Polypharmacological repurposing approach identifies approved drugs as potential inhibitors of Mycobacterium tuberculosis.

Mycobacterium tuberculosis (M. tb), the causative pathogen of tuberculosis (TB) remains the leading cause of death from single infectious agent. Furthermore, its evolution to multi-drug resistant (MDR) and extremely drug-resistant (XDR) strains necessitate de novo identification of drug-targets/candidates or to repurpose existing drugs against known targets through drug repurposing. Repurposing of drugs has gained traction recently where orphan drugs are exploited for new indications. In the current study, we have combined drug repurposing with polypharmacological targeting approach to modulate structure-function of multiple proteins in M. tb. Based on previously established essentiality of genes in M. tb, four proteins implicated in acceleration of protein folding (PpiB), chaperone assisted protein folding (MoxR1), microbial replication (RipA) and host immune modulation (S-adenosyl dependent methyltransferase, sMTase) were selected. Genetic diversity analyses in target proteins showed accumulation of mutations outside respective substrate/drug binding sites. Using a composite receptor-template based screening method followed by molecular dynamics simulations, we have identified potential candidates from FDA approved drugs database; Anidulafungin (anti-fungal), Azilsartan (anti-hypertensive) and Degarelix (anti-cancer). Isothermal titration calorimetric analyses showed that the drugs can bind with high affinity to target proteins and interfere with known protein-protein interaction of MoxR1 and RipA. Cell based inhibitory assays of these drugs against M. tb (H37Ra) culture indicates their potential to interfere with pathogen growth and replication. Topographic assessment of drug-treated bacteria showed induction of morphological aberrations in M. tb. The approved candidates may also serve as scaffolds for optimization to future anti-mycobacterial agents which can target MDR strains of M. tb.

Effects of Exercise Training in Patients with Lung Cancer during Chemotherapy Treatment.

Background: Cancer is the second greatest cause of death and disability after cardiovascular disease. Objective: To determine the effects of exercise training in patients with lung cancer during chemotherapy treatment. Methods: A randomised clinical trial was conducted in Shaukat Khanum Memorial Cancer Hospital and Institute of Radiotherapy and Nuclear Medicine (IRNUM) Peshawar. A total of 40 participants were randomly divided into two groups: i) the Experimental group (EG, n = 20) and ii) Control group (CG, n = 20). Both groups received exercise training for 4 weeks, with five sessions per week. The EG received pulmonary rehabilitation and aerobic training. The CG received only pulmonary rehabilitation. Both groups were evaluated at baseline and after 6 weeks through Mindful Attention Awareness Scale (MAAS) Urdu version, Six Minute Walk Test (6MWT), digital spirometry, Borgs scale, Hospital Anxiety and Depression Scale (HADs) and Visual Analogue Scale (VAS). Results: Both the EG and CG showed significant improvement in MAAS scores at post-study with a (P < 0.001). The scores of 6MWT were improved significantly in both groups after intervention with a (P = 0.001). The patient's anxiety scores were significantly improved in both groups after intervention with a (P < 0.001), while depression scores were also improved considerably between the two groups at post-level with a (P < 0.001). Regarding spirometry value, both groups showed significant improvement after intervention for forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC (P < 0.001). Both groups show significant differences in patient pain intensity and dyspnea at post-level with P < 0.001. Conclusion: This study concluded that pulmonary rehabilitation along with aerobic training can be more effective than pulmonary rehabilitation alone for patients with lung cancer during chemotherapy treatment.

Assessment of gingival thickness using digital file superimposition versus direct clinical measurements.

OBJECTIVES: This study was aimed at evaluating the correlation and reproducibility of gingival thickness quantification using digital and direct clinical assessment methods. MATERIALS AND METHODS: Patients in need of tooth extraction were allocated into two groups according to the gingival thickness measurement method, either using an endodontic spreader (pre-extraction) or a spring caliper (post-extraction), both on the mid-facial (FGT) and mid-lingual (LGT). Pre-extraction Digital Imaging and COmmunications in Medicine (DICOM) and STereoLithography (STL) files of the arch of interest were obtained and merged for corresponding digital measurements. Inter-rater reliability between digital and direct assessment methods was analyzed using inter-class correlation coefficients (ICC). RESULTS: Excellent inter-rater reliability agreement was demonstrated for all parameters. Comparison between the endodontic spreader and the digital method revealed excellent agreement, with ICC of 0.79 (95% CI 0.55, 0.91) for FGT and 0.87 (95% CI 0.69, 0.94) for LGT, and mean differences of 0.08 (- 0.04 to 0.55) and 0.25 (- 0.30 to 0.81) mm for FGT and LGT, respectively. Meanwhile, the comparison between the caliper and the digital method demonstrated poor agreement, with ICC of 0.38 (95% CI - 0.06, 0.70) for FGT and 0.45 (95% CI - 0.02, 0.74) for LGT, and mean differences of 0.65 (0.14 to 1.16) and 0.64 (0.12 to 1.17) mm for FGT and LGT, respectively. CONCLUSIONS: Digital measurement of gingival thickness is comparable with direct clinical assessments performed with transgingival horizontal probing using an endodontic spreader. CLINICAL RELEVANCE: Digital assessment of gingival thickness is a non-tissue invasive, reliable, and reproducible method that could be utilized as an alternative to horizontal transgingival probing.

Clinical Practice Guidelines For The Management Of Colorectal Cancer, A Consensus Statement By The Society Of Surgeons® And Surgical Oncology Society Of Pakistan®.

A joint effort by the Society of Surgeons Pakistan and Society of Surgical Oncology Pakistan, these guidelines provide a framework for the practicing surgeons involved in care and management of patients with colorectal cancer. The guidelines take into account the issues related to our local circumstances and provide a minimum standard of care that must be given to these patients. The Guideline Committee had members from all disciplines, including surgery, surgical oncology, medical oncology and radiation oncology. The guidelines have attempted to simplify things to understand and follow for the practicing surgeons. With these guidelines we wish to eliminate disparities in treatment among institutions and prevent any under treatment of patients.

rs2651899 variant is associated with risk for migraine without aura from North Indian population.

Recently a GWAS study had identified 38 genomic variants commonly found in humans that influence migraine risk. For further replicate these findings, we selected two SNPs; rs2651899 on chromosome 1p36.32 in PRDM16 gene and rs10166942 on chromosome 2q37.1 close to TRPM8 gene for their associations with migraine in the North Indian population as much work has not been done on these variants before from this population. In this case-control association study, 300 unrelated subjects, including 150 migraineurs (43 migraine with aura and 107 migraine without aura) and 150 healthy controls were selected to collect genomic DNA. Polymerase chain reaction and restriction-fragment-length polymorphism methods were performed for genotyping of these variants. Univariate and multivariate analyses were done to find the association of different genotypes and alleles of these SNPs with migraine and its subgroups. We found a statistically significant difference in migraineurs with control for PRDM16 rs2651899 polymorphism at genotypic (p < 0.05), allelic (p = 0.022; OR 1.462; 95% CI 1.058-2.022) and for dominant model (p = 0.011; OR 1.957; 95% CI 1.169-3.276). A similar trend was observed both on subgroup and gender analysis in migraine without aura (MO) and females respectively for rs2651899 variant. For the other SNP (rs10166942), statistically non-significant differences were reported in the allelic/genotypic frequencies between migraineurs and controls as p > 0.05. However, on subgroup analysis we found statistically significant differences at genotypic (p < 0.05) and dominant models in migraine with aura (MA) and in males with that of entire controls. But no significant association was found at allelic level in both subgroup and gender analysis for rs10166942. This research study showed that rs2651899 is a potential genetic marker for migraine susceptibility in MO and female subgroup at both genotypic and allelic level in the North Indian population and found that rs10166942 variant may be a potential marker for MA and male subgroup. Further work with large sample size is required for these SNPs to understand their functional mechanisms and to strengthen our results.

Transformation of heavy metals from contaminated water to soil, fodder and animals.

A serious environmental problem that threatens soil quality, agricultural productivity, and food safety is heavy metal pollution in water sources. Heavy metal pollution is the main problem in tehsil Pasrur, Sialkot, Pakistan. Present study was arranged to notice the heavy metals in water, soil, forages and buffalo milk. There are seven sites that were used for this experiment. Highest malondialdehyde (MDA) contents (3.00 ± 0.01) were noticed in barseem roots at site 7. Ascorbate Peroxidase (APX) was reached at its peak (1.93 ± 0.01) at site 7 in the fresh barseem. Maximum protein contents (0.36 ± 0.01) were observed in fresh plant samples at site 2. Site 3's buffalo milk samples had the highest Ni content (7.22 ± 0.33 ppm), while Site 3's soil samples had the lowest Cr content (8.89 ± 0.56 ppm), Site 1's plant shoots had the lowest Cr content (27.75 ± 1.98 ppm), and Site 3's water had the highest Cr content (40.07 ± 0.49 ppm). The maximum fat content (5.38 ± 2.32%) was found in the milk of the animals at site 7. The highest density (31.88 ± 6.501%), protein content (3.64 ± 0.33%), lactose content (5.54 ± 0.320%), salt content (0.66 ± 0.1673%), and freezing point (- 0.5814 ± 0.1827 °C) were also observed in the milk from animals at site 7, whereas site 5 displayed the highest water content (0.66 ± 0.1673%) and peak pH value (11.64 ± 0.09). In selected samples, the pollution load index for Ni (which ranged from 0.01 to 1.03 mg/kg) was greater than 1. Site 7 has the highest conductivity value (5.48 ± 0.48). Values for the health risk index varied from 0.000151 to 1.00010 mg/kg, suggesting that eating tainted animal feed may pose health concerns. Significant health concerns arise from metal deposition in the food chain from soil to feed, with nickel having the highest health risk index.

Double Stab Excision Arteriotomy-A Novel Technique For A Better Outcome.

BACKGROUND: This study was carried out to introduce a new technique of excision arteriotomy and to compare it with standard excision arteriotomy in terms of achieving desired size, shape and margins with minimal technical problems. METHODS: This was a comparative study carried out at the Vascular Surgery Unit of Combined Military Hospital Peshawar between January and September 2022. A total of 150 patients of chronic renal failure undergoing Arteriovenous access fulfilling the inclusion criteria were enrolled in our study. The patients were randomized into two groups, 75 in each group: Group A consisted of patients who underwent Conventional excision arteriotomy and Group B underwent Double Stab excision Arteriotomy. The endpoint of the study was to achieve an appropriate arteriotomy of the desired size and shape by having regular margins without intimal dissection during its formation or otherwise inappropriate arteriotomy if any of the criteria is not met. RESULTS: Among the total 150 patients included in our study, Ages ranged between 30-60 years and a mean age of 52.5 years. There were 82 (54.66%) males and 68 (45.33%) females with a male-to-female ratio of 1.2:1. In group A (Conventional Excision arteriotomy) there were 30 (40%) inappropriate arteriotomies and 45 (60%) appropriate arteriotomies. Among the total 30(40%) inappropriate arteriotomies in group A, larger than desired size arteriotomies were 10 cases (33.33%) followed by smaller than desired size arteriotomies; 6 (20%), irregular margins 9 (30%), intimal dissection 3(10%) & lateral tear 2 (6.66%) respectively. In group B of double stab excision arteriotomies, appropriate arteriotomies were achieved in 69 (92%) while the rest had inappropriate arteriotomies in 6 (8%). Among the total 6 (8%) inappropriate arteriotomies in group B, larger than desired size arteriotomies were 2 (33.33%), smaller than desired size arteriotomy; 1 (16.66%), irregular margins 1 (16.66%), intimal dissection;2 (33.33%) & no lateral tear respectively. CONCLUSIONS: This study concluded that the Double stab excision arteriotomy technique is superior to the conventional excision arteriotomy technique. The advantages of our technique are; its reliability with a short learning curve and can be performed precisely and safely.

A Retrospective Follow-Up Study To Show The Effectiveness Of Booster Dose Of Foam Sclerotherapy Session At 3rd And 6th Months In Preventing The Recurrence Of Varicose Veins.

BACKGROUND: Injection sclerotherapy administration is known to cause a decreased recurrence of varicose vein disease. This research aimed to investigate the recurrence of varicose vein disease after giving booster doses of injection sclerotherapy. The booster doses were given at 3rd and 6th months. METHODS: One hundred and fifty patients participated and all patient's included ages 30-70 in the category of 'low risk' patients. The patients were both males and females. Patients participating in the study were counselled appropriately and written consent was taken from them. Moreover, the patients selected were volunteers and agreed to be part of the study. Patients who were above 70 years of age, those who were at a high-risk due to some co-morbidities (high-risk patients), patients not willing to be part of the study, those allergic to drugs being used including sclerosant and people with any known psychiatric illness or cardiac arrhythmias, deep venous thrombosis patients, patients having arteriovenous malformation/venous ulcers were all excluded. If the patient was pregnant, the gynaecology team was taken on board and the procedure was carried out. Every procedure was carried out under the direct supervision of the supervisor. Booster dose sessions of Foam Sclerotherapy were held at 3rd and 6th months of the study time. Their effectiveness was observed and documentation was carried out. RESULTS: Since it was a procedure that could be done in the OPD, there was no need for specialized anaesthesia care. It is of significant notice that when a patient of varicose veins was given a booster intravenous sclerosant injection at 3rd and 6th month of treatment, chances of recurrence decreased to 50%.

The exploitation of host autophagy and ubiquitin machinery by Mycobacterium tuberculosis in shaping immune responses and host defense during infection.

Intracellular pathogens have evolved various efficient molecular armaments to subvert innate defenses. Cellular ubiquitination, a normal physiological process to maintain homeostasis, is emerging one such exploited mechanism. Ubiquitin (Ub), a small protein modifier, is conjugated to diverse protein substrates to regulate many functions. Structurally diverse linkages of poly-Ub to target proteins allow enormous functional diversity with specificity being governed by evolutionarily conserved enzymes (E3-Ub ligases). The Ub-binding domain (UBD) and LC3-interacting region (LIR) are critical features of macroautophagy/autophagy receptors that recognize Ub-conjugated on protein substrates. Emerging evidence suggests that E3-Ub ligases unexpectedly protect against intracellular pathogens by tagging poly-Ub on their surfaces and targeting them to phagophores. Two E3-Ub ligases, PRKN and SMURF1, provide immunity against Mycobacterium tuberculosis (M. tb). Both enzymes conjugate K63 and K48-linked poly-Ub to M. tb for successful delivery to phagophores. Intriguingly, M. tb exploits virulence factors to effectively dampen host-directed autophagy utilizing diverse mechanisms. Autophagy receptors contain LIR-motifs that interact with conserved Atg8-family proteins to modulate phagophore biogenesis and fusion to the lysosome. Intracellular pathogens have evolved a vast repertoire of virulence effectors to subdue host-immunity via hijacking the host ubiquitination process. This review highlights the xenophagy-mediated clearance of M. tb involving host E3-Ub ligases and counter-strategy of autophagy inhibition by M. tb using virulence factors. The role of Ub-binding receptors and their mode of autophagy regulation is also explained. We also discuss the co-opting and utilization of the host Ub system by M. tb for its survival and virulence.Abbreviations: APC: anaphase promoting complex/cyclosome; ATG5: autophagy related 5; BCG: bacille Calmette-Guerin; C2: Ca2+-binding motif; CALCOCO2: calcium binding and coiled-coil domain 2; CUE: coupling of ubiquitin conjugation to ER degradation domains; DUB: deubiquitinating enzyme; GABARAP: GABA type A receptor-associated protein; HECT: homologous to the E6-AP carboxyl terminus; IBR: in-between-ring fingers; IFN: interferon; IL1B: interleukin 1 beta; KEAP1: kelch like ECH associated protein 1; LAMP1: lysosomal associated membrane protein 1; LGALS: galectin; LIR: LC3-interacting region; MAPK11/p38: mitogen-activated protein kinase 11; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAP3K7/TAK1: mitogen-activated protein kinase kinase kinase 7; MAPK8/JNK: mitogen-activated protein kinase 8; MHC-II: major histocompatibility complex-II; MTOR: mechanistic target of rapamycin kinase; NBR1: NBR1 autophagy cargo receptor; NFKB1/p50: nuclear factor kappa B subunit 1; OPTN: optineurin; PB1: phox and bem 1; PE/PPE: proline-glutamic acid/proline-proline-glutamic acid; PknG: serine/threonine-protein kinase PknG; PRKN: parkin RBR E3 ubiquitin protein ligase; RBR: RING-in between RING; RING: really interesting new gene; RNF166: RING finger protein 166; ROS: reactive oxygen species; SMURF1: SMAD specific E3 ubiquitin protein ligase 1; SQSTM1: sequestosome 1; STING1: stimulator of interferon response cGAMP interactor 1; TAX1BP1: Tax1 binding protein 1; TBK1: TANK binding kinase 1; TNF: tumor necrosis factor; TRAF6: TNF receptor associated factor 6; Ub: ubiquitin; UBA: ubiquitin-associated; UBAN: ubiquitin-binding domain in ABIN proteins and NEMO; UBD: ubiquitin-binding domain; UBL: ubiquitin-like; ULK1: unc-51 like autophagy activating kinase 1.

A review on properties, challenges and commercial aspects of eco-friendly biolubricants productions.

Lubricants operate as antifriction media, preserving machine reliability, facilitating smooth operation, and reducing the likelihood of frequent breakdowns. The petroleum-based reserves are decreasing globally, leading to price increases and raising concerns about environmental degradation. The researchers are concentrating their efforts on developing and commercializing an environmentally friendly lubricant produced from renewable resources. Biolubricants derived from nonedible vegetable oils are environmentally favorable because of their non-toxicity, biodegradability, and close to net zero greenhouse gas emissions. The demand for bio lubricants in industry and other sectors is increasing due to their non-toxic, renewable, and environmentally friendly nature. Good lubrication, anti-corrosion, and high flammability are characteristic properties of vegetable oils due to their unique structure. This study presents several key properties of nonedible oils that are used to produce lubricants via the transesterification process. Bibliometric analysis is also performed, which provides us with a better understanding of previous studies related to the production of bio lubricants from the transesterification process. Only 371 published documents in the Scopus database were found to relate to the production of bio lubricants using the transesterification process. The published work was mostly dominated by research articles (286; 77.088%). Significant development can be seen in recent years, with the highest occurrence in 2021, reaching 68 publications accounting for 18.38% of the total documents. In the second step, (i) the authors with the most number of publications; (ii) journals with the most productions; (iii) most productive countries; and (iv) the authors' most frequently used keywords were evaluated. These results will provide a pathway for researchers interested in this field. Lastly, recommendation is made on research gaps to device possible strategies for its commercialization.

Treatment Outcomes Of Patients With Hairy Cell Leukaemia; A 16-Year Experience At A Tertiary Care Center In Pakistan.

BACKGROUND: Hairy cell leukaemia (HCL) is an uncommon neoplasm of mature B-lymphoid cells which is characterized by cytopenias, commonly of all three cell lines, with typical hairy cells on peripheral smear and/or bone marrow along with organomegaly. Objective was to document the outcomes of HCL patients treated at a tertiary care hospital in Pakistan. METHODS: Medical records of patients from 2004 to 2020 were reviewed and data was collected to assess patient's demographics, symptomatology, remission rate and overall survival. The record flies of all patients presenting to AFBMTC with HCL were included in the study. The record file with insufficient data were excluded. RESULTS: 26 patients with a mean age of 48.12±11.43 years were diagnosed with HCL and treated at AFBMTC. Out of these, 23 (88.4%) were male and 03 (11.5%) females. The main presenting complaints were generalized body aches (34.6%), fever (15.4%), incidental finding of cytopenias (11.5%) and abdominal discomfort (26.9%). Splenomegaly was found in 76.92% while hepatomegaly was found in 46.15% of patients. A total of 12 (46.15%) patients received Cladribine (either intravenous or subcutaneous) and splenectomy was done in 7 (26.92%) as 1st line treatment. Eleven patients out of 12 (83.33%) who received Cladribine and 05 (71.42%) patients out of seven who underwent splenectomy; achieved complete remission (CR) after 1 st line of treatment. One patient received Cladribine as 1st line of treatment but did not respond and CHOP regimen was given as second line. Out of the 26 patients, 5 patients (19.23%) relapsed at a median interval of 5.83±6.6 years. Two patients received Cladribine + Rituximab while 03 patients received cladribine as their salvage therapy. Disease free survival (DFS) of 71.4% among the patients underwent splenectomy while 75.0% among the patients received Cladribine. DFS for combination therapy (included CHOP and CVP) was 66.7% while OS was calculated among patients who received cladribine, splenectomy and combination chemotherapy as 100%, 85.7%, 66.7% respectively. CONCLUSIONS: Cladribine has a significant efficacy and encouraging acute and long-term benefits when administered to patients with HCL. A single course of cladribine was able to induce CR in a vast majority of patients. At a median follow up of 4.6 years the OS was 100% with cladribine and 85% with splenectomy. Those who relapsed were successfully retreated with cladribine + Rituximab.

Characterization of Extraction Sockets by Indirect Digital Root Analysis.

This study aimed to characterize extraction sockets based on indirect digital root analysis. The outcomes of interest were estimated socket volume and dimensions of the socket orifice. A total of 420 extracted teeth, constituting 15 complete sets of permanent teeth (except third molars), were selected. Teeth were scanned to obtain STL files of the root complex for digital analysis. After digitally sectioning each root 2.0 mm apical to the cementoenamel junction (CEJ), root volume was measured in mm3 and converted to cc. Subsequently, a horizontal section plane was drawn at the most zenithal level of the buccal CEJ, and the surface area (in mm2) and buccolingual and mesiodistal linear measurements of the socket orifice (in mm) were computed. Maxillary first molars exhibited the largest mean root volume (0.451 ± 0.096 cc) and mandibular central incisors the smallest (0.106 ± 0.02 cc). Surface area analysis demonstrated that mandibular first molars presented the largest socket orifice area (78.56 ± 10.44 mm2), with mandibular central incisors presenting the smallest area (17.45 ± 1.82 mm2). Maxillary first molars showed the largest mean socket orifice buccolingual dimension (11.08 ± 0.60 mm), and mandibular first molars showed the largest mean mesiodistal dimension (9.73 ± 0.84 mm). Mandibular central incisors exhibited the smallest mean buccolingual (5.87 ± 0.26 mm) and mesiodistal (3.52 ± 0.24 mm) linear dimensions. Findings from this study can be used by clinicians to efficiently plan extraction-site management procedures (such as alveolar ridge preservation via socket grafting and sealing) and implant provisionalization therapy, and by the industry to design products that facilitate site-specific execution of these interventions.

Stray bullet in inferior vena cava.

A young boy presented in emergency with history of being hit by a stray bullet injuring the right hypochondrium. Ultrasound of abdomen showed hemoperitoneum and the radiograph showed bullet in the pelvis. Exploratory laparotomy showed injuries to liver and cystic duct with tract leading retroperitoneally into the inferior vena cava. The bullet was found wandering inside the vena caval lumen. Stray bullets are presumed to remain limited to the soft tissues. However, the trajectory, impact velocity and the involved region ultimately determine the outcome and influence management.

Comparative study of ultrasound guided fine needle aspiration cytology with open/laparoscopic biopsy for diagnosis of carcinoma gallbladder.

OBJECTIVE: To determine the accuracy of Fine Needle Aspiration Cytology (FNAC) in cases of gallbladder mass. STUDY DESIGN: Comparative study. PLACE AND DURATION OF STUDY: Surgical Units of Mayo Hospital, Lahore and Lahore General Hospital, Lahore in collaboration with the Department of Radiology, Sir Ganga Ram Hospital, Lahore and Department of Pathology of PGMI, Lahore, from September 2006 to September 2007. METHODOLOGY: Ultrasound guided fine needle aspiration cytology was done in all cases and histopathological findings were confirmed with open/laparoscopic biopsies. The results of these two modalities were compared. RESULTS: Fifty cases with mean age 60.71+11.073 years presented with mass gallbladder underwent FNAC. Smears showed adenocarcinoma 23, undifferentiated carcinoma in 7, dysplasia and suspicion of malignancy in 5, hemorrhagic background without malignant cells in 12 and inflammatory cells with no malignancy in 3 cases. Results compared with open/ laparoscopic biopsy showed a sensitivity, specificity and Positive Predictive Value (PPV) of 72.91%, 100% and 100% respectively. CONCLUSION: Ultrasound guided FNAC is a safe and less invasive diagnostic modality for diagnosing carcinoma gall bladder preventing the patient to undergo major surgery and helps in better quality of life.

Transhiatal esophageal surgery for malignancy--a 7-year experience at a tertiary care hospital.

OBJECTIVE: The aim of this study was to determine the outcomes of transhiatal esophagectomy for dysphagia for esophageal malignancy in terms of short and long-term morbidity and mortality and to determine the survival series. STUDY DESIGN: Case series study. PLACE AND DURATION OF STUDY: South and West Surgical Ward, Mayo Hospital, Lahore, from January 2001 to December 2007. METHODOLOGY: All patients referred electively or admitted through OPD presenting with features of progressive dysphagia due to malignancy were included in the study. The patients were investigated for site of stricture and extent of growth into the surrounding structures. All underwent transhiatal esophagectomy and gastric tube or colon was used as the conduit to restore continuity. Patients with squamous cell variety were referred to oncology department for chemoradiotherapy postoperatively. Morbidity and in-hospital mortality were recorded. RESULTS: A total of 42 patients were operated electively for malignant stricture esophagus through transhiatal approach. Site of lesion were 5 (11.9%) upper, 13 (31%) middle and 24 (58%) at lower end of esophagus. The TNM staging were stage I, IIa, IIb, III and IV in zero (0), 5 (11%), 10 (22%), 24 (57.8%) and 3 (7.1%) respectively. Mean operating time was 154 minutes and average blood loss of 371 ml. Postoperative complications included pneumothorax 16.7%, pulmonary complication (16.7%), anastomotic leakage (9.5%), wound infection (3.4%), recurrent laryngeal nerve injury (4.8%) and stricture formation (4.8%). Only 3 (7.1%) 30-day in-hospital mortality was recorded. CONCLUSION: Transhiatal esophagectomy is the surgical treatment of choice for resection of carcinoma esophagus specifically at the lower and mid-esophageal levels. The frequency of complications is lower as compared to transthoracic approach and the early stage of presentation can lead to high 5-year survival ratios.

Could rs4379368 be a genetic marker for North Indian migraine patients with aura?: Preliminary evidence by a replication study.

BACKGROUND: Genome wide association studies (GWAS) have already found different migraine single nucleotide polymorphisms (SNPs). To further check if these variants differ by ethnicity, three single nucleotide polymorphisms (SNPs) (rs4379368, rs10504861and rs11172113) were genotyped here to find association with migraine susceptibility from North Indian population. METHODS AND RESULTS: A case control study in 200 subjects was done by polymerase chain reaction and restriction-fragment-length polymorphism (PCR-RFLP) analysis. Univariate analysis was performed to check the association of different genotypic and allelic frequencies of these variants with migraine and its subtypes. We could not find any statistically relevant differences among frequencies at various levels of these selected SNPs between patients and healthy controls in this study (p > 0.05). However on subgroup analysis for rs4379368 SNP, the CT genotype was higher in migraine with aura (MA) (69.6%) than migraine without aura (MO) (51.9%) or control (42%) (p < 0.05). But this relation was not significant at allelic level. For other two SNPs, statistically significant differences were not observed in any of the two migraine subgroups. CONCLUSIONS: This study was able to associate the role of rs4379368 SNP with migraine susceptibility and suggested that genotype CT in rs4379368 SNP could be a possible genetic marker for MA. More studies with larger sample size are needed to strengthen our results.

Using Telemedicine to Diagnose Surgical Site Infections in Low- and Middle-Income Countries: Systematic Review.

BACKGROUND: A high burden of preventable morbidity and mortality due to surgical site infections (SSIs) occurs in low- and middle-income countries (LMICs), and most of these SSIs occur following discharge. There is a high loss to follow-up due to a wide geographical spread of patients, and cost of travel can result in delayed and missed diagnoses. OBJECTIVE: This review analyzes the literature surrounding the use of telemedicine and assesses the feasibility of using mobile phone technology to both diagnose SSIs remotely in LMICs and to overcome social barriers. METHODS: A literature search was performed using Medline, Embase, CINAHL, PubMed, Web of Science, the Cochrane Central Register of Controlled Trials and Google Scholar. Included were English language papers reporting the use of telemedicine for detecting SSIs in comparison to the current practice of direct clinical diagnosis. Papers were excluded if infections were not due to surgical wounds, or if SSIs were not validated with in-person diagnosis. The primary outcome of this review was to review the feasibility of telemedicine for remote SSI detection. RESULTS: A total of 404 articles were screened and three studies were identified that reported on 2082 patients across three countries. All studies assessed the accuracy of remote diagnosis of SSIs using predetermined telephone questionnaires. In total, 44 SSIs were accurately detected using telemedicine and an additional 14 were picked up on clinical follow-up. CONCLUSIONS: The use of telemedicine has shown to be a feasible method in remote diagnosis of SSIs. Telemedicine is a useful adjunct for clinical practice in LMICs to decrease loss to postsurgical follow-up.

Swirl Sign - A C T Angiogram Alarm Sign or Congenital Trans-Mesenteric Hernias.

Congenital trans-mesenteric hernias (CTMHs) are caused by rent in the mesentry of bowel. The lesions commonly present in pediatric age group. Adult CTMHs usually present with complication of the problem. The diagnosis is often late and is associated with morbidity as well as mortality due to bowel ischemia. There is no specific sign associated with this condition. A case is reported of a patient diagnosed with CTMH on high suspicion by the radiologist based on her finding of abnormal swirling of superior mesenteric artery on CT angiogram. Swirl sign on CT angiogram warrants an early surgical consultation to prevent any morbidity.

Pregnant Lady With Undiagnosed Hodgkin's Disease Presenting As Secondary Sclerosing Cholangitis.

Hodgkin's lymphoma. A 25 years old lady, 34 weeks primigravida was referred from the Emergency Department to the Medical Unit Khyber Teaching Hospital-MTI, Peshawar with four weeks of fever, progressive jaundice, pruritus, night sweats and weight loss. LFTs showed cholestatic picture, ERCP showed scanty intrahepatic giving beading and autumn tree appearance typical of sclerosing cholangitis. CBD was normal. Doppler U/S of hepatic and portal vein reported normal. She was started on steroids, ursodeoxycholic acid and antibiotics 3rd generation cephalosporins to which she did not respond well. This prompted a Liver biopsy which showed Hodgkin's disease having mixed cellularity. She was shifted to specialized oncology unit for further management where she died of irreversible liver damage. This is a rare case of secondary sclerosing cholangitis in Hodgkin's lymphoma of liver and the first case reported to our Hospital.

Duodenal Perforation due to Ingested Partial Denture.

Ingestion of foreign bodies including dentures can be a cause of morbidity and mortality. We report a case of poor-fit denture in an elderly male with pulmonary and musculoskeletal comorbidities, who presented as an acute abdomen. The pin attached to the denture caused perforation of first part of duodenum. The only positive finding prior to surgery was a radiopaque density in the abdominal radiograph of the patient and air under the diaphragm. It is important for all the surgeons dealing with acute care patients to be aware of different designs and constructions of dentures.