Frailty in end-stage liver disease: Understanding pathophysiology, tools for assessment, and strategies for management.

Frailty and sarcopenia are frequently observed in patients with end-stage liver disease. Frailty is a complex condition that arises from deteriorations across various physiological systems, including the musculoskeletal, cardiovascular, and immune systems, resulting in a reduced ability of the body to withstand stressors. This condition is associated with declined resilience and increased vulnerability to negative outcomes, including disability, hospitalization, and mortality. In cirrhotic patients, frailty is influenced by multiple factors, such as hyperammonemia, hormonal imbalance, malnutrition, ascites, hepatic encephalopathy, and alcohol intake. Assessing frailty is crucial in predicting morbidity and mortality in cirrhotic patients. It can aid in making critical decisions regarding patients' eligibility for critical care and transplantation. This, in turn, can guide the development of an individualized treatment plan for each patient with cirrhosis, with a focus on prioritizing exercise, proper nutrition, and appropriate treatment of hepatic complications as the primary lines of treatment. In this review, we aim to explore the topic of frailty in liver diseases, with a particular emphasis on pathophysiology, clinical assessment, and discuss strategies for preventing frailty through effective treatment of hepatic complications. Furthermore, we explore novel assessment and management strategies that have emerged in recent years, including the use of wearable technology and telemedicine.

Radiological-histopathological discordance in patients transplanted for HCC and its impact on post-transplant outcomes.

BACKGROUND AND AIMS: Contrast-enhanced cross-sectional imaging is the cornerstone in the diagnosis, staging, and management of HCC, including eligibility for liver transplantation (LT). Radiological-histopathological discordance may lead to improper staging and may impact patient outcomes. We aimed to assess the radiological-histopathological discordance at the time of LT in HCC patients and its impact on the post-LT outcomes. METHODS: We analyzed further the effect of 6-month waiting policy on the discordance. Using United Network for Organ Sharing-Organ Procurement and Transplantation Network (UNOS-OPTN) database, we examined the discordance between pre-LT imaging and explant histopathology for all adult HCC patients who received liver transplants from deceased donors between April 2012 and December 2017. Kaplan-Meier methods and Cox regression analyses were used to evaluate the impact of discordance on 3-year HCC recurrence and mortality. RESULTS: Of 6842 patients included in the study, 66.7% were within Milan criteria on both imaging and explant histopathology, and 33.3% were within the Milan based on imaging but extended beyond Milan on explant histopathology. Male gender, increasing numbers of tumors, bilobar distribution, larger tumor size, and increasing AFP are associated with increased discordance. Post-LT HCC recurrence and death were significantly higher in patients who were discordant, with histopathology beyond Milan (adj HR 1.86, 95% CI 1.32-2.63 for mortality and 1.32, 95% CI 1.03-1.70 for recurrence). Graft allocation policy with 6-month waiting time led to increased discordance (OR 1.19, CI 1.01-1.41), although it did not impact post-LT outcome. CONCLUSION: Current practice for staging of HCC based on radiological imaging features alone results in underestimation of HCC burden in one out of three patients with HCC. This discordance is associated with a higher risk of post-LT HCC recurrence and mortality. These patients will need enhanced surveillance to optimize patient selection and aggressive LRT to reduce post-LT recurrence and increase survival.

The effect of a thumb web spacer splint on hand function in children with hemiplegic cerebral palsy.

Objective: Many children with hemiplegic cerebral palsy (HCP) cannot maintain thumb abduction and experience obstruction caused by the thumb remaining in the palm. A web spacer splint maintains the thumb web space and opposition of the thumb for a more functional position. The aim of this study was to analyze the impact of a thumb web spacer as a functional splint on hand function in children with hemiplegic cerebral palsy. Methods: Thirty children with hemiplegic cerebral palsy (ages 4-7 years) were randomly divided into two groups (a control group and a study group). The treatment program for the control group was administered for 45 min three times/week for 8 successive weeks and the study group underwent the identical treatment regimen as the control group, as well as wearing a web spacer splint during the treatment program. Thereafter, the Peabody Developmental Motor Scale (PDMS-2) was used to assess hand function. Results: Post-treatment values in the study group demonstrated a substantial improvement in grasping and visual motor integration in the PDMS-2 when compared to the control group. Therefore, there was a significant improvement in total fine motor quotient when compared post-treatment (86.93 ± 8.94, 145.73 ± 15.04) in the control and study groups, respectively (p > 0.05). Conclusion: A web spacer splint can be a viable tool for improving hand function in children with HCP.

Current Status of Biomarkers and Molecular Diagnostic Tools for Rejection in Liver Transplantation: Light at the End of the Tunnel?

Strategies to minimize immune-suppressive medications after liver transplantation are limited by allograft rejection. Biopsy of liver is the current standard of care in diagnosing rejection. However, it adds to physical and economic burden to the patient and has diagnostic limitations. In this review, we aim to highlight the different biomarkers to predict and diagnose acute rejection. We also aim to explore recent advances in molecular diagnostics to improve the diagnostic yield of liver biopsies.

An Observational Study of Fixed Drug Eruption in A Tertiary Care Hospital in Bangladesh.

Fixed drug eruption (FDE) is a distinctive pattern of cutaneous adverse drug reaction. Characteristically the eruption recurs at the same site on re exposure to the offending agent. Aim of this study was to evaluate and identification of the various offending drugs causing FDE which may help the physician to limit the associate complication regarding the drug. This observational cross sectional study was conducted from 1st June 2021 to 31st May 2022 in the department of Dermatology & Venereology of Mymensingh Medical College Hospital after taking approval from institutional ethical committee. A detailed history with clinical evaluation were done for all patients with FDE and thereby recorded in a pre designed proforma. Analysis of data was done using Microsoft Excel 2010 Spread sheet. Out of 65 cases 36(55.38%) were male and 29(44.6%) were female. Majority of cases were found in the age group of 31 to 40 years. The most common group of drug causing FDE was NSAID (52.31%) followed by antimicrobials (44.61%) and anti epileptics (3.07%). Ibuprofen (20.0%) was the most common offending drug followed by doxycycline (18.46%), diclofenac and fluconazole (13.84%), naproxen (9.23%), ciprofloxacin (7.69%), paracetamol (6.15%), metronidazole (4.61%), carbamazepine (3.07%) and aspirin (3.07%) respectively. Extremities (43.07%) were the most frequently involved site followed by trunk (29.23%) and face (10.77%). Generalized FDE found in 16.92% cases. Although FDE are very common the offending drugs show some regional variation as a result of changing trends of pharmacotherapy.

Sinapic acid restores blood parameters, serum antioxidants, and liver and kidney functions in obesity.

Obesity is an additional body fat that causes a harmful effect on human health while sinapic acid (SA) is a phyto-constituent presents in spices, citrus, berry fruits, and vegetables. This study evaluates SA to amend blood parameters, serum glucose, proteins, lipids, and antioxidants, and liver and kidney functions in obese rats. Thirty male albino rats were divided into 2 groups (normal and obese rats). The normal, non-obese rats subdivided into 2 subgroups; Control and SA (40 mg/kg) subgroup: daily oral intake of 1 ml saline and 40 mg/kg SA, respectively once a day. The obese rats subdivided also into 3 subgroups; Obese, Obese + SA (20 mg/kg), and Obese + SA (40 mg/kg)-treated groups which received no treatment, 20 mg/kg SA, and 40 mg/kg SA, respectively once a day. All treatments were orally administrated for 1 month. The results showed that obesity caused an increase in body and organ weight, serum total cholesterol, triglycerides, low density lipoproteins, malondialdehyde, nitric oxide, glucose, bilirubin and blood urea nitrogen while decrease serum superoxide dismutase, glutathione peroxidase, glutathione, glutathione reductase, glutathione-S-transferase, hemoglobin, hematocrite, red blood cells, white blood cells, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, urea, creatinine, and uric acid compared to control group. Obesity caused disappearance of prothrombin and fibrinogen proteins and damages to liver and kidney tissues. The oral administration with SA daily for 1 month in obese rats returned all these parameters to the control values where the higher dose of SA was more effective than the lower dose. In conclusion, SA restores body and organ weight, blood parameters, serum glucose, proteins, lipids, antioxidants, and liver and kidney functions in obesity.

Implementing a digital human resources management tool in the government health sector in Bangladesh: a policy content analysis.

INTRODUCTION: In Bangladesh, to address the challenges of ensuring adequate human resources for health (HRH), the government began implementing a digital tool for HRH management in 2017. However, evidence suggests institutionalizing such tools in low-and-middle-income countries is impeded by policy aspects like implementation strategy and poor regulatory framework. Therefore, we aimed to explore factors in the current policy landscape that might facilitate and challenge the implementation of the tool in Bangladesh. METHODS: We conducted a review of policies related to ICT implementation and human resources management in the health sector in Bangladesh using qualitative content analysis method. Ten policies have been identified, and extensive reading was done to ascertain common themes and patterns. A document analysis matrix was developed to synthesize and help interpret the findings. RESULTS: Regarding facilitators, strong upstream level commitments were reflected in the content of policies in terms of setting out specific objectives, targets, timelines, and budget allocation. However, the lack of explicit monitoring strategy and extent of stakeholders' engagement was not well-defined, ultimately creating chances for impeding downstream implementation. In addition, effective coordination among stakeholders and different HRH and ICT policies could be strengthened. DISCUSSION: Findings support the current discourse that national commitment plays a vital role in the integration of ICTs in health services. However, well-defined monitoring strategy and inter-ministry and intra-ministry policy coordination are crucial.

Feasibility, user experiences, and preliminary effect of Conversation Cards for Adolescents© on collaborative goal-setting and behavior change: protocol for a pilot randomized controlled trial.

BACKGROUND: Adolescents and providers can benefit from practical tools targeting lifestyle modification for obesity prevention and management. We created Conversation Cards for Adolescents© (CCAs), a patient-centered communication and behavior change tool for adolescents and providers to use in clinical practice. The purpose of our study is to (i) assess the feasibility of CCAs in a real-world, practice setting to inform full-scale trial procedures, (ii) assess user experiences of CCAs, and (iii) determine the preliminary effect of CCAs on changing behavioral and affective-cognitive outcomes among adolescents. METHODS: Starting in early 2019, this prospective study is a nested mixed-methods, theory-driven, and pragmatic pilot randomized controlled trial with a goal to enroll 50 adolescents (13-17 years old) and 9 physicians practicing at the Northeast Community Health Centre in Edmonton, Alberta, Canada. Adolescents will collaboratively set one S.M.A.R.T. (specific, measurable, attainable, realistic, timely) goal with their physician to implement over a 3-week period; however, only those randomized to the experimental group will use CCAs to inform their goal. Outcome assessments at baseline and follow-up (3 weeks post-baseline) will include behavioral, affective-cognitive, and process-related outcomes. DISCUSSION: In examining the feasibility, user experiences, and preliminary effect of CCAs, our study will add contributions to the obesity literature on lifestyle modifications among adolescents in a real-world, practice setting as well as inform the scalability of our approach for a full-scale effectiveness randomized controlled trial on behavior change. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03821896.

The reproducibility of the novel utilization of five-dimensional ultrasound and power Doppler in the prediction of endometrial receptivity in intracytoplasmic sperm-injected women: a pilot prospective clinical study.

OBJECTIVE: The ultimate goal of this study is to reassess the five-dimensional implantation markers and pregnancy predictors on the day of human chorionic gonadotropin injection in the intracytoplasmic sperm injection and embryo transfer programs. DESIGN: A pilot prospective clinical trial. SETTING: The Assisted Reproductive Technology Unit of Ain Shams Maternity Teaching Hospital during the period from April 2014 to December 2017. PATIENTS AND METHODS: The study was conducted on 400 women undergoing intracytoplasmic sperm injection (ICSI). Those women were not older than 40 years, with normal uterine cavity and with no previous uterine scars. INTERVENTION: The ovarian stimulation protocol, used in this study for all patients, was the long protocol, before ovarian stimulation therapy, patients were instructed to use oral contraceptive pills from day 2 starting in the preceding cycle, then the standard regimen. On the day of hCG administration, 5D transvaginal ultrasound measurements were performed by the same observer after the patients had emptied their bladders. Measurements included endometrial volume and 3D power Doppler parameters, endometrial vascularization index, flow index, and vascularization flow index. RESULTS: The present study shows that endometrial volume ≥ 5 in the prediction of endometrial receptivity in ICSI patients had good sensitivity and low specificity in a group application; in an individual application it had good predictive negative value and bad predictive positive value. So it could be used as a good test to exclude success. Overall pregnancy rate was 40.5%; endometrial volume, flow index, vascularization index, and vascularization flow index were significantly lower in the nonpregnant group than those of the pregnant group. The area under curve in the receiver operating characteristic for three-dimensional ultrasound and power Doppler angiography parameters was statistically significant, but their values were suggestive but not conclusive in the prediction of endometrial receptivity in ICSI patients, no cutoff points with good diagnostic characteristics could be obtained. CONCLUSION: Five-dimensional ultrasound and power Doppler angiography is a useful exam to assess the endometrial receptivity in IVF/ICSI and embryo transfer cycles.

Inferior vena cava filter penetration following Whipple surgical procedure causing ureteral injury.

We report a case of an indwelling inferior vena cava filter that penetrated the IVC wall after Whipple's pancreatico-duodenectomy procedure performed in a patient with ampullary carcinoma, resulting in right ureteral injury and obstruction with subsequent hydroureter and hydronephrosis. This was incidentally discovered on a computed tomography scan performed as routine follow up to evaluate the results of the surgery. We retrieved the inferior vena cava filter and placed a nephrostomy catheter to relieve the ureteral obstruction. Our case highlights the importance of careful inferior vena cava manipulation during abdominal surgery in the presence of an inferior vena cava filter, and the option of temporary removal of the filter to be placed again after surgery in order to avoid this complication, unless protection is required against clot migration during the surgical procedure.

Protective effect of Cupressus sempervirens extract against indomethacin-induced gastric ulcer in rats.

Cupressus sempervirens (C. sempervirens) belongs to the family Cupressaceae. It is widspread in Northern Africa, Greece, Turkey, North America, Cyprus and Syria. Cupressuflavone is the major ingredient of the plant leave extract. The aim of the present study was to evaluate the antiulcerogenic activity of the extract of C. sempervirens leaves in gastric ulcer tissues induced by indomethacin. The results of the present study revealed that indomethacin significantly decreased glutathione S-transferase (GST), glutathione peroxidase (GPx), catalase (CAT), reduced glutathione (GSH), glutathione reductase (GR) and superoxide dismutase (SOD) levels, while it increased significantly lipid peroxidation (MDA), nitric oxide (NO) and protein carbonyl (PC) levels in gastric tissue. Furthermore, indomethacin decreased p53 expression, while it increased bcl-2 expression in gastric tissue. Pretreatment with 5%, 10% & 20% of the LD50 of C. sempervirens and cupressuflavone of indomethacin-treated rats restored all the above parameters to approach normal values. C. sempervirens at the highest dose was more effective than the two lower doses. C. sempervirens proved more potent than cupressuflavone. In conclusion, C. sempervirens exerted antiulcerogenic activity and the effect was dose-dependent and related to the cupressuflavone ingredient of the plant leave extract.

Endovascular treatment of acute portal vein thrombosis using ultrasound-accelerated catheter-directed thrombolysis.

We report a case of extensive acute portal vein thrombosis (PVT) presenting with severe diffuse abdominal pain and impending small bowel infarction. The patient was successfully treated with ultrasound-accelerated catheter-directed thrombolysis (EKOS endowave system; Covidien, Mansfield, Massachusetts), which resulted in prompt recanalization of his portal vein (PV) and its tributaries. The patient eventually had ischemic stricture that necessitated bowel resection. However, we believe that our technique was successful in rapidly restoring the patency of the PV and its tributaries, and therefore, avoiding a life-threatening complication of more extensive bowel infarction. To our knowledge, the use of ultrasound-accelerated thrombolysis in treatment of PVT has not been previously described in the literature.

Type 2 cGMP-dependent protein kinase regulates homeostasis by blocking c-Jun N-terminal kinase in the colon epithelium.

Analysis of knockout animals indicates that 3',5'cyclic guanosine monophosphate (cGMP) has an important role in gut homeostasis but the signaling mechanism is not known. The goals of this study were to test whether increasing cGMP could affect colon homeostasis and determine the mechanism. We increased cGMP in the gut of Prkg2(+/+) and Prkg2(-/-) mice by treating with the PDE5 inhibitor Vardenafil (IP). Proliferation, differentiation and apoptosis in the colon mucosa were then quantitated. Vardenafil (Vard) treatment increased cGMP in colon mucosa of all mice, but reduced proliferation and apoptosis, and increased differentiation only in Prkg2(+/+) mice. Vard and cGMP treatment also increased dual specificity protein phosphatase 10 (DUSP10) expression and reduced phospho-c-Jun N-terminal kinase (JNK) levels in the colon mucosa of Prkg2(+/+) but not Prkg2(-/-) mice. Treatment of Prkg2(-/-) mice with the JNK inhibitor SP600125 reversed the defective homeostasis observed in these animals. Activation of protein kinase G2 (PKG2) in goblet-like LS174T cells increased DUSP10 expression and reduced JNK activity. PKG2 also increased goblet cell-specific MUC2 expression in LS174T cells, and this process was blocked by DUSP10-specific siRNA. The ability of cGMP signaling to inhibit JNK-induced apoptosis in vivo was demonstrated using dextran sodium sulfate (DSS) to stress the colon epithelium. Vard was a potent inhibitor of DSS-induced epithelial apoptosis, and significantly blocked pathological endpoints in this model of experimental colitis. In conclusion, Vard treatment activates cGMP signaling in the colon epithelium. Increased PKG2 activity alters homeostasis by suppressing proliferation and apoptosis while promoting differentiation. The PKG2-dependent mechanism was shown to involve increased DUSP10 and subsequent inhibition of JNK activity.

Novel effect of plant lectins on the inhibition of Streptococcus mutans biofilm formation on saliva-coated surface.

AIMS: Dental caries is caused by the disturbance in oral homeostasis, marked by a notable increase in the population of Streptococcus mutans. Lectins are a group of plant proteins that are capable of recognizing the glycoconjugates present on the bacterial surface. The aim of this study was to evaluate the effect of seven plant lectins on the growth and initial adhesion of S. mutans. METHODS AND RESULTS: Lectins of different carbohydrate specificities were isolated from plant sources by conventional methods of protein purification. The effect on growth of S. mutans was evaluated following CLSI guidelines. None of the lectins used in this study inhibited the bacterial growth and multiplication. The adherence and biofilm formation of bacteria to saliva-coated polystyrene plates was tested in the presence of plant lectins. All the plant lectins tested, inhibited both the adherence and biofilm in a concentration dependent manner. Confocal microscopy and scanning electron microscopy were employed to assess the biofilm formation in the presence of plant lectin (glucose/mannose-specific) at sub-minimal inhibitory concentrations. These evaluations revealed that lectins inhibited the clumping and attachment of S. mutans. CONCLUSIONS: Lectins tested here inhibited initial biofilm formation by S. mutans. Glucose/Mannose-specific lectin altered the adhesion arrangement of the bacteria on the saliva-coated surfaces. SIGNIFICANCE AND IMPACT OF THE STUDY: The plant lectins used in this study may offer a novel strategy to reduce development of dental caries by inhibiting the initial adhesion and subsequent biofilm formation of S. mutans.

Inhibition of protein phosphatase-1 by clavosines A and B. Novel members of the calyculin family of toxins.

Site-directed mutagenesis was used to investigate the mechanism of interaction between the catalytic subunit of human protein phosphatase-1 (PP-1cgamma) and members of the calyculin family of toxins. Clavosines A and B are related to calyculins but are glycosylated with a trimethoxy rhamnose group. We provide experimental evidence implicating Tyr-134 as an important residue in PP-1cgamma that mediates interactions with the calyculins. Mutation of Tyr-134 to Phe, to prevent hydrogen bond formation, resulted in a slight increase in sensitivity of PP-1cgamma to clavosines A and B and calyculin A. In contrast, a Y134A mutant was 10-fold less sensitive to inhibition by all three inhibitors. The greatest effect on inhibition was found by substituting an Asp for Tyr-134 in the phosphatase. Clavosine B inhibited PP-1cgamma Y134D with a 310-fold decrease in potency. Clavosine A and calyculin A were also markedly poorer inhibitors of this mutant. These results suggest that a hydrogen bond between Tyr-134 and the calyculins is unlikely to be essential for inhibitor binding to the phosphatase. The clavosines and calyculin A were tested for their ability to inhibit other mutants of PP-1cgamma (including Ile-133, Val-223, and Cys-291). Our mutagenesis studies provide an experimental basis for assessing models of calyculin binding found in the literature (Lindvall, M. K., Pihko, P. M., and Koskinen, A. M. (1997) J. Biol. Chem. 272, 23312-23316; Gupta, V., Ogawa, A. K., Du, X., Houk, K. N., and Armstrong, R. W. (1997) J. Med. Chem. 40, 3199-3206; Gauss, C. M., Sheppeck, I. J., Nairn, A. C., and Chamberlain, R. (1997) Bioorg. Med. Chem. 5, 1751-1773). A new model for clavosine and calyculin A binding to PP-1c is presented that is consistent with previous structure-function experiments and which accommodates key structural features of the clavosines, including the novel rhamnose moiety.

IgA nephropathy in teaching hospitals of Dhaka.

A light and immunofluorescence microscopic study on renal biopsies were performed on 42 patients. Nephrotic syndrome with accompanying microhematuria and recurrent hematuria (Macroscopic/microscopic) with or without renal failure were the commonest indications for renal biopsy. Primary IgA nephropathy was diagnosed in five cases. Among the IgA nephropathy patients, the commonest light microscopic finding was mesangial proliferative glomerulonephritis. Macroscopic hematuria with proteinuria was the commonest feature. Three of the patients had hypertension at the time of renal biopsy. The age of the patients ranged from 19-38 years with a mean of 26 years. The high frequency of hypertension, degree of proteinuria and associated renal failure in one patient that it is a progressive disease. This preliminary study revealed that IgA nephropathy exists in Bangladesh. Larger samples need to be studied with a view to find out its prevalence and its peculiarities in this part of the world.

Effect of onion extract on immune response in rabbits.

A total of 40 NZW rabbits were selected for this study to see the effect of onion extract on immune response following antigenic challenge. These animals were randomly divided into four groups, each composed of ten rabbits. Group I and II were challenged with typhoid H (TH) antigen and groups III and IV with sheep red blood cells (SRBC). Groups I and III were considered as control and II and IV as treated groups. The latter two groups were treated with onion extract orally. The immunosuppressive effect of onion extract was evaluated by estimating antibody levels by Widal test and hemolysin titer. It was found that mean antibody titers were significantly lower in the treated groups than in controls. The weights of thymus and lymph nodes were higher and of adrenal glands were lower in the control groups than in the treated groups. It appeared from the current study that onion extract has an inhibitory effect on immune response.

Preparation of cupric palmitate membrane, its characterization and evaluation of thermodynamically effective fixed charge density.

Membrane potentials have been measured across parchment-supported cupric palmitate membrane separating various 1:1 electrolytes at concentrations C1 and C2 such that C2 = 10 C1. Membrane potential data have been used to calculate transference number of ions, permselectivity and also to derive the thermodynamically effective fixed charge density which is an important characteristic governing the membrane phenomena by utilizing the generally accepted and most widely used theory of Teorell-Meyer and Sievers as well as the recent theories for membrane potential of Kobatake et al. and Nagasawa et al. based on the principles of nonequilibrium thermodynamics. The values of charge densities derived from different theories were almost the same, confirming thereby the validity of the recently developed theories of membrane potential.

Intestinal parasites in University of Dacca students.

Nine hundred and thirty three students of Dacca University were examined: mean haemoglobin levels were 80.5 per cent for men and 70.0 per cent for women. Five hundred and thirty three (57.3%) of the students had single or multiple intestinal parasitic infections, of which Ascaris lumbricoides (366), Entamoeba histolytica (113) and Trichuris trichiura (99) were the commonest. It is suggested that chronic nutritional deficiencies are compounded by these parasites, leading to low weights, and low haemoglobins.