Obstructed inguinal hernia containing ovary with an ovarian cyst: a case report.

A 27-year-old married woman came to the emergency room (ER) with the chief complaint of severe pain in the abdomen for 3 days, which was more pronounced in the right iliac fossa, along with the complaint of multiple episodes of vomiting for the last 6 hours. She also gave a history of swelling in the right inguinal region for last 9 months with the complaint of mild on and off pain in the swelling. On physical examination, diagnosis of obstructed inguinal hernia was made. Ultrasonography (USG) of abdomen was of no use, as it only commented on hernial defect and not on the contents of the hernial sac. An emergency surgery was planned; marsupialisation of ovarian cyst, repositioning of fallopian tube along with ovary and herniorrhaphy was performed without any difficulty.

Spontaneous splenic rupture during dengue fever.

Dengue fever is one of the most frequent arboviral diseases in the world. Dengue is known to cause myocarditis, hepatitis, and neurological illustrations but one of the established presentations is leakage of plasma resulting in circulatory failure. Spontaneous rupture of the spleen is one of the most infrequent but known outcome of dengue fever which has been reported from time to time in literature. We present, here, the case of a 50-year-old patient who developed this condition during dengue fever and was managed in our department successfully. This complication must be kept in mind while treating any case of dengue fever so that it can be avoided or if not then treated timely.

The study of frequency of malignancy and its types in surgical jaundice; a tertiary care experience.

OBJECTIVE: To determine the frequency of malignancy and its types in patients presenting with surgical jaundice in a tertiary care setting. METHODS: The cross-sectional study was conducted at the North Surgical Ward, Mayo Hospital, Lahore, Pakistan, from May 8 to November 8, 2020, and comprised patients of either gender with a diagnosis of surgical jaundice made on the basis of history, clinical examination, haematological and biochemical reports and radiological investigations. All patients were managed as per the guidelines for surgical jaundice with injection vitamin K intramuscular, hydration with intravenous fluids, avoidance of constipation by lactulose or neomycin, vitals and urine output monitoring and prophylactic antibiotics. Demographic data as well frequency of malignancy were noted using a predesigned proforma. Data was analysed using SPSS 21. RESULTS: Of the 95 patients, 51(53.7%) were male and 44(46.3%) were female. The overall mean age was 49.96±16.54 years (range: 18-80 years). A total of 19(20%) cases had body mass index <30. Malignancy was identified in 50(52.6%) cases; 14(28%) gallbladder, 4(8%) head of pancreas, 9(18%) peri-ampullary carcinoma, 7(14%) cholangiocarcinoma, 6(12%) Klastkin tumour, 5(10%) hepatocellular carcinoma, and 5(10%) metastatic tumour. CONCLUSIONS: More than half of the surgical jaundice cases had malignancy, gallbladder being the most affected site.

An outcome of emergency vascular surgery performed by general surgeons; our experience in a university hospital of Pakistan and can they substitute vascular surgeons?

OBJECTIVE: To measure the outcome of emergency vascular surgery performed by general surgeons, and to identify preventable causes of mortality. METHODS: The retrospective study was conducted at the General Surgery Department of Mayo Hospital, King Edward Medical University, Lahore, Pakistan, and comprised data between January 2014 and May 2019 related to cases regardless of age and gender that required emergency vascular surgery after diagnosis by a consultant surgeon at the surgical emergency. The cases were analysed from admission till discharge. Data was analysed using SPSS 20. RESULTS: Of the 135 cases, 127(94%) were males. The overall mean age was 28.8±11.5 years (range: 14-63 years). Mean duration of hospital stay was 11±3.92 days (range: 4-22 days). Three major peripheral arteries injured were brachial 32(38.5%), popliteal 55(40.7%) and femoral 20(20.7%), with more than half with complete transection 75(55.6%). Vascular repairs done were primary anastomosis 45(33.3%), reverse saphenous vein graft 68(50.4%), embolectomy 4(3%) and amputation 18(13.3%). Limb salvage rate and mortality was 101(74.8%) and 6(4.4%), respectively. Complications occurred in 38(28.1%) cases, with 24(18%) wound infections and 9(6.7%) myonecrosis. Factors leading to poor outcome/complications were Glasgow Coma Scale score <12 (p=0.01), referred case (p=0.04), significant bleeding (p=0.004), haemoglobin <9 at presentation (p=0.001), bone fracture (p=0.01), involvement of lower limb (p=0.003) and late presentation (p=0.003). CONCLUSIONS: Late presentation in hospital was the major modifiable factor improvement of which could lead to better outcome, apart from the early and proper surgical intervention.

A ruptured seventeen weeks' ectopic pregnancy: A case report.

Ectopic pregnancy is a common condition with a prevalence of 2% in all pregnancies. Implantation of the developing blastocyst outside the uterine cavity leads to ectopic pregnancy. About 95% of ectopic pregnancies occur in the different segments of the fallopian tubes. Usually, an ectopic pregnancy grows up to 1.5-3.5 cm and any size greater than this leads to rupture. We present a case of ruptured ectopic pregnancy in which the foetus had a crown-rump length(CRL) of 12 cm was retrieved. To our knowledge, this is the largest foetus recovered from a ruptured ectopic pregnancy at the ampulla of fallopian tube reported in the literature. Timely diagnosis and proper management is the key to reduce morbidity associated with it.

Surgical smoke; an occupational hazard.

Surgical smoke is part of the environment during operative and invasive procedures. Electric diathermy is a very important tool for a surgeon and is used in every surgical treatment nowadays. It assists the surgeon to dissect the tissue or enables securing haemostasis in lesser time and with larger delicacy. But at the same time, it has harmful effects on surgeon as well as patients. Although there is a substantial amount of evidence and guidelines from various authors and societies, yet there are no clear policies and preventive measures towards surgical smoke handling. This article presents potential harmful effects of surgical smoke and aims to build guidelines for the surgical personnel based on current evidence in literature.

Polymorphism in interferon λ3/interleukin-28B gene and risk to noncirrhotic chronic hepatitis C genotype 3 virus infection and its effect on the response to combined daclatasvir and sofosbuvir therapy.

Hepatitis C virus (HCV) infection is a considerable public-health problem and an important cause of liver disease with about 71 million people infected worldwide and more than 399 000 people die every year from hepatitis C-related liver diseases. The present study was, therefore, initiated to investigate the association of polymorphism in interferon λ3 (IFNL3) also known as interleukin-28B (IL-28B) gene with chronic HCV infection and association of these polymorphic variants with the combination daclatasvir and sofosbuvir HCV therapy response. Genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in a total of 250 chronic HCV genotype three patients and 500 number of healthy controls. Our data revealed that the TT (minor) genotype of IFNL3 (rs12979860) and GG (minor) genotype of IFNL3 (rs8099917) exhibited a significant association with chronic HCV genotype 3 infection when compared with controls. The results of treatment response showed that CC (major) genotype of IFNL3 (rs12979860) and TT (major) genotype of IFNL3 (rs8099917) are associated with the likelihood of achieving a higher sustained virological response (SVR), to combined daclatasvir and sofosbuvir therapy, in genotype 3-infected HCV patients, whereas the individuals with TT (minor) genotype of IFNL3 (rs12979860) and GG (minor) genotype of IFNL3 (rs8099917) are more susceptible to chronic HCV infection and treatment relapse, suggesting a role of IFNL3 (rs12979860) and (rs8099917) in the treatment outcome of combined daclatasvir and sofosbuvir therapy in chronic HCV genotype 3 infection.

Polymorphism in cytochrome P450 2E1 and interaction with other genetic risk factors and susceptibility to alcoholic liver cirrhosis.

The association of polymorphism in cytochrome P450 2E1 (CYP2E1), the major microsomal ethanol metabolizing enzyme and its interaction with genes, involved in detoxification of reactive oxygen species, such as glutathione-S-transferases M1 (GSTM1) and alcohol intake, gamma-aminobutyric acid receptor gamma2 (GABRG2) was studied with the risk to alcoholic cirrhosis in a case-control study. A total of 160 alcoholic cirrhotic and 125 non-alcoholic cirrhotic cases, visiting the OPD facility of Gastroenterology Department of Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGI), Lucknow, India and 250 non-alcoholic and 100 alcoholic controls having no evidence of liver disease were included in the study. PCR-based RFLP methodology was followed for genotyping studies. Our data revealed that the variant genotypes of CYP2E1 5B exhibited significant association with the alcoholic liver cirrhosis when compared to non-alcoholic controls (OR: 4.3; 95%CI: 1.5-12.4; p: 0.003) or non-alcoholic cirrhosis patients (OR: 5.4; 95%CI: 1.2-24.5; p: 0.01) or alcoholic controls (OR: 4.3; 95%CI: 0.95-19.62; p: 0.04). Haplotype approach revealed that haplotype T-A-T was found to be associated with more than 5-fold increase in risk for alcoholic cirrhosis. Likewise, combination of variant genotype of CYP2E1 5B with null genotype of GSTM1, a phase II detoxification enzyme, resulted in several fold increase in risk in alcoholic cirrhotic patients when compared with non-alcoholic controls or non-alcoholic cirrhotic patients. Further, the combination of variant genotype of CYP2E1 5B with GABRG2, significantly increased the risk upto 6.5-fold in alcoholic cirrhotic patients when compared with non-alcoholic controls thereby suggesting the role of gene-gene interaction in alcoholic cirrhosis.

Effect of low-level BCR-ABL1 kinase domain mutations identified by next-generation sequencing in patients with chronic myeloid leukaemia: a population-based study.

BACKGROUND: Kinase domain mutations in BCR-ABL1 are associated with resistance to tyrosine kinase inhibitors in patients with chronic myeloid leukaemia. Next-generation sequencing (NGS) allows detection of low-level kinase domain mutations, but its relevance in clinical practice remains debated. We aimed to examine the clinical effects of low-level kinase domain mutations identified using NGS in patients with chronic myeloid leukaemia. METHODS: In this population-based study, we included consecutive patients newly diagnosed with chronic myeloid leukaemia treated with first-line tyrosine kinase inhibitors, and patients identified at the time of resistance to first-line treatment with imatinib at six institutions (teaching hospitals and district hospitals) in southeast England. We screened patients for BCR-ABL1 kinase domain mutations using NGS, irrespective of patient response to tyrosine kinase inhibitor therapy. When we detected a mutation with NGS, we retrospectively analysed all previous samples to establish the date of first occurrence and subsequent kinetics of the mutant subclone (or subclones). The primary endpoints of this study were progression-free and event-free survival at 5 years. FINDINGS: Between Feb 1, 2007, and Dec 31, 2014, we screened 121 patients with chronic myeloid leukaemia for BCR-ABL1 kinase domain mutation. 99 consecutive patients were newly diagnosed, with available sequential RNA stored. The remaining 22 patients were diagnosed between June 1, 1999, and June 30, 2006, and were screened at the time of resistance to first-line treatment with imatinib. Imatinib was the first-line treatment for 111 patients, nilotinib for seven patients, and dasatinib for three patients. We detected a kinase domain mutation in 25 (21%) of 121 patients. Low-level kinase domain mutations were first identified in 17 (68%) of 25 patients with mutation. For patients with a complete cytogenetic response, 13 (14%) of 93 patients screened had a mutation. Five (71%) of the seven patients with a clinically relevant mutation lost complete cytogenetic response compared with 15 (17%) of 86 patients without a clinically relevant mutation (80 patients without mutation and six patients with a tyrosine kinase inhibitor-sensitive mutation, p=0·0031). Patients harbouring a mutant clone had poorer 5-year progression-free survival (65·3% [95% CI 40·5-81·8] vs 86·9% [75·8-93·2]; p=0·0161) and poorer 5-year event-free survival (22·2% [CI 5·6-45·9] vs 62·0% [50·4-71·6]; p<0·0001) than did patients without a mutation. We identified a kinase domain mutation in four (10%) of 41 patients with samples available at 3 months after starting first-line tyrosine kinase inhibitor treatment; all four subsequently progressed to accelerated phase disease compared with only three (8%) of 37 without a mutation (p<0·0001). INTERPRETATION: NGS reliably and consistently detected early appearance of kinase domain mutations that would not otherwise be detected by Sanger sequencing. For the first time, to our knowledge, we report the presence of kinase domain mutations after only 3 months of therapy, which could have substantial clinical implications. NGS will allow early clinical intervention and our findings will contribute to the establishment of new recommendations on the frequency of kinase domain mutation analysis to improve patient clinical care. FUNDING: None.

Similarities in lindane induced alteration in cytochrome P450s and associated signaling events in peripheral blood lymphocytes and brain.

Studies were initiated to investigate the similarities in alterations in cytochrome P450s (CYPs) and associated signaling events in brain and peripheral blood lymphocytes (PBL) induced by lindane, an organochlorine pesticide. Adult male albino wistar rats were treated orally with different doses (2.5- or 5.0- or 10- or 15 mg/kg/body weight) of lindane daily for 4 days. In another experiment, the treatment of low dose (2.5mg/kg) of lindane was continued for 15- and 21 days. A dose- and time-dependent increase was observed in the activity of CYP dependent enzymes in brain microsomes and PBL isolated from the treated rats. However, the magnitude of induction was several folds less in PBL. As observed in brain, RT-PCR and Western immunoblotting demonstrated that increase in CYP enzymes in PBL is due to the increase in the mRNA expression of specific CYP isoenzymes. Similarities were also observed in activation of ERK and JNK MAP kinases and c-jun in PBL or brain isolated from rats treated with lindane. Similarities in the induction of CYPs and activation of MAP kinases in PBL and brain suggest that CYP expression profiles in PBL could be used for monitoring the exposure and toxicity of environmental chemicals.

Induction of blood lymphocyte cytochrome P450 2E1 in early stage alcoholic liver cirrhosis.

To validate the induction of blood lymphocyte cytochrome P450 2E1 (CYP2E1) expression in alcoholic liver cirrhosis and mRNA and protein expression of CYP2E1 in freshly prepared blood lymphocytes of alcoholic liver cirrhotic (ACP), nonalcoholic cirrhotic patients (NACP), alcoholic controls (ACs), and nonalcoholic controls (NACs) were investigated. Registered ACP and NACP patients at Sanjay Gandhi Postgraduate Institute of Medical Science, Lucknow, India along with NACs and ACs were included in the study. Real time polymerase chain reaction, enzyme-linked immunosorbent assay, and CYP2E1-dependent enzyme activity were determined in blood lymphocytes isolated from cases and controls. Significant increases in CYP2E1 mRNA and protein expression were observed in freshly prepared blood lymphocytes isolated from ACs and ACP patients as compared with respective NACs or NACP patients. A concomitant increase in N-nitrosodimethyamine demethylase activity was evident in the blood lymphocytes of ACs and ACP patients. Interestingly, the comparative increase observed in CYP2E1 expression was of greater magnitude in the blood lymphocytes isolated from ACP patients, although they abstained from alcohol drinking. Findings suggest that significant increase in the CYP2E1 mRNA and protein expression in the blood lymphocytes, isolated from early stage ACP patients, can be used to predict alcohol-induced toxicity.

Association of polymorphism in alcohol dehydrogenase and interaction with other genetic risk factors with alcoholic liver cirrhosis.

The association of polymorphism of alcohol dehydrogenase (ADH) and its interaction with genes involved in the generation and detoxification of free radicals such as cytochrome P4502E1 (CYP2E1) and glutathione S-transferases M1 (GSTM1) were studied with alcoholic liver cirrhosis. The study included 175 alcoholic cirrhotic patients, 140 non-alcoholic cirrhotic patients, 255 non-alcoholic controls and 140 alcoholic controls. Our data revealed that the ADH1C*1/*1 genotype exhibited significant association with alcoholic liver cirrhosis while ADH1B genotypes did not show any significant association. A much higher risk to alcoholic liver cirrhosis was observed in patients carrying a combination of wild genotypes of ADH1C (ADH1C*1/*1) and variant genotype of ADH1B (ADH1B*2/*2) or CYP2E1 (CYP2E1*5B) or null genotype of GSTM1. Our data suggest a role for the interaction amongst the genes involved in metabolizing alcohol and in generating and detoxifying free radicals with susceptibility to alcoholic liver cirrhosis.

Polymorphism in glutathione-S-transferases: a risk factor in alcoholic liver cirrhosis.

In a case-control study, association of polymorphism in glutathione-S-transferases (GSTM1, GSTT1, GSTP1), involved in detoxification of reactive oxygen species (ROS), was studied with alcoholic liver cirrhosis. The study included 175 alcoholic cirrhotic patients (ACPs), 140 non-alcoholic cirrhotic patients (NACPs), visiting Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGI), Lucknow, India, 255 non-alcoholic controls and 140 alcoholic controls. The data showed an increase in risk to alcoholic cirrhosis in ACPs with GSTM1 (null) genotype when compared with non-alcoholic controls (OR: 1.7; 95% CI: 1.15-2.56) or alcoholic controls (OR: 1.7; 95% CI: 1.07-2.73). Significant increase in risk was also observed in ACPs with variant genotype of GSTP1 when compared with non-alcoholic controls (OR: 1.65; 95% CI: 1.12-2.43). A much higher risk to alcoholic liver cirrhosis was observed in patients carrying combination of null genotypes of GSTM1 and GSTT1 (OR: 2.8; 95% CI: 1.3-6.06) or variant genotype of GSTP1 and null genotype of GSTM1 (OR: 2.8; 95% CI: 1.58-4.90) or GSTT1 (OR: 2.16; 95% CI: 1.08-4.28). Likewise, greater risk for alcoholic cirrhosis was observed in patients carrying combination of GSTM1, GSTT1 (null) and variant genotype of GSTP1 (OR: 5.8; 95% CI: 2.17-15.80). Our data further showed that interaction of GSTs with variant genotype of manganese superoxide dismutase (MnSOD), which detoxifies free radicals, or cytochrome P450 2E1, which generates free radicals, resulted in several fold increase in risk to alcoholic liver cirrhosis in ACPs when compared with non-alcoholic controls thus demonstrating the role of gene-gene interactions in modulating the risk to alcoholic liver cirrhosis.

Cytochrome P450 2E1 and head and neck cancer: interaction with genetic and environmental risk factors.

The present case-control study investigates the association of polymorphisms in cytochrome P450 2E1 (CYP2E1), involved in the metabolism of tobacco carcinogens and alcohol, with Head and Neck Squamous Cell Carcinoma (HNSCC). In addition, the interaction of CYP2E1 (CYP2E1*5B and CYP2E1*6) with other genetic factors (null genotype of glutathione-S-Transferase M1, GSTM1, X-Ray Repair Cross Complementing Group I, XRCC1 (Arg194Trp), and environmental risk factors such as alcohol and tobacco in modifying HNSCC risk were investigated. Genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in a total of 350 male cases of HNSCC and an equal number of healthy male controls. Statistical analysis showed a significant increase in HNSCC risk in cases with variant genotypes of CYP2E1*5B (RsaI) (O.R. 3.44; 95% C.I. 1.45-8.14) and CYP2E1*6 (DraI) (O.R. 1.76; 95% C.I. 1.28-2.41). Haplotype analysis revealed that haplotype T-A was associated with a greater than 10-fold increase in risk for HNSCC. Our data also revealed a several fold increase in HNSCC risk in cases carrying a combination of variant genotypes of CYP2E1 with the null genotype of GSTM1 or XRCC1 variant genotypes. Alcohol or tobacco use (both smoking and chewing) were also found to interact with variant genotypes of CYP2E1 in significantly enhancing HNSCC risk. This increase in risk associated with an interaction of CYP2E1 genotypes with GSTM1 or XRCC1 or with tobacco and alcohol use demonstrates the importance of gene-gene and gene-environment interactions in the development of HNSCC.