Early detection of HCC in patients with cirrhosis using AI; a Systematic Review.

Introduction: Hepatocellular carcinoma constitutes for approximately 75% of primary cancers of liver. Around 80- 90% of patients with HCC have cirrhosis at the time of diagnosis. Use of AI has recently gained significance in the field of hepatology, especially for the detection of HCC, owing to its increasing incidence and specific radiological features which have been established for its diagnostic criteria. Objectives: A systematic review was performed to evaluate the current literature for early diagnosis of hepatocellular carcinoma in cirrhotic patients. METHODS: Systematic review was conducted using PRISMA guidelines and the relevant studies were narrated in detail with assessment of quality for each paper. RESULTS: This systematic review displays the significance of AI in early detection and prognosis of HCC with the pressing need for further exploration in this field. CONCLUSIONS: AI can have a significant role in early diagnosis of HCC in cirrhotic patients.

Operating room black box: GIMMICK or a patient safety tool?

The Operating Room Black Box (ORBB) is a relatively recent technology that provides a comprehensive solution for assessing technical and non-technical skills of the operating team. Originating from aviation, the ORBB enables real-time observation and continuous recording of intraoperative events allowing for an in-depth analysis of efficiency, safety, and adverse events. Its dual role as a teaching tool enhances transparency and patient safety in surgical training. In comparison to traditional methods, like checklists that have limitations, the ORBB offers a holistic understanding of clinical and non-clinical performances that are responsible for intraoperative patient outcomes. It facilitates systematic observation without additional personnel, allowing for review of numerous surgical cases. This review highlights the potential benefits of the ORBB in enhancing patient safety, its role as a surgical training tool, and addresses barriers especially in resource-constrained settings. It signifies a transformative step towards global surgical practices, emphasizing transparency and improved surgical outcomes.

A Journey of Innovation: 40 years of Pioneering Medical Education at the Aga Khan University Medical College in Karachi, Pakistan.

This article presents an overview of Aga Khan University's (AKU) pioneering medical education initiatives over the past 40 years, exploring its impact on healthcare in the region and its commitment to advancing medical education and research in the developing world. Established in 1983 as the first private university in Pakistan, AKU has evolved into a global institution with a focus on improving healthcare standards and addressing healthcare needs in the developing world. The article also discusses the undergraduate and postgraduate medical education programs at AKU Medical College, Pakistan, highlighting their unique features and pioneering approaches to medical education. The institution's journey highlights its ability to adapt to the evolving healthcare landscape while maintaining a focus on quality and excellence, offering a model for other institutions striving to meet healthcare needs in low- and middle-income countries.

Aczel-Alsina T-norm based group decision-making technique for the evaluation of electric cars using generalized orthopair fuzzy aggregation information with unknown weights.

Data management and finding precise outcomes from large amounts of information are among the biggest challenges for scientists. The technique of multi-attribute group decision-making (MAGDM) is a valuable tool for investigating fuzzy data precisely. The key objective of the paper is to redefine the q-rung orthopair (q-RO) fuzzy set (FS) (q-ROFS) in the term of interval-valued and proposed new aggregation operators (AOs) based on the Aczel-Alsina (AA) t-norm (TN) and t-conorm (TCN) operations. The AA operational laws are a generalized form of existing TNs and TCNs and give more reliable results because they can fluctuate in their parametric values. The concept of interval-valued enlarges the space of membership degree (MD) and non-membership degree (NMD) for decision-makers. By taking qth power, the interval-valued q-ROFS (IV-q-ROFS) structure. The IV-q-ROFS can handle the uncertainty and vagueness in data, then interval-valued intuitionistic FS (IV-IFS) and interval-valued Pythagorean FS (PyFS) (IV-PyFS) and provide accurate results. The thought of power AOs (PAOs) makes the relationship between weight vectors and reduces the chances of uncertainty in aggregated results. By taking advantage of PAOs, this article is devoted to introducing the interval-valued q-ROF Aczel-Alsina power-weighted averaging (IV-q-ROFAAPWA) and interval-valued q-ROF Aczel-Alsina power-weighted geometric (IV-q-ROFAAPWG) operators. The fundamental axioms of AOs, idempotency, boundedness, and monotonicity, are also discussed. To illustrate the importance of suggested AOs, the real-life problem of electric car selection was solved by applying the MAGDM method using the proposed IV-q-ROFAAPWA and IV-q-ROFAAPWG operators. The comparison of proposed AOs with currently present AOs is also part of the article. We finally constructed solid conclusions.

Phytochemical profile, nutritional composition of pomegranate peel and peel extract as a potential source of nutraceutical: A comprehensive review.

The current study focuses on Punica granatum L. (pomegranate) peel and peel extract and their use as functional foods, food additives, or physiologically active constituents in nutraceutical formulations. The pomegranate peel extract is a good source of bioactive substances needed for the biological activity of the fruit, including phenolic acids, minerals, flavonoids (anthocyanins), and hydrolyzable tannins (gallic acid). The macromolecules found in pomegranate peel and peel extract have been recommended as substitutes for synthetic nutraceuticals, food additives, and chemo-preventive agents because of their well-known ethno-medical significance and chemical properties. Moreover, considering the promises for both their health-promoting activities and chemical properties, the dietary and nutraceutical significance of pomegranate peel and pomegranate peel extract appears to be underestimated. The present review article details their nutritional composition, phytochemical profile, food applications, nutraceutical action, and health benefits.

Norfloxacin derivatives as DNA gyrase and urease inhibitors: synthesis, biological evaluation and molecular docking.

Background: DNA gyrase and urease enzymes are important targets for the treatment of gastroenteritis, appendicitis, tuberculosis, urinary tract infections and Crohn's disease. Materials & methods: Esterification of norfloxacin was performed to enhance DNA gyrase and urease enzyme inhibition potential. Structure elucidation and chemical characterization were done through spectral (1H NMR, Fourier transform IR, 13C NMR) and carbon, hydrogen, nitrogen and sulfur analysis along with molecular docking. Results & conclusion: The majority of derivatives exhibited significant results but the 3e derivative showed maximum bactericidal, DPPH scavenging (96%), DNA gyrase and urease enzyme inhibitory activity with IC50 of 0.15 ± 0.24 and 1.14 ± 0.11 µM respectively which was further supported by molecular docking studies. So, the active derivatives can serve as a lead compound for the treatment of various pathological conditions.

Exploring the 'January effect' at a university hospital in Pakistan: a retrospective cohort study investigating the impact of trainee turnover on patient care quality outcomes.

OBJECTIVE: There are reports of a potential rise in a teaching hospital's morbidity and mortality rates during the trainee turnover period, i.e., with the induction of new residents and house staffs, and the changeover of clinical teams. The published literature displays mixed reports on this topic with lack of reproducible observations. The current study was conducted to explore existence of any such phenomenon (January effect) in Pakistan. METHODS: This retrospective cohort study was conducted at Aga Khan University Hospital, Karachi, Pakistan. Five-year (2013-2018) record of all the patients in all age groups related to these outcomes was retrieved and recorded in specifically designed questionnaire. Different outcome measures were used as indicators of patient care and change in these outcomes at the time of new induction was related to possible January effect. RESULTS: During the five-year study period, more than 1100 new trainees were inducted into the post graduate medical education program (average of 237 per year) with more than 22,000 inpatient admissions (average of 45,469 per year). Some patterns were observed in frequencies of surgical site infections, medication errors, sentinel events, patient complaints, and adverse drug reactions. However, these were not consistently reproducible and could not be directly attributed to the trainee turnover. All other indicators did not show any pattern and were considered inconclusive. No effect of overlap was observed. CONCLUSIONS: Inconsistency in the patient care quality indicators do not favor existence of January effect in our study. Further research is recommended to establish our results.

Noble Gas Functional Defect with Unusual Relaxation Pattern in Solids.

The conventional understanding has always been that noble gases are chemically inert and do not affect materials properties. This belief has led to their use as a standard reference in various experimental applications through noble gas implantation. However, in our research, using first-principles calculations, we delve into the effects of noble gas defects on the properties of several functional oxides, thereby questioning this long-held assumption. We provide evidence that noble gases can indeed serve as functional defects. They have the potential to decentralize the localized defect states and prompt a shift of electrons from the localized state to the conduction band. Our investigation unveils that noble gas defects can indeed significantly alter the material properties. Thus, we underscore the importance of factoring in such defects when assessing material properties.

Disparities in patient-resident physician communication and counseling: A multi-perspective exploratory qualitative study.

Effective communication between physicians and patients plays an integral role in clinical care. Gaps in a physician's ability to ensure effective communication, especially with patients from diverse backgrounds, are known causes of medical errors. This study explores the potential biases and disparities in patient-resident communication, which may influence a patient's quality of care. This exploratory qualitative study was conducted at the largest academic medical center in Pakistan. Purposive sampling was used to approach participants from surgery, medicine, obstetrics and gynecology, pediatrics and family medicine. Faculty, fellows and residents working in these departments and medical students in their fourth and fifth years of undergraduate education with prior experience of at least one month in these specialties during their clinical rotations were included. Focus group discussions (FGDs) lasting 45-60 minutes were conducted with each cohort of healthcare professionals separately, using a semi-structured interview guide. Sixty participants (19 males and 41 females, mean age: 32.9, SD: 10.9) took part in the study. Thematic analysis revealed five major themes. Four themes focused on residents' biases and patient disparities hindering patient-resident communication: (1) patient-resident gender discordance (2) ethnicity and language barriers, (3) differing social class of the patient, and (4) challenging patient-resident interactions (patients resistant to treatment, exceedingly inquisitive and those with multiple attendants, etc.). The fifth theme identified the need for a communication skills curriculum in postgraduate medical education. Opposite gender and discordant socioeconomic/cultural backgrounds of patients pose a challenge to effective patient-physician communication. Self-identification and awareness of residents' biases when interacting with patients can ensure their active elimination and improve their communication skills. Integrating these components in a standardized curriculum within postgraduate programs can enable resident-physicians to provide the same level of care and communicate more efficiently with patients of all backgrounds.

Portal vein thrombosis in patients with hepatocellular carcinoma and early cirrhosis-prevalence and risk factors.

Introduction: Hepatocellular carcinoma (HCC) is frequently associated with portal vein thrombosis (PVT) with prevalence ranging from 25% to 50%. PVT is associated with poor prognosis, limiting the available therapeutic options for these patients. Our objective was to determine the prevalence and risk factors for PVT in patients with HCC. Method: A retrospective analysis was performed on the prospectively collected data from January 2018 to March 2020. All patients with HCC discussed in our weekly multidisciplinary liver clinic were reviewed. Multivariate analysis was done to identify the independent risk factors for PVT in HCC patients. A p-value of <0.05 was considered significant. Result: Of 316 patients, the prevalence of PVT was 31% (n = 98). Larger tumour size (p < 0.001), raised Alpha Fetoprotein (AFP) level (p = 0.036) and higher Child-Pugh class (p = 0.008) were significantly associated with PVT. In 216 patients with preserved liver function (Child-Pugh class A), PVT was seen in 53 (24.5%) patients. Large tumour size (p < 0.001) and higher AFP levels (p = 0.021) were independent risk factors. Conclusion: Overall prevalence of PVT in HCC was 31% whereas 24.5% in patients with early cirrhosis (Child-Pugh class A). We identified various risk factors associated with PVT in our local population, highlighting the importance of early and regular screening of cirrhotic patients including Child-Pugh class A.

Spontaneous off-stoichiometry as the knob to control the dielectric properties of gapped metals.

Using first-principles calculations and La3Te4 as an example of an n-type gapped metal, we demonstrate that gapped metals can develop spontaneous defect formation resulting in off-stoichiometric compounds. Importantly, these compounds have different free carrier concentrations and can be realized by optimizing the synthesis conditions. The ability to tune the free carrier concentration allows the tailoring of the intraband and interband transitions, thus controlling the optoelectronic properties of materials in general. Specifically, by realizing different off-stoichiometric La3-xTe4 compounds, it is possible to reach specific crossings of the real part of the dielectric function with the zero line, reduce the plasma frequency contribution to the absorption spectra, or, more generally, induce metal-to-insulator transition. This is particularly important in the context of optoelectronic, plasmonic, and epsilon-near-zero materials, as it enables materials design with a target functionality. While this work is limited to the specific gapped metal, we demonstrate that the fundamental physics is transferable to other gapped metals and can be generally used to design a wide class of new optoelectronic/plasmonic materials.

Need For A National Cancer Registry In Pakistan: Challenges And Way Forward.

The incidence of cancer is rising globally at a remarkable rate. According to the global cancer Observatory, the total number of cases in Pakistan were 178,388 in 2020; and these figures were provided by the Punjab Cancer Registry which represents the population of Lahore and some parts of central Punjab. Considering the overall 220 million population, these figures are severe underestimation of the true cancer burden in Pakistan. Unfortunately, several attempts at establishing a national cancer registry in the country have failed in the past. Resource limitations, including funds, manpower and infrastructure, and the lack of interest on the part of the governments are behind the failure of the establishment of a national cancer database. There is a dire need for establishing a national cancer registry to understand the actual burden of disease, and to implement a national action plan for cancer prevention, and management strategies to control the growing epidemic.

Evaluation of quality of life of gastrointestinal cancer patients presenting to a tertiary care hospital in Pakistan.

Introduction: Quality of life (QOL) appraisal is a meaningful method of outcomes assessment in patients with gastrointestinal (GI) cancer. The aim of our study was to evaluate QOL of patients suffering from GI cancer, who underwent treatment at Aga Khan University Hospital (AKUH), Karachi, Pakistan. Methods: It was a cross-sectional study. A total of 158 adults from December 2020 to May 2021 were included in the study. The EORTC QLQ-C30, validated in Urdu (Pakistan) version, was used to assess the QOL of the participants. Mean QOL scores were calculated and compared with threshold of clinical importance (TCI). Multivariate analysis was done to analyse the correlation between independent factors and QOL scores. A p value of <0.05 was considered as significant. Results: Mean age of the study participants was 54.5 ± 13 years. Majority were male, married and living in combined family system. Most common GI cancer was colorectal (61%) followed by stomach (33.5%); and the most frequent stage at presentation was stage III (40%). Global QOL score was found to be 65.48 ± 1.78. Among functioning scales, role functioning, social functioning, emotional functioning and cognitive functioning were found to be above TCI, whereas physical functioning was found to be below TCI. Among symptom scores, fatigue, pain, dyspnoea, insomnia, appetite loss, constipation and diarrhoea were found to be below TCI, whereas nausea/vomiting and financial impact were found to be above TCI. Multivariate analysis revealed that history of surgery had a positive association (p < 0.001), while being on treatment (p = 0.001) and having a stoma (p = 0.038) had a negative impact on global QOL. Conclusion: This is the first study to evaluate the QOL scores in GI cancer patients in Pakistan. There is a need to identify the reasons for low physical functioning score and explore means to mitigate symptoms scores above TCI in our population.

Leveraging the vantage point - exploring nurses' perception of residents' communication skills: a mixed-methods study.

INTRODUCTION: Effective communication is key to a successful patient-doctor interaction and improved healthcare outcomes. However, communication skills training in residency is often subpar, leading to inadequate patient-physician communication. There is a dearth of studies exploring the observations of nurses - key members of healthcare teams with a special vantage point to observe the impact of residents' communication with patients. Thus, we aimed to gauge the perceptions of nurses regarding residents' communication skills expertise. METHODS: This study employed a sequential mixed-methods design, and was conducted at an academic medical center in South Asia. Quantitative data was collected via a REDCap survey using a structured validated questionnaire. Ordinal logistic regression was applied. For qualitative data, In-depth interviews were conducted with nurses using a semi-structured interview guide. RESULTS: A total of 193 survey responses were obtained from nurses hailing from various specialties including Family Medicine (n = 16), Surgery (n = 27), Internal Medicine (n = 22), Pediatrics (n = 27), and Obstetrics/Gynecology (n = 93). Nurses rated long working hours, infrastructural deficits, and human failings as the main barriers to effective patient-resident communication. Residents working in in-patient settings were more likely to have inadequate communication skills (P-value = 0.160). Qualitative data analysis of nine in-depth interviews revealed two major themes: existing status-quo of residents' communication skills (including deficient verbal and non-verbal communication, bias in patient counselling and challenging patients) and recommendations for improving patient-resident communication. CONCLUSION: The findings from this study highlight significant gaps in patient-resident communication from the perception of nurses and identify the need for creating a holistic curriculum for residents to improve patient-physician interaction.

Fermi-Level Instability as a Way to Tailor the Properties of La3Te4.

Traditionally, the formation of off-stoichiometric compounds is believed to be the growth effect rather than the intrinsic tendency of the system. However, here, using the example of La3Te4, we demonstrate that in n-type gapped metals having a large internal gap between principal band edges and the Fermi level inside of the principal conduction band, Fermi-level instability can develop, resulting in a decrease in the formation energy for acceptor defects. Specifically, La vacancies in La3Te4 form spontaneously to produce the acceptor states and remove a fraction of free carriers from the principal conduction band via electron-hole recombination. Such a unique self-doping mechanism allows stabilization of a range of off-stoichiometric La3-xTe4 compounds, which have different electronic properties. Moreover, we thus show how controlling synthesis conditions can be used as a knob to reach the target functionality, including the controllable metal-to-insulator transition.

Surgical and Oncological Outcomes of Hepatic Resection for Hepatocellular Carcinoma: Report from a Low Volume Centre in a Developing Country.

OBJECTIVE: To review the surgical and oncological outcomes of patients who underwent hepatic resection for hepatocellular carcinoma (HCC). STUDY DESIGN: Cohort study. PLACE AND DURATION OF STUDY: Department of Surgery of the Aga Khan University Hospital Karachi, from 2008 to 2019. METHODOLOGY: Consecutive patients who underwent hepatic resection for HCC at the Hospital were included. The data were collected and analysed on aspects including demographics, liver function status, tumour characteristics, perioperative management, and surgical and oncological outcomes. Survival analyses were performed using the Kaplan-Meier method, and log-rank test was applied to determine the influence of variables on overall and disease-free survival. RESULTS: A total of 59 patients underwent hepatic resection for HCC during the study period including 38(64%) males. The majority of the patients had a single lesion (88%), unilobar disease (95%), underlying cirrhosis (75%) and BCLC stage B (73%). Major hepatic resection was performed in 27(46%) patients. The mean duration of surgery was 288+101 minutes and the mean estimated blood loss was 986+637 mls. Postoperative complications developed in 22(37%) patients including surgical complications in 11(19%), liver decompensation in 4(7%) and systemic complications in 9(15%) patients. The overall 30-day mortality was 7%. With a mean follow-up of 2.8 years, disease recurrence was documented in 25(42%) patients and the median overall survival was 45 months. CONCLUSION: Hepatic resection for HCC is an effective treatment option in this setup. Despite low volumes, surgical and oncological outcomes of hepatic resection for HCC were comparable to the international standards. KEY WORDS: Hepatocellular carcinoma, Liver resection, Cirrhosis.

Fast dissolving oral films: An approach to co-load and deliver the atorvastatin and ezetimibe for better therapeutic response.

Atherosclerotic patients suffering with acute coronary disease are lying at high risk. This life-threatening problem can be curtailed by using statins e.g., ezetimibe (EZT), atorvastatin calcium (ATC). In this study, co-loaded Fast Dissolving oral films (FDOFs), of ATC-EZT with HPMC E5 prepared by solvent evaporation method. Prepared FDOFs were evaluated for physicochemical, thermal and mechanical properties. In-vivo animal studies were performed on albino rats against diet induced hyperlipidemia. Prepared FDOFs have rapid DT; 27sec, TDT >2min and in-vitro drug release 97% in a min. In DSC, FTIR and XRD analysis, prepared films were chemically compatible and no chemical interaction of drugs and excipient was found. In kinetic modeling, it was observed their EZT exhibited lowest R2 value for zero order kinetic and best fit model was first order kinetic (n, 0.9823). The korsmeyer peppas model films (n, 0.016) indicate fickian type drug diffusion. The groups treated with marketed suspension of drug and FODPs were compared with normal group and high fats diet group. Study reviled that combination FDOPs of both ATC/EZT significantly reduce hyperlipemia as compared to high fat diet group. It can be concluded that ATC and EZT encapsulated in FODFs provide instant drug release and better therapeutic outcomes.

Formulation of Modified-Release Bilayer Tablets of Atorvastatin and Ezetimibe: An In-Vitro and In-Vivo Analysis.

The objective of this work was to formulate co-loaded bilayer tablets containing ezetimibe (EZB) and atorvastatin (ATC). ATC loaded in the immediate-release (IR) layer is an HMG CoA reductase inhibitor, while EZB, added in the sustained-release (SR) layer, is a lipid-lowering agent. This study was conducted to evaluate the effects of polymer on the formulation and characterization of bilayer tablets, as well as the therapeutic impact of the concurrent use of both drugs having a sequential release pattern. To obtain the optimized results, four different formulations with variable compositions were developed and evaluated for different parameters. The drug release studies were carried out using a type II dissolution apparatus, using phosphate buffer solution (PBS) of 1.2 pH for IR of EZB for an initial 2 h, followed by 24 h studies for ATC in PBS 6.8 pH. The IR layer showed rapid drug release (96%) in 2 h, while 80% of the ATC was released in 24 h from the SR layer. Locally obtained, 6-week-old female albino rats were selected for in vivo studies. Both preventive and curative models were applied to check the effects of the drug combination on the lipid profile, atherosclerosis and physiology of different organs. Studies have shown that the administration of both drugs with different release patterns has a better therapeutic effect (p < 0.05), both in preventing and in curing hyperlipidemia. Conclusively, through the sequential release of ATC and EZB, a better therapeutic response could be obtained.

Prospective comparison of single encounter versus distributed laparoscopic training in novice learners: A controlled trial.

BACKGROUND: The traditional model of teaching surgical skills on "real" patients using graded responsibility is being seriously questioned, and there is a paradigm shift toward exploiting simulators. There is a lack of clarity on the impact of using simulation as a teaching strategy in novice learners. The purpose of our study was to determine if the number and duration of training sessions influence the acquisition and retention of laparoscopic skills in naïve learners. There are some data to suggest that distributed training programs might have better outcomes, but the results are inconclusive. We designed a controlled trial at Aga Khan University, Karachi, with the hypothesis that students trained using the distributed method may have enhanced learning outcomes. MATERIALS AND METHODS: 100 medical students were assigned in a 1:1 ratio to one of two groups. Group A underwent a single orientation and supervised practice session of 3 h duration. Group B underwent distributed teaching with three learning sessions of 1 h each spread over 3 consecutive weeks. Participant scores were analyzed before and after the intervention and at 3- and 6-month intervals using repeat measures of ANOVA. RESULTS: Pretest and immediate posttest scores were comparable between the two groups. The 3-month interval test showed significantly higher scores in Group B (difference = -2.90, P < 0.001). The 6-month interval test showed no differences in scores between the two groups (P = 0.178). CONCLUSIONS: Distributed teaching resulted in significantly enhanced scores at 3-month assessment. However, similar scores at 6 months suggest the need for repeated intervention.

Paraganglioma of common bile duct: A case report.

Paragangliomas are rare tumours derived from the neural crest cells. Most common site for these tumours is the adrenal medulla, where they are called as pheochromocytomas. Biliary system is an extremely uncommon site for extra-adrenal paraganglioma. We report the case of a 55 year old female who presented with one-month history of jaundice and right upper quadrant discomfort. Imaging showed a well-defined rounded mass at porta hepatis with arterial enhancement causing compression over the proximal common bile duct, resulting in moderate intrahepatic biliary dilatation. The patient underwent radical excision of common bile duct and roux-en-y hepaticojejunostomy. Final histopathology confirmed paraganglioma. Approximately 10% of patients may present with extra-adrenal disease, but biliary paraganglioma are extremely rare. Only few cases have been reported in literature and the management usually involves the surgical excision. Being a rare disease, a high index of suspicion is important for diagnosis of paraganglioma at such an uncommon location.