Steatotic Donor Transplant Livers: Preservation Strategies to Mitigate against Ischaemia-Reperfusion Injury.

Liver transplantation (LT) is the only definitive treatment for end-stage liver disease, yet the UK has seen a 400% increase in liver disease-related deaths since 1970, constrained further by a critical shortage of donor organs. This shortfall has necessitated the use of extended criteria donor organs, including those with evidence of steatosis. The impact of hepatic steatosis (HS) on graft viability remains a concern, particularly for donor livers with moderate to severe steatosis which are highly sensitive to the process of ischaemia-reperfusion injury (IRI) and static cold storage (SCS) leading to poor post-transplantation outcomes. This review explores the pathophysiological predisposition of steatotic livers to IRI, the limitations of SCS, and alternative preservation strategies, including novel organ preservation solutions (OPS) and normothermic machine perfusion (NMP), to mitigate IRI and improve outcomes for steatotic donor livers. By addressing these challenges, the liver transplant community can enhance the utilisation of steatotic donor livers which is crucial in the context of the global obesity crisis and the growing need to expand the donor pool.

RATE AND INDICATIONS OF ELECTIVE AND EMERGENCY CAESAREAN SECTION; A STUDY IN A TERTIARY CARE HOSPITAL OF PESHAWAR.

BACKGROUND: The study was conducted to determine the rate and clinical indications for emergency and elective caesarean section. METHODS: This was a cross-sectional descriptive study conducted from December 2010 to January 2011 in Gynaecology unit-A of Lady Reading Hospital Peshawar. Consecutive patients who gave birth in the hospital during the study period were included in the study. There were a total of 966 patients. Mode of delivery and basic demographics of the patients who underwent elective and emergency caesarean section were noted down. Clinical indications were recorded. RESULTS: Out of 966 patients, 210 underwent caesarean section. Therefore, the rate of caesarean section was 21.7 per 100. Among those 78% (n=164) were emergency caesarean sections and others were elective caesarean sections. Top six indicators for caesarean sections were foetal distress 17.1% (n=36), obstructive labour/failure to progress 16.1% (n=34), previous caesarean section 15.2% (n=32), breech presentation 9.5% (n=20), cephalopelvic disproportion 6.1% (n=13), failed induction 5.7% (n=12) and pregnancy induced hypertension (PIH) 5.7% (n=12). CONCLUSION: The rate of caesarean section was only slightly higher than recommended by the WHO. Most of caesarean sections were emergency caesarean sections.

SENSITIVITY PATTERNS OF PSEUDOMONAS AERUGINOSA ISOLATES OBTAINED FROM CLINICAL SPECIMENS IN PESHAWAR.

BACKGROUND: Pseudomonas aeruginosa (P. aeruginosa) is a highly virulent opportunistic pathogen and a leading cause of nosocomial infections. Affected patients are often hospitalized in an intensive care unit, and are immuno-compromised as a result of disease and treatment. Suspected P. aeruginosa require timely, adequate and empirical antibiotic therapy to ensure improved outcomes. The purpose of the study was to find the sensitivity and resistance pattern of P. aeruginosa to various groups of drugs, in clinical isolates collected from two major tertiary care hospitals of Peshawar. METHODS: Different clinical isolate were taken from patients admitted in various wards of Khyber Teaching Hospital and Lady Reading Hospital Peshawar. RESULTS: A total of 258 clinical isolates were positive for P. aeruginosa out of 2058 clinical isolates. Pseudomonas showed high degree of resistance to third generation Cephalosporins (Ceftazidime, and Ceftriaxone) and moderate degree of resistance to Quinolones and Aminoglycosides (Ofloxacin, Ciprofloxacin, Levofloxacin and Amikacin). Low resistance was observed to different combinations (Cefoperazone+Sulbactum, Piperacillin+Tazobactum). Meropenem and Imipenem had negligible resistance. CONCLUSION: There is growing resistance to different classes of antibiotics. Combination drugs are useful approach for empirical treatment in suspected Pseudomonas infection. Imipenem and Meropenem are extremely effective but should be in reserve.

Defatting of donor transplant livers during normothermic perfusion-a randomised clinical trial: study protocol for the DeFat study.

BACKGROUND: Liver disease is the third leading cause of premature death in the UK. Transplantation is the only successful treatment for end-stage liver disease but is limited by a shortage of suitable donor organs. As a result, up to 20% of patients on liver transplant waiting lists die before receiving a transplant. A third of donated livers are not suitable for transplant, often due to steatosis. Hepatic steatosis, which affects 33% of the UK population, is strongly associated with obesity, an increasing problem in the potential donor pool. We have recently tested defatting interventions during normothermic machine perfusion (NMP) in discarded steatotic human livers that were not transplanted. A combination of therapies including forskolin (NKH477) and L-carnitine to defat liver cells and lipoprotein apheresis filtration were investigated. These interventions resulted in functional improvement during perfusion and reduced the intrahepatocellular triglyceride (IHTG) content. We hypothesise that defatting during NMP will allow more steatotic livers to be transplanted with improved outcomes. METHODS: In the proposed multi-centre clinical trial, we will randomly assign 60 livers from donors with a high-risk of hepatic steatosis to either NMP alone or NMP with defatting interventions. We aim to test the safety and feasibility of the defatting intervention and will explore efficacy by comparing ex-situ and post-reperfusion liver function between the groups. The primary endpoint will be the proportion of livers that achieve predefined functional criteria during perfusion which indicate potential suitability for transplantation. These criteria reflect hepatic metabolism and injury and include lactate clearance, perfusate pH, glucose metabolism, bile composition, vascular flows and transaminase levels. Clinical secondary endpoints will include proportion of livers transplanted in the two arms, graft function; cell-free DNA (cfDNA) at follow-up visits; patient and graft survival; hospital and ITU stay; evidence of ischemia-reperfusion injury (IRI); non-anastomotic biliary strictures and recurrence of steatosis (determined on MRI at 6 months). DISCUSSION: This study explores ex-situ pharmacological optimisation of steatotic donor livers during NMP. If the intervention proves effective, it will allow the safe transplantation of livers that are currently very likely to be discarded, thereby reducing waiting list deaths. TRIAL REGISTRATION: ISRCTN ISRCTN14957538. Registered in October 2022.

Cataract: trends in surgical procedures and visual outcomes; a study in a tertiary care hospital.

OBJECTIVE: To determine the current procedures in practice and visual outcome following a cataract surgery. METHODS: The study was conducted from January 7 to April 7, 2011 in the Eye Unit of the Lady Reading Hospital, Peshawar, involving 181 patients. Basic demographics of the patients as well as the type of cataract surgery were noted. Risk factors like diabetes mellitus and glaucoma were also noted for each patient. A pre-operative visual acuity was determined. The patient was examined after two months to determine the visual improvement. RESULTS: Out of 181 patients, 117 were males and 64 were females. Age ranged from 5 years to 83 years with a median age of 60. Most common procedure performed (60.2%) was extra capsular cataract extraction with posterior chamber intraocular lense (ECCE), followed by Phacoemulsification (24.3%). Visual outcome was good in 88.3%, borderline in 8.3% and poor in 3.3% patients. The main reasons for poor visual outcomes were diabetic retinopathy 42.8%, glaucoma-related vision loss 19.0%, history of trauma with retinal detachment 9.5%, and age-related macular degeneration 9.5%. Poor visual outcome was found in diabetic and Glaucoma patients. Surgical complications (3.8%) were rare. CONCLUSION: Overall a good visual outcome was noted in cataract surgery, which was similar to World Health Organisation guidelines. Extra capsular cataract extraction was the most common procedure followed by Phacoemulsification.

Factors associated with low hepatitis B vaccination; a user and provider perspective study in Peshawar.

Hepatitis B is a major burden in Pakistan. A cross-sectional study was conducted in Peshawar, from 9th June to 19th June 2010. Cluster random sampling was done. Confidence level of 95% and confidence interval of 5 was used to derive sample size. Parents of 506 children were asked about their hepatitis B immunization status who were aged 4 years or under. Questions on demographics, income, education, accessibility and occupation, knowledge and views on immunization were asked. Forty health personnel were interviewed for their views. In all, 62.2% children were completely vaccinated. Reasons for not being immunized included unawareness, busy schedule, long distance to the centre and various misconceptions. Education, mothers' knowledge and views on immunization, income, closer accessibility, were the main factors associated with immunization. Health personnel thought lack of awareness among people, low accessibility and poor incentives as the shortcomings in immunization. It is recommended that effective steps should be taken to ensure better coverage.

Coverage and causes of missed oral polio vaccine in urban and rural areas of Peshawar.

BACKGROUND: Poliomyelitis mainly affects children under five years of age. Pakistan is one of the few countries where wild polio is still endemic. The purpose of this study was to find out the coverage rate and factors associated with the failure of OPV in urban and rural areas of Peshawar. METHODS: This cross-sectional study was conducted in Peshawar. Data was collected through random sampling in Peshawar University, Peshawar Saddar, Hashtnagri, Naway Kalay and Pawaka from 9th to 19th June 2010. A questionnaire was used to interview parents of 548 children, aged four years and below, about demographics, OPV vaccination status, reasons for missed vaccination and views on immunization and EPI staff. Forty workers from immunization staff were also interviewed through a separate questionnaire to find out factors associated with low OPV coverage. Chi-square test was used for statistical testing and p < 0.05 was considered significant. RESULTS: Only 64.2% children were completely vaccinated, 13.3 % not vaccinated at all, and 22.4% were incompletely vaccinated. The reasons for not vaccinating were lack of awareness (23.8%), family problem/mother busy (20.8%), centre too far (21.3%), wrong ideas (10.2%), fear of reaction (7.6%), child ill (5.6%) and miscellaneous causes (10.6%). The problems faced by the EPI staff were lack of awareness among people (32.5%), load shedding (20.0%), poor transport facilities (10.0%), unavailability of vaccines (10.0%) and insecurity (10.0%). CONCLUSION: Low vaccination coverage in Peshawar is mainly due to low awareness among people, poor economic conditions and poor salaries, insecurity and transport problems faced by the immunization staff.

Inequity in childhood immunization between urban and rural areas of Peshawar.

BACKGROUND: Purpose of this study was to find coverage of vaccines in EPI and compare the factors related to vaccine failure or missed vaccination in urban and rural areas of Peshawar. METHODS: This cross-sectional survey was conducted in Urban and rural of Peshawar from 20th to 31st of June 2010. A questionnaire was used to interview parents of 548 children, aged 1 year and below, about demographics, vaccination status, reasons for missed vaccination and views on immunization. Results from both urban and rural areas were compared to find the impact of different factors on immunization failure. RESULTS: The immunization coverage in urban areas was 76.5% while in rural areas it was 48.8%. Causes for non immunization were different in urban and rural areas. In urban areas, lack of awareness and care takers/parents being busy were the main reason for non immunization. In rural areas, in addition to formers, lack of accessibility to health centres and misconceptions about vaccination were major reasons for non-immunization. Parents were more educated in urban areas than rural areas. CONCLUSION: Rural areas had a lower immunization rates due to lack of awareness, low accessibility and much lower education of parents.

Coverage and causes of missed Haemophilus influenzae type B vaccination in urban and rural areas of Peshawar.

BACKGROUND: Haemophilus influenza type b (Hib) is a major cause of morbidity and mortality in Pakistan. Hib vaccine was introduced in 2009 in EPI programme. The purpose of this study was to find out the coverage and factors associated with non-immunization of Hib in urban and rural areas of Peshawar. METHODS: Data was collected through random sampling in Peshawar University, Peshawar Saddar, Hashtnagri, Naway Kalay and Pawaka from 9th to 19th of June 2010. A questionnaire was used to interview parents of 600 children aged 1 year and below about demographics, Hib vaccination status, reasons for missed vaccination and views on immunization. Pearson's Chi-square test was used for statistical testing, and p<0.05 was considered significant. RESULTS: Completely vaccinated children were 64.2%, 25% not vaccinated at all, and 11% were incompletely vaccinated. The reasons for not vaccinating were lack of awareness (26%), family problem/mother busy (18%), centre too far (16.9%), wrong ideas (12.2%), fear of reaction (5.4%), child illness (8.1%) and miscellaneous causes (13.7%). CONCLUSION: Low Hib vaccination coverage in Peshawar is mainly due to low awareness among people, poor economic conditions and illiteracy.

Coverage and factors associated with tetanus toxoid vaccination among married women of reproductive age: a cross sectional study in Peshawar.

BACKGROUND: Pakistan has one of the highest maternal mortality rates in the world, with widely prevalent maternal and neonatal tetanus. The purpose of this study was to estimate the coverage and determine the factors associated with tetanus toxoid vaccination status among females of reproductive age in Peshawar. METHODS: A Cross-sectional study was conducted in Peshawar, Pakistan, from 9 June to 19 June 2010. A total of 304 females of reproductive age (17 45) years were selected from both urban and rural areas of Peshawar through random sampling. A pre-tested structured questionnaire was administered to females. Questions about demographics, income, education of husband, occupation, accessibility to health centres and frequency of visits from health workers was inquired. Knowledge and views on immunization were also asked. RESULTS: Overall 55.6% were vaccinated. Urban population was 54.3% while rural population was 45.7%. Reasons for not vaccinating were: No awareness (38.4%), being busy (18.1%), centre too far (18.1%), misconceptions (10.86%), and fear of reactions (4.3%). Most of the females thought immunization was effective (89.5%). Husband education, females' knowledge and views on immunization, income, distance, frequency of health visits were the main factors associated with immunization status. CONCLUSION: Majority of females are not vaccinated. Effective media campaigns on maternal tetanus vaccination should be carried. Lady health workers should be mobilised effectively to increase the vaccination coverage.

Cutaneous Cholangiocarcinoma: An Interesting Presentation.

This is a case of a 64-year-old white man with a history of CCA, originally diagnosed in May 2018 and returning in November 2019 with growing cutaneous nodules. These were removed for cosmetic and functional purposes. Pathologic findings of the lesions showed likely metastatic disease from his original CCA. This represents a relatively rare presentation of metastatic disease in the setting of CCA. In cases of CCA with metastatic spread, treatment is not curative and should be focused on measures to improve the patient's quality of life. This includes acceptable cosmesis, as well as factors aiding in completing activities of daily living.

Normothermic Machine Perfusion (NMP) of the Liver as a Platform for Therapeutic Interventions during Ex-Vivo Liver Preservation: A Review.

Liver transplantation is increasingly dependent on the use of extended criteria donors (ECD) to increase the organ donor pool and address rising demand. This has necessitated the adoption of innovative technologies and strategies to protect these higher-risk grafts from the deleterious effects of traditional preservation and ischaemia reperfusion injury (IRI). The advent of normothermic machine perfusion (NMP) and rapid growth in the clinical adoption of this technology has accelerated efforts to utilise NMP as a platform for therapeutic intervention to optimise donor livers. In this review we will explore the emerging preclinical data related to ameliorating the effects of IRI, protecting the microcirculation and reducing the immunogenicity of donor organs during NMP. Exploiting the window of opportunity afforded by NMP, whereby the liver can be continuously supported and functionally assessed while therapies are directly delivered during the preservation period, has clear logistical and theoretical advantages over current preservation methods. The clinical translation of many of the therapeutic agents and strategies we will describe is becoming more feasible with widespread adaptation of NMP devices and rapid advances in molecular biology and gene therapy, which have substantially improved the performance of these agents. The delivery of novel therapeutics during NMP represents one of the new frontiers in transplantation research and offers real potential for successfully tackling fundamental challenges in transplantation such as IRI.

Primary Pancreatic lymphoma: a rare clinical entity.

Primary pancreatic lymphoma is a rare clinical entity representing <0.5% of pancreatic cancers and 1% of extranodal lymphomas. Due to the paucity of cases described in the literature, its clinicopathological features, differential diagnosis, optimal therapy and outcomes are not well defined. As the clinical manifestations are often non-specific, it can create a diagnostic pitfall for the unwary physician. Preoperative distinction of adenocarcinoma and primary pancreatic lymphoma is critical since the management and prognosis of these malignancies are mutually exclusive. Due to its rarity, epidemiological studies have been difficult to conduct. Chemotherapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin and vincristine) has proven to be effective. The authors present the case of a 52-year-old man with epigastric pain and obstructive jaundice. Further investigation with a CT of the abdomen and pelvis showed a low attenuation mass in the head of the pancreas measuring 35×25 mm, suspicious for malignancy. The mass involved the common bile duct distally causing moderate retrograde intrahepatic and extrahepatic biliary tree dilation of 14 mm. He underwent endoscopic retrograde cholangiopancreatography, sphincterotomy and insertion of a stent. Core biopsies confirmed the diagnosis of a high-grade B cell pancreas lymphoma. He started treatment with R-CHOP and prednisolone. Due to disease progression, he started treatment with DA-EPOCH-R (etoposide phosphate, prednisone, vincristine sulfate, cyclophosphamide, doxorubicin hydrochloride and rituximab). There was no clinical response, and treatment with RICE (rituximab, ifosfamide, carboplatin and etoposide) was initiated. He showed partial response and was under consideration for chimeric antigen receptor T cell therapy. He deteriorated clinically and succumbed to his disease 5 months following his initial presentation. This paper will provide an overview of the spectrum of haematological malignancies and describe useful features in distinguishing primary lymphoma of the pancreas from an adenocarcinoma, hence avoiding its surgical resection.

Comparison of 'Excision and Primary Repair' with 'Bascom's Technique' in the Surgical Treatment of Pilonidal Sinus.

Introduction The management of the chronic pilonidal disease is variable and the principles of treatment are aimed to eradicate the sinus tract, promote wound healing, prevent disease recurrence, and improve the quality of life of the patient. This study aims to compare the effectiveness of excision and primary closure, and Bascom's technique in the management of pilonidal sinus disease. Methods  The study was performed at a tertiary hospital from April to October 2011. All patients with chronic pilonidal sinus were included in the study (n=60) and randomly allocated into Group A - undergoing excision and primary closure (n=30) and Group B - undergoing Bascom's repair. Comparative outcomes of interest were duration of hospital admission, post-operative pain, wound infection, wound-healing and disease recurrence.  Results The mean age of presentation was 24.18±5.6 years. A higher number of patients in Group A were discharged within 24 hours compared to Group B (p = 0.001). Group B had significantly less post-operative pain by the first postoperative week (p = 0.049). Group B had lower infection rates with clean wounds observed in 28 (93.3%) patients compared to 23 (76.7%) in Group A by the first postoperative week (p = 0.07). Recurrence rate during 12-week follow-up was observed in one (3.3%) patient in Group B, and five (16.7%) in Group A (p= 0.085). Conclusions Patients who underwent Bascom's operation had less postoperative pain, lower infection rates and disease recurrence, and better wound healing. Therefore, in our patient cohort, we conclude Bascom's repair appears to be superior to primary excision and repair in reducing patient morbidity.

Spontaneous splenic rupture: a rare first presentation of diffuse large B cell lymphoma.

Spontaneous splenic rupture (SSR) is a rare but potentially life-threatening entity. It can be due to neoplastic, infectious, haematological, inflammatory and metabolic causes. An iatrogenic or an idiopathic aetiology should also be considered. Depending on the degree of splenic injury and the haemodynamic status of the patient, it can be managed conservatively. A 61-year-old man presented to the emergency department with an acute abdomen, hypovolaemic shock and clotting abnormalities. However, his focused assessment with sonography for trauma showed no evidence of an aortic aneurysm, rupture or dissection. Further investigation with a CT angiogram aorta confirmed a subcapsular splenic haematoma with free fluid in the pelvis and a mass in the superior pole of the spleen. He was diagnosed with an SSR. He was initially managed non-operatively. However, his repeat CT showed an enlarging haematoma and he underwent embolisation of his splenic artery. Ultrasound-guided core biopsy of his splenic mass confirmed the diagnosis of diffuse large B-cell lymphoma. This paper will discuss the clinical presentation, differential diagnosis and management of SSR. Furthermore, it provides an important clinical lesson to maintain a high index of clinical suspicion for splenic injury in patients presenting with left upper quadrant abdominal pain radiating to the shoulder. This case also reinforces the importance of close observation and monitoring of those individuals treated conservatively for signs of clinical deterioration.

Newborn with a rare congenital granular cell lesion of the tongue.

Congenital granular cell lesion (CGCL) is an uncommon, benign soft tissue lesion that usually arises from the alveolar mucosa of neonates. The present report describes a case of CGCL originating from the tongue of a newborn female infant. The lesion was negative for S-100 differentiating it from congenital granular cell tumour. The lesion was excised under local anaesthesia with no recurrence at 4 months.

The Effect of Bariatric Surgery on Patients with HIV Infection: a Literature Review.

Obesity among human immunodeficiency virus (HIV)-infected individuals is on the rise. Bariatric procedures such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) alter the GI tract. Whether this alteration has any impact on the absorption of highly active antiretroviral therapy (HAART), thus affecting HIV disease markers such as CD4 cell count or viral load (VL), is not yet known. We conducted this review to look into the outcomes of bariatric surgery procedures, RYGB, SG and adjustable gastric band (AGB) and its effects on the CD4 cell counts and VL and HAART therapy. A literature search was conducted between January and April 2017, by two independent reviewers, using Pubmed and Google Scholar. The terms 'bariatric surgery and HIV', 'obesity surgery and HIV', 'gastric bypass surgery and HIV', 'sleeve gastrectomy and HIV' and 'gastric band and HIV' were used to retrieve available research. Of the 49 papers reviewed, only 12 reported the outcomes of patients with HIV undergoing bariatric surgery and were therefore included in this review. Six papers assessed patients undergoing RYGB only (N = 18), 3 papers reported on SG only (N = 18) and 3 papers reported on case mix, including 7 cases of RYGB, 4 cases of SG and 11 cases of AGB. Data is limited; however, based on the available data, bariatric surgery is safe in HIV-infected individuals and does not have any adverse impact on HIV disease progress. Additionally, there was no difference in HIV-related outcomes between SG and RYGB.

Mesenteric Meckel's diverticulum: an unusual cause of small bowel intussusception.

Meckel's diverticulum (MD) is the commonest congenital anomaly of the small intestine, affecting 1-4% of the population. Cardinal features emphasise an antimesenteric location two feet proximal to the ileocaecal valve, with a separate mesenteric blood supply and involvement of all layers of the small intestine. However, reports of MD arising from the mesenteric border of the small intestine are rare in the surgical literature. This report examines the case of a 45-year-old woman presenting with a 6-month history of episodic central abdominal pain and microcytic anaemia who underwent an elective diagnostic laparoscopy as initial CT findings were inconclusive. Intraoperatively, she was found to have small bowel intussusception approximately 40 cm proximal to the ileocaecal valve. Macroscopic examination of the resected small bowel segment revealed a mesenteric outpouching that was confirmed as mesenteric MD on histopathological analysis. Postoperatively, the patient recovered with no surgical complications and full symptom resolution.

Metastatic hepatocellular carcinoma to the pelvis and vertebrae in a patient with chronic hepatitis 'C' with unknown primary.

A 54-year-old man infected with hepatitis C virus presented to us with pain in the right iliac fossa radiating to the back and right thigh for the past 2 months. Imaging of the abdomen and pelvis was performed, which revealed a soft tissue mass adherent to right iliac blade and right ala of sacrum. Trucut biopsy of the mass was performed and immunohistochemical stains Glypican-3 and Hep-par 1 were used for histopathological analysis, which diagnosed the mass as hepatocellular carcinoma. This is a unique case of metastasis of hepatocellular carcinoma to the bone in which imaging of the liver did not show any primary lesion. Liver function tests showed that aspartate transaminase and alanine transaminase were twice the normal range with a high viral load and significantly raised serum α-fetoprotein. The patient was treated with intravenous 5-flourouracil and radiotherapy as a palliative measure with only moderate clinical improvement.