abdominal circumference and body weight, and lesser side effects.