1.Microbiome-centered therapies for the management of metabolic dysfunction-associated steatotic liver disease
Huma SAEED ; Luis Antonio DÍAZ ; Antonio GIL-GÓMEZ ; Jeremy BURTON ; Jasmohan S. BAJAJ ; Manuel ROMERO-GOMEZ ; Marco ARRESE ; Juan Pablo ARAB ; Mohammad Qasim KHAN
Clinical and Molecular Hepatology 2025;31(Suppl):S94-S111
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a significant global health issue, affecting over 30% of the population worldwide due to the rising prevalence of metabolic risk factors such as obesity and type 2 diabetes mellitus. This spectrum of liver disease ranges from isolated steatosis to more severe forms such as steatohepatitis, fibrosis, and cirrhosis. Recent studies highlight the role of gut microbiota in MASLD pathogenesis, showing that dysbiosis significantly impacts metabolic health and the progression of liver disease. This review critically evaluates current microbiome-centered therapies in MASLD management, including prebiotics, probiotics, synbiotics, fecal microbiota transplantation, and emerging therapies such as engineered bacteria and bacteriophage therapy. We explore the scientific rationale, clinical evidence, and potential mechanisms by which these interventions influence MASLD. The gut-liver axis is crucial in MASLD, with notable changes in microbiome composition linked to disease progression. For instance, specific microbial profiles and reduced alpha diversity are associated with MASLD severity. Therapeutic strategies targeting the microbiome could modulate disease progression by improving gut permeability, reducing endotoxin-producing bacteria, and altering bile acid metabolism. Although promising, these therapies require further research to fully understand their mechanisms and optimize their efficacy. This review integrates findings from clinical trials and experimental studies, providing a comprehensive overview of microbiome-centered therapies’ potential in managing MASLD. Future research should focus on personalized strategies, utilizing microbiome features, blood metabolites, and customized dietary interventions to enhance the effectiveness of these therapies.
2.Microbiome-centered therapies for the management of metabolic dysfunction-associated steatotic liver disease
Huma SAEED ; Luis Antonio DÍAZ ; Antonio GIL-GÓMEZ ; Jeremy BURTON ; Jasmohan S. BAJAJ ; Manuel ROMERO-GOMEZ ; Marco ARRESE ; Juan Pablo ARAB ; Mohammad Qasim KHAN
Clinical and Molecular Hepatology 2025;31(Suppl):S94-S111
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a significant global health issue, affecting over 30% of the population worldwide due to the rising prevalence of metabolic risk factors such as obesity and type 2 diabetes mellitus. This spectrum of liver disease ranges from isolated steatosis to more severe forms such as steatohepatitis, fibrosis, and cirrhosis. Recent studies highlight the role of gut microbiota in MASLD pathogenesis, showing that dysbiosis significantly impacts metabolic health and the progression of liver disease. This review critically evaluates current microbiome-centered therapies in MASLD management, including prebiotics, probiotics, synbiotics, fecal microbiota transplantation, and emerging therapies such as engineered bacteria and bacteriophage therapy. We explore the scientific rationale, clinical evidence, and potential mechanisms by which these interventions influence MASLD. The gut-liver axis is crucial in MASLD, with notable changes in microbiome composition linked to disease progression. For instance, specific microbial profiles and reduced alpha diversity are associated with MASLD severity. Therapeutic strategies targeting the microbiome could modulate disease progression by improving gut permeability, reducing endotoxin-producing bacteria, and altering bile acid metabolism. Although promising, these therapies require further research to fully understand their mechanisms and optimize their efficacy. This review integrates findings from clinical trials and experimental studies, providing a comprehensive overview of microbiome-centered therapies’ potential in managing MASLD. Future research should focus on personalized strategies, utilizing microbiome features, blood metabolites, and customized dietary interventions to enhance the effectiveness of these therapies.
3.Microbiome-centered therapies for the management of metabolic dysfunction-associated steatotic liver disease
Huma SAEED ; Luis Antonio DÍAZ ; Antonio GIL-GÓMEZ ; Jeremy BURTON ; Jasmohan S. BAJAJ ; Manuel ROMERO-GOMEZ ; Marco ARRESE ; Juan Pablo ARAB ; Mohammad Qasim KHAN
Clinical and Molecular Hepatology 2025;31(Suppl):S94-S111
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a significant global health issue, affecting over 30% of the population worldwide due to the rising prevalence of metabolic risk factors such as obesity and type 2 diabetes mellitus. This spectrum of liver disease ranges from isolated steatosis to more severe forms such as steatohepatitis, fibrosis, and cirrhosis. Recent studies highlight the role of gut microbiota in MASLD pathogenesis, showing that dysbiosis significantly impacts metabolic health and the progression of liver disease. This review critically evaluates current microbiome-centered therapies in MASLD management, including prebiotics, probiotics, synbiotics, fecal microbiota transplantation, and emerging therapies such as engineered bacteria and bacteriophage therapy. We explore the scientific rationale, clinical evidence, and potential mechanisms by which these interventions influence MASLD. The gut-liver axis is crucial in MASLD, with notable changes in microbiome composition linked to disease progression. For instance, specific microbial profiles and reduced alpha diversity are associated with MASLD severity. Therapeutic strategies targeting the microbiome could modulate disease progression by improving gut permeability, reducing endotoxin-producing bacteria, and altering bile acid metabolism. Although promising, these therapies require further research to fully understand their mechanisms and optimize their efficacy. This review integrates findings from clinical trials and experimental studies, providing a comprehensive overview of microbiome-centered therapies’ potential in managing MASLD. Future research should focus on personalized strategies, utilizing microbiome features, blood metabolites, and customized dietary interventions to enhance the effectiveness of these therapies.
4.Robotic colorectal surgery training: Portsmouth perspective
Guglielmo Niccolò PIOZZI ; Sentilnathan SUBRAMANIAM ; Diana Ronconi DI GIUSEPPE ; Rauand DUHOKY ; Jim S. KHAN
Annals of Coloproctology 2024;40(4):350-362
This study aims to discuss the principles and pillars of robotic colorectal surgery training and share the training pathway at Portsmouth Hospitals University NHS Trust. A narrative review is presented to discuss all the relevant and critical steps in robotic surgical training. Robotic training requires a stepwise approach, including theoretical knowledge, case observation, simulation, dry lab, wet lab, tutored programs, proctoring (in person or telementoring), procedure-specific training, and follow-up. Portsmouth Colorectal has an established robotic training model with a safe stepwise approach that has been demonstrated through perioperative and oncological results. Robotic surgery training should enable a trainee to use the robotic platform safely and effectively, minimize errors, and enhance performance with improved outcomes. Portsmouth Colorectal has provided such a stepwise training program since 2015 and continues to promote and augment safe robotic training in its field. Safe and efficient training programs are essential to upholding the optimal standard of care.
5.Systematic review of validation studies for the use of wearable smartwatches in the screening of atrial fibrillation
Muhammad Samsoor ZARAK ; Sher Ali KHAN ; Harris MAJEED ; Abdul Qahar Khan YASINZAI ; Wadana HAMZAZAI ; Duy CHUNG ; Gregory KOSHKARIAN ; Kevin S. FLEMING
International Journal of Arrhythmia 2024;25(2):11-
WSWs have the potential to reliably and continuously screen for AFib and detect it in a timely manner.The inconclusive results produced by WSWs are a significant problem. Once the inconclusive results are rectified, WSWs may be used for widespread screening of AFib in those people who are at high risk of developing AFib.
6.Outcomes of Portosystemic Shunts in Children with and without Liver Transplantation
Hamza Hassan KHAN ; Stuart S. KAUFMAN ; Nada A. YAZIGI ; Khalid M. KHAN
Pediatric Gastroenterology, Hepatology & Nutrition 2024;27(1):37-42
Purpose:
Limited data exist regarding outcome and morbidity associated with portosystemic shunts in the pediatric transplant population. Our study assesses the outcomes of pediatric patients who underwent a portosystemic shunt procedure, both with and without liver transplantation (LT).
Methods:
This study retrospectively reviewed the medical records of pediatric patients aged 0–19 years who underwent shunt placement between 2003 and 2017 at a tertiary care center.The analysis included cases of shunt placement with or without LT.
Results:
A total of 13 pediatric patients were included in the study with median age of 8.8 years. Among the cases, 11 out of 13 (84.6%) underwent splenorenal shunt, 1 (7.7%) underwent a mesocaval shunt, and another 1 (7.7%) underwent a Modified Rex (mesoportal) shunt. Additionally, 5 out of 13 (38.5%) patients had LT, with 4 out of 5 (80.0%) receiving the transplant before shunt placement, and 1 out of 5 (20.0%) receiving it after shunt placement.Gastrointestinal bleeding resulting from portal hypertension was the indication in all cases.A total of 10 complications were reported in 5 patients; the most common complication was anemia in 3 (23.1%) patients. At the most recent follow-up visit, the shunts were functional without encephalopathy, and no deaths were reported.
Conclusion
Shunt placement plays a crucial role in the management of patients with portal hypertension. Our study demonstrates favorable long-term outcomes in pediatric patients who underwent shunt placement. Long term shunt outcomes were similar and unremarkable in patients with LT and without LT.
7.Molecular prevalence of Anaplasma marginale in ruminants and Rhipicephalus ticks in northern Pakistan
Ali, S. ; Hasan, M. ; Ahmad, A.S. ; Ashraf, K. ; Khan, J.A. ; Rashid, M.I.
Tropical Biomedicine 2023;40(No.1):7-13
Anaplasma marginale is the most prevalent tick-borne haemoparasite of cattle and causes huge
economic losses to the dairy industry worldwide. This study aimed to determine the occurrence of A.
marginale infection in blood and tick samples collected from livestock animals in the districts located
in Khyber Pakhtunkhwa (KPK), Pakistan. A total of 184 blood and 370 tick samples were included in this
study. It has never been reported that sheep, goats, and cattle in Tank, Ghulam Khan, Birmil and Miran
Shah areas were infected with A. marginale. All samples of blood and ticks were collected through
random sampling from March 2021 to January 2022 from cattle, sheep and goats and screened through
PCR for anaplasmosis by using primer pairs of Anaplasma spp. Three hundred and seventy ticks were
collected from infested hosts (120/184, 64.21%). Among the four morphologically identified tick species,
the highest occurrence was recorded for Rhipicephalus sanguineus (n=138, 37.29%), followed by
Rhipicephalus microplus (n=131, 35.4%), Rhipicephalus annulatus (n=40, 10.81%), Hyalomma anatolicum
(n=31, 8.37%), and Hyalomma marginatum (n=30, 8.1%). The occurrence of female tick was highest
(n=160, 43.24%), followed by nymphs (n=140, 37.38%) and males ticks (n=70, 18.9%). Among these ticks,
A. marginale was detected in female ticks of R. microplus, and R. sanguineus. Molecular identification
of A. marginale was confirmed in 120 out of 184 blood samples and 6 out of 74 tick samples. Overall,
occurrence of A. marginale in blood and tick samples was found to be 65.21% and 8.1% respectively.
Species-wise occurrence in blood samples of goats were 71.11% followed by sheep 68.31% and cattle
50%. Specie-wise occurrence of A. marginale in tick samples of cattle were 12.5% followed by goats
6.89%. The obtained sequence showed similarity with A. marginale reported from Kenya and USA. We
report the first PCR based detection of A. marginale infection in blood samples and in R. sanguineus
ticks of goats simultaneously.
8.How the Commonwealth of the Northern Mariana Islands stalled COVID-19 for 22 months and managed its first significant community transmission
Dwayne Davis ; Stephanie Kern-Allely ; Lily Muldoon ; John M Tudela ; Jesse Tudela ; Renea Raho ; Heather S Pangelinan ; Halina Palacios ; John Tabaguel ; Alan Hinson ; Guillermo Lifoifoi ; Warren Villagomez ; Joseph R Fauver ; Haley L Cash ; Esther Muñ ; a ; Sean T Casey ; Ali S Khan
Western Pacific Surveillance and Response 2023;14(1):76-85
Objective: The Commonwealth of the Northern Mariana Islands (CNMI) is a remote Pacific island territory with a population of 47 329 that successfully prevented the significant introduction of coronavirus disease (COVID-19) until late 2021. This study documents how the response to the introduction of COVID-19 in CNMI in 2021 was conducted with limited resources without overwhelming local clinical capacity or compromising health service delivery for the population.
Methods: Data from COVID-19 case investigations, contact tracing, the Commonwealth’s immunization registry and whole genome sequencing were collated and analysed as part of this study.
Results: Between 26 March 2020 and 31 December 2021, 3281 cases and 14 deaths due to COVID-19 were reported in CNMI (case fatality rate, 0.4%). While notification rates were highest among younger age groups, hospitalization and mortality rates were disproportionately greater among those aged >50 years and among the unvaccinated. The first widespread community transmission in CNMI was detected in October 2021, with genomic epidemiology and contact tracing data indicating a single introduction event involving the AY.25 lineage and subsequent rapid community spread. Vaccination coverage was high before widespread transmission occurred in October 2021 and increased further over the study period.
Discussion: Robust preparedness and strong leadership generated resilience within the public health sector such that COVID-19 did not overwhelm CNMI’s health system as it did in other jurisdictions and countries around the world. At no point was hospital capacity exceeded, and all patients received adequate care without the need for health-care rationing.
9.Simultaneous Correction of a Tibia Deformity and Non-union in Achondroplasia: A Case Report
Achudan S ; Premchand AXR ; Low JS ; Decruz J ; Khan SA
Malaysian Orthopaedic Journal 2022;16(No.2):131-135
Tibial non-union with deformity in abnormal bone is rarely
reported in literature. We report a case of a 65 years old male
with a history of achondroplasia. The patient presented after
a mechanical fall with an undisplaced right midshaft tibia
fracture associated with pre-existing varus and procurvatum
tibial deformities, which was initially managed nonoperatively. However, after nine months he developed a
painful non-union. Because of the symptomatic non-union as
well as the pre-existing deformities, osteotomy of the tibia
and fibula was performed with the application of a TruelokHexapod (TL-Hex, Orthofix) frame. We were able to achieve
compression at the fracture site, and the software guided TLHex frame enabled gradual three-dimensional correction of
the deformity. At six months, bony union and simultaneous
correction of the tibia deformity were achieved. At two
years, the patient was able to ambulate well without pain and
perform his activities of daily living. We present a case of
tibial non-union with pre-existing deformity in an
achondroplasia patient successfully treated with a circular
frame application.
10.Efficacy of pentamidine-loaded chitosan nanoparticles as a novel drug delivery system for Leishmania tropica
Khan, R.U. ; Khan, M. ; Sohail, A. ; Ullah, R. ; Iqbal, A. ; Ahmad, B. ; Khan, I.U. ; Tariq, A. ; Ahmad, M. ; Said, A. ; Ullah, S. ; Ali, A. ; Rahman, M.U. ; Zaman, A. ; Bilal, H.
Tropical Biomedicine 2022;39(No.4):511-517
The present study compares the in vitro effects of nanoparticles loaded pentamidine drug and
conventional pentamidine on Leishmania tropica. Herein, pentamidine-loaded chitosan nanoparticles
(PTN-CNPs) have been synthesized through an ionic gelation method with sodium tripolyphosphate
(TPP). Next, the physical characteristics of PTN-CNPs were determined through the surface texture,
zeta potential, in vitro drug release, drug loading content (DLC), and encapsulation efficacy (EE) and
compared its efficacy with free pentamidine (PTN) drug against promastigotes and axenic amastigotes
forms of L. tropica in vitro. The PTN-CNPs displayed a spherical shape having a size of 88 nm, an
almost negative surface charge (-3.09 mV), EE for PTN entrapment of 86%, and in vitro drug release
of 92% after 36 h. In vitro antileishmanial activity of PTN-CNPs and free PTN was performed against
Leishmania tropica KWH23 promastigote and axenic amastigote using 3-(4, 5- dimethylthiazol-2-yl)-2,
5-diphenyletetrazolium bromide (MTT) assay. It was observed that the effect of PTN-CNPs and free
PTN on both forms of the parasite was dose and time dependent. Free PTN presented low efficacy even
at higher dose (40 µg/ml) with 25.6 ± 1.3 and 26.5 ±1.4 mean viability rate of the promastigotes and
axenic amastigotes, respectively after 72 hrs incubation. While PTN-CNPs showed strong antileishmanial
effects on both forms of parasite with 16 ± 0.4 and 19 ± 0.7 mean viability rate at the same higher
concentration (40 µg/ml) after 72 hrs incubation. Half maximal inhibitory concentration (IC50) values
of PTN-CNPs toward promastigotes and amastigotes were obtained as 0.1375 µg/ml and 0.1910
µg/ml, respectively. In conclusion, PTN-CNPs effectively inhibited both forms of the L. tropica; however,
its effect was more salient on promastigotes. This data indicates that the PTN-CNPs act as a target drug
delivery system. However, further research is needed to support its efficacy in animal and human CL.


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