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OBJECTIVE: To evaluate the role of postoperative antibiotics in reducing surgical site infections after appendectomy for non-perforated appendicitis. METHODS: The randomised controlled trial was conducted at Khyber Teaching Hospital, Peshawar, Pakistan, from November 11, 2012, to May 30, 2014, and comprised patients of emergency appendectomy for non-perforated appendicitis who were divided into groups A and B. Group A received a single dose of cefuroxime sodium and metronidazole half-an-hour before induction, while Group B received one more dose of the same antibiotics postoperatively. Both groups were followed for 6 weeks. SPSS 20 was used for statistical analysis. RESULTS: Of the 390 patients in the study, 192(49.2%) were in Group A and 198(50.7%) in Group B. Number of surgical site infections was 15(7.8%) in Group A and 18(9.1%) in Group B (p=0.65). Mean hospital stay of 3.32±0.4 days and 3.59±0.46 days was observed for Group A and B, respectively, (p<0.001). CONCLUSIONS: A single pre-operative dose of cefuroxime and metronidazole had the same efficacy in preventing surgical site infections in cases of non-perforated appendicitis as when the same regimen was repeated post-operatively.
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Antibacterianos/administração & dosagem , Antibioticoprofilaxia , Apendicectomia , Apendicite/terapia , Cefuroxima/administração & dosagem , Metronidazol/administração & dosagem , Cuidados Pós-Operatórios/métodos , Infecção da Ferida Cirúrgica/prevenção & controle , Adolescente , Adulto , Criança , Quimioterapia Combinada , Feminino , Humanos , Tempo de Internação , Masculino , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To determine the effectiveness of simple control measures on the infection status and characteristics of methicillin-resistant Staphylococcus aureus including susceptibility patterns among health professionals and patients in a teaching hospital. METHODS: The cross-sectional study was conducted from September 2013 to January 2014, and comprised samples collected from healthcare personnel and patients in the various units of Khyber Teaching Hospital, Peshawar. The specimens were collected before and one month after the implementation of simple control measures for outbreak prevention of methicillin-resistant Staphylococcus aureus. These were tested for culture and antimicrobial susceptibility. Data about methicillin-sensitive and methicillin-resistant Staphylococcus aureus infection, wound characteristics and susceptibility patterns was collected and effectiveness of simple control measures was determined. SPSS 20 was used for statistical analysis. RESULTS: Of the total 390 isolates, 180(46.2%) were Staphylococcus aureus; 77(19.7%) from healthcare personnel and 103(26.4%) from patients. Of these, 164(42.1%) were methicillin-sensitive and 16(4.1%) were methicillin-resistant. Among the patients, 38(15.1%) methicillin-sensitive and 8(3.2%) methicillin-resistant isolates were recovered from wounds or skin and soft tissues. Pus with 33(13.1%) and 4(1.6%) cases respectively was the second most common source. Among methicillin-resistant isolates, resistance to Linezolid was 0%, all were resistant to Oxacillin, Cefoxitin, Amoxicillin, Cefotaxime and Cephradine, and resistance to both Co-Amoxiclav and Ciprofloxacin was 87.5%. After one month of implementation of simple control measures, the number of methicillin-resistant cases among healthcare professionals and patients dropped from 4(2.9%) and 7(10.8%) to 1(0.7%) and 5(2.7%), respectively. CONCLUSIONS: Methicillin-resistant and methicillin-sensitive Staphylococcus aureus differed in their anti-microbial susceptibility profiles. Selection of antibiotics based on susceptibility and culture is needed for prevention of resistance and effective treatment. A decrease was observed in methicillin-resistant cases with implementation of control measures.
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Antibacterianos/uso terapêutico , Infecção Hospitalar/prevenção & controle , Controle de Infecções/métodos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/prevenção & controle , Estudos Transversais , Surtos de Doenças , Suscetibilidade a Doenças , Farmacorresistência Bacteriana , Hospitais de Ensino , Humanos , Incidência , Testes de Sensibilidade Microbiana , Paquistão/epidemiologia , Prevalência , Infecções Estafilocócicas/epidemiologiaRESUMO
Gene mutations are a source of genetic instability which fuels the progression of cancer. Mutations in BRCA1 and BRCA2 are considered as major drivers in the progression of breast cancer and their detection indispensable for devising therapeutic and management approaches. The current study aims to identify novel pathogenic and recurrent mutations in BRCA1 and BRCA2 in Pakhtun population from the Khyber Pakhtunkhwa. To determine the BRCA1 and BRCA2 pathogenic mutation prevalence in Pakhtun population from KP, whole exome sequencing of 19 patients along with 6 normal FFPE embedded blocks were performed. The pathogenicity of the mutations were determined and they were further correlated with different hormonal, sociogenetic and clinicopathological features. We obtained a total of 10 mutations (5 somatic and 5 germline) in BRCA1 while 27 mutations (24 somatic and 3 germline) for BRCA2. Five and seventeen pathogenic or deleterious mutations were identified in BRCA1 and BRCA2 respectively by examining the mutational spectrum through SIFT, PolyPhen-2 and Mutation Taster. Among the SNVs, BRCA1 p.P824L, BRCA2 p. P153Q, p.I180F, p.D559Y, p.G1529R, p.L1576F, p.E2229K were identified as mutations of the interaction sites as predicted by the deep algorithm based ISPRED-SEQ prediction tool. SAAFEQ-SEQ web-based algorithm was used to calculate the changes in free energy and effect of SNVs on protein stability. All SNVs were found to have a destabilizing effect on the protein. ConSurf database was used to determine the evolutionary conservation scores and nature of the mutated residues. Gromacs 4.5 was used for the molecular simulations. Ramachandran plots were generated using procheck server. STRING and GeneMania was used for prediction of the gene interactions. The highest number of mutations (BRCA1 7/10, 70 %) were on exon 9 and (BRCA2, 11/27; 40 %) were on exon 11. 40 % and 60 % of the BRCA2 mutations were associated Grade 2 and Grade 3 tumors respectively. The present study reveals unique BRCA1 and BRCA2 mutations in Pakhtun population. We further suggest sequencing of the large cohorts for further characterizing the pathogenic mutations.
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Proteína BRCA1 , Proteína BRCA2 , Neoplasias da Mama , Feminino , Humanos , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Etnicidade , Genes BRCA2 , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Mutação , Paquistão/epidemiologia , População do Sul da Ásia/genéticaRESUMO
In this study, we report the mutational profiles, pathogenicity, and their association with different clinicopathologic and sociogenetic factors in patients with Pashtun ethnicity for the first time. A total of 19 FFPE blocks of invasive ductal carcinoma (IDC) from the Breast Cancer (BC) tissue and 6 normal FFPE blocks were analyzed by whole-exome sequencing (WES). Various somatic and germline mutations were identified in cancer-related genes, i.e., ATM, CHEK2, PALB2, and XRCC2. Among a total of 18 mutations, 14 mutations were somatic and 4 were germline. The ATM gene exhibited the maximum number of mutations (11/18), followed by CHEK2 (3/18), PALB2 (3/18), and XRCC2 (1/18). Except one frameshift deletion, all other 17 mutations were nonsynonymous single-nucleotide variants (SNVs). SIFT prediction revealed 7/18 (38.8%) mutations as deleterious. PolyPhen-2 and MutationTaster identified 5/18 (27.7%) mutations as probably damaging and 10/18 (55.5%) mutations as disease-causing, respectively. Mutations like PALB2 p.Q559R (6/19; 31.5%), XRCC2 p.R188H (5/19; 26.31%), and ATM p.D1853N (4/19; 21.05%) were recurrent mutations and proposed to have a biomarker potential. The protein network prediction was performed using GeneMANIA and STRING. ISPRED-SEQ indicated three interaction site mutations which were further used for molecular dynamic simulation. An average increase in the radius of gyration was observed in all three mutated proteins revealing their perturbed folding behavior. Obtained SNVs were further correlated with various parameters related to the clinicopathological status of the tumors. Three mutation positions (ATM p. D1853N, CHEK2 p.M314I, and PALB2 p.T1029S) were found to be highly conserved. Finally, the wild- and mutant-type proteins were screened for two drugs: elagolix (DrugBank ID: DB11979) and LTS0102038 (a triterpenoid, isolated from the anticancer medicinal plant Fagonia indica). Comparatively, a higher number of interactions were noted for normal ATM with both compounds, as compared to mutants.
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Herein, we report the mutational spectrum of three breast cancer candidate genes (TP53, PIK3CA, and PTEN) using WES for identifying potential biomarkers. The WES data were thoroughly analyzed using SAMtools for variant calling and identification of the mutations. Various bioinformatic tools (SIFT, PolyPhen-2, Mutation Taster, ISPRED-SEQ, SAAFEQ-SEQ, ConSurf, PROCHECK etc.) were used to determine the pathogenicity and nature of the SNVs. Selected interaction site (IS) mutations were visualized in PyMOL after building 3D structures in Swiss-Model. Ramachandran plots were generated by using the PROCHECK server. The selected IS mutations were subjected to molecular dynamic simulation (MDS) studies using Gromacs 4.5. STRING and GeneMANIA were used for the prediction of gene-gene interactions and pathways. Our results revealed that the luminal A molecular subtype of the breast cancer was most common, whereas a high percentage of was Her2 negatives. Moreover, the somatic mutations were more common as compared to the germline mutations in TP53, PIK3CA, and PTEN. 20% of the identified mutations are reported for the first time from Khyber Pakhtunkhwa. In the enrolled cohort, 23 mutations were nonsynonymous SNVs. The frequency of mutations was the highest in PIK3CA, followed by TP53 and PTEN. A total of 13 mutations were found to be highly pathogenic. Four novel mutations were identified on PIK3CA and one each on PTEN and TP53. SAAFEQ-SEQ predicted the destabilizing effect for all mutations. ISPRED-SEQ predicted 9 IS mutations (6 on TP53 and 3 on PIK3CA), whereas no IS mutation was predicted on PTEN. The TP53 IS mutations were TP53R43H, TP53Y73X, TP53K93Q, TP53K93R, TP53D149E, and TP53Q199X; whereas for PIK3CA, the IS mutations were PIK3CAL156V, PIK3CAM610K, and PIK3CAH1047R. Analysis from the ConSurf Web server revealed five SNVs with a highly conserved status (conservation score 9) across TP53 and PTEN. TP53P33R was found predominant in the grade 3 tumors, whereas PTENp.C65S was distributed on ER+, ER-, PR+, PR-, Her2+, and Her2- patients. TP53p.P33R mutation was found to be recurring in the 14/19 (73.6%) patients and, therefore, can be considered as a potential biomarker. Finally, these mutations were studied in the context of their potential association with different hormonal and social factors.
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BACKGROUND: Male breast cancer incidence rises with age with peak in the 6th & 7th decade. It is one of the rare diseases and accounts for less than 1% of all malignancies worldwide. It is usually diagnosed in the late stage with poor prognosis. OBJECTIVE: The purpose of this study was to know the demographic pattern and tumour characteristic of breast cancer in men reported at Institute of Radiotherapy and Nuclear Medicine (IRNUM), Peshawar. METHODS: Retrospective data was collected from the (IRNUM), Peshawar for a period of three years (2006-2008). The evaluation was done from the histopathological reports of mastectomy and biopsy specimens. All male patients in the age group 26-86 year with breast cancer were included in the study. The age of the patients and tumour characteristics recorded were size, grade, type, skin involvement and stage. RESULTS: Total number of male patients with breast cancer were 31 (2.1%) out of the total patients with breast malignancy during the study period with the mean age of 58.3 years. Tumour size ranged from 2 to 12 Cm. with average of 3.6 Cm. Invasive ductal carcinoma was found in 87%, papillary carcinoma in 6.5%, each of malignant fibrous histocytoma and sarcoma in 3.2% cases. Maximum number of patients was of grade II (41%).Patients in whom stage of the disease was known were 22 cases with 45.5% had stage III disease and 32% had stage IV disease. Skin involvement was found positive in 8 (25.8%). CONCLUSION: Due to poor health care system breast cancer is diagnosed in a late stage of the disease and prognosis is poor.
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Neoplasias da Mama Masculina/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama Masculina/patologia , Carcinoma Ductal de Mama/epidemiologia , Carcinoma Papilar/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paquistão/epidemiologiaRESUMO
Hirschsprung's disease (HD), a classic disease of childhood, may rarely escape diagnosis and lead to unique presentations in adults. By definition, the disease involves the rectosigmoid colon and is the result of a birth defect characterised by the absence of nerve cells responsible for the movement of the colon; thereby leading to functional obstruction. We present here a case of an 18-year girl who visited multiple doctors for the complaints of chronic constipation, abdominal distension, and failure to thrive since infancy. Based on a full-thickness rectal biopsy, she was ultimately diagnosed as a case of HD in our Unit. A defunctioning loop ileostomy for colonic decompression, followed by a Swenson Abdominoperineal Pull- Through at a six weeks interval was done, which proved curative.
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Doença de Hirschsprung/diagnóstico , Adolescente , Feminino , Doença de Hirschsprung/complicações , Doença de Hirschsprung/cirurgia , HumanosRESUMO
Less than 100 cases of gestational gigantomastia have been described in literature. The aetiology and risk factors are not well-established. Various treatments have been used with some consensus. We present the case of a 47-year-old female who presented to us with bilateral gigantomastia in her 16th week of gestation. She had massively enlarged breasts which were very painful. Relevant laboratory investigations were normal. An incisional biopsy done prior to, and two trucut samples at presentation to us, showed normal breast tissue proliferation. In the absence of adequate pain control, it was decided to electively terminate the pregnancy and give a trial of tamoxifen. She made a rapid recovery following termination without requiring the use of tamoxifen.
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Aborto Terapêutico/métodos , Mama/anormalidades , Mama/patologia , Hipertrofia/cirurgia , Complicações na Gravidez/cirurgia , Biópsia , Mama/cirurgia , Feminino , Humanos , Hipertrofia/diagnóstico , Pessoa de Meia-Idade , Gravidez , Complicações na Gravidez/diagnósticoRESUMO
A 45-year-old diabetic male who was a farmer by profession, presented to Khyber Teaching Hospital with swelling and redness on the right side of the chest at the level of 8th rib for the past 5 months which was accompanied by fever and pain. He went to a local hospital where he was given broad spectrum antibiotics. He presented again with yellowish discharge from the wound. Dressing of the wound was done and he was referred to Khyber Teaching Hospital. On presentation, there was an open wound of about 4 cm on the right side of the chest wall at the level of 8th rib near the midclavicular line. X-ray revealed a lytic bone lesion near the costo-chondral junction of the 8th rib. CT scan also showed erosive changes at the above mention site. His fasting blood sugar was well above the normal range and his Alkaline Phosphatase was slightly raised. He was started on Insulin. Debridement and dressing were done and samples were taken for investigations. Bone tissue biopsy revealed inflammatory non-caseating tissue. Culture report was positive for Salmonella Typhi which was resistant to Ciprofloxacin. The patient was given antibiotic (co-amoxiclave) treatment to which he responded leading to a satisfactory recovery.
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Osteomielite/microbiologia , Costelas/microbiologia , Infecções por Salmonella/diagnóstico , Diabetes Mellitus , Fazendeiros , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/microbiologia , Salmonella typhiRESUMO
OBJECTIVE: To compare patient-satisfaction, scar-pain and cosmesis between laparoscopic and open-cholecystectomy. STUDY DESIGN: Cross-sectional survey. PLACE AND DURATION OF STUDY: Khyber Teaching Hospital, Peshawar, from August 2012 to May 2014. METHODOLOGY: A total of 400 patients, who had undergone open or laparoscopic cholecystectomy in all units of the Surgical Department, were included. Data was collected on questionnaires given and read to the patients along with counselling and information regarding scar-pain using visual analog score, and satisfaction and cosmesis on a 0 - 10 scale, by a medical professional in the patients' native language. This was done postoperatively on patients' follow-up visits at 1 and 4 weeks. RESULTS: Mean scar pain score at 1 and 4 weeks postoperatively was higher for open-cholecystectomy; 4.96 ±1 and 0.96 ±1, compared to 2.24 ±0.6 and 0, respectively for laparoscopic-cholecystectomy (p < 0.001 and < 0.001). Cosmesis was higher for laparoscopic-group; 8.6 ±1.2 vs. 6.2 ±1.46 for open-cholecystectomy (p < 0.001). Patient-satisfaction was higher for laparoscopic-cholecystectomy; 9.28 ±1.5 vs. 8.32 ±2.3 for open-cholecystectomy (p < 0.001). Mean-cosmesis score was higher for laparoscopic-cholecystectomy for those younger than 40, females and unmarried. Mean patient-satisfaction score was higher for those older than 40 years who had undergone open-cholecystectomy, women who had undergone laparoscopic-cholecystectomy and for unmarried patients who had laparoscopic-cholecystectomy. CONCLUSION: Overall patient-satisfaction and cosmesis scoring was higher for laparoscopic-cholecystectomy especially among females, unmarried and younger than 40 years. Patients of 40 years and older had greater satisfaction scoring for open-cholecystectomy. Therefore, laparoscopic-cholecystectomy should be favoured in females and unmarried patients and those younger than 40 years.
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Imagem Corporal/psicologia , Colecistectomia Laparoscópica/métodos , Colecistectomia/métodos , Cicatriz , Doenças da Vesícula Biliar/cirurgia , Laparoscopia , Satisfação do Paciente , Adulto , Idoso , Colecistectomia Laparoscópica/psicologia , Estudos Transversais , Feminino , Seguimentos , Doenças da Vesícula Biliar/psicologia , Humanos , Pessoa de Meia-Idade , Medição da Dor , Dor Pós-Operatória , Qualidade de Vida , Procedimentos de Cirurgia Plástica , Inquéritos e Questionários , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate the Lintula score in reducing negative appendectomies in the adult population. STUDY DESIGN: Descriptive analytical study. PLACE AND DURATION OF STUDY: Surgical Department, Khyber Teaching Hospital, Peshawar, Pakistan, from August 2012 to April 2014. METHODOLOGY: A total of 408 emergency patients with a clinical diagnosis of acute appendicitis were included in the study. True or negative appendectomy status was determined per-operatively. Lintula score was calculated afterwards and evaluated for various cut-off points. RESULTS: Among the study population, 72 (17.6%) had a normal appendix by operative assessment and 336 (82.4%) had an acutely inflammed appendix. The receiver operating characteristic curve showed that the optimal cut-off point was ≤ 21 with 100% sensitivity, 88.4% specificity and positive and negative predictive values of 97.3% and 100%, respectively. Area under the curve was 0.963 with 90.4% overall accuracy. CONCLUSION: Utilizing the Lintula cut-off point of ≤ 21, negative appendectomies, unnecessary admissions and healthcare cost can all be reduced.
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Apendicectomia , Apendicite/diagnóstico , Técnicas de Apoio para a Decisão , Doença Aguda , Adulto , Idoso , Apendicite/cirurgia , Feminino , Hospitais de Ensino , Humanos , Masculino , Paquistão , Valor Preditivo dos Testes , Curva ROC , Sensibilidade e Especificidade , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Negative appendectomies result in unnecessary admissions, health care burden, and cost. This study was conducted to assess total leukocyte and neutrophil counts as preventive tools in reducing negative appendectomies. METHODS: Data of admitted patients who underwent appendectomies was analyzed. Receiver operator characteristic (ROC) curve analysis of total leukocyte and neutrophil counts was calculated for various cut-off points. Optimum sensitivity, specificity, overall accuracy, and area under the curve was determined. RESULTS: Of the four hundred and eightpatients, true and negative appendicitis by operative assessment was 294 (72.1%) and 114 (27.9%) compared to 311 (76.2%) and 97 (23.8%) by histopathology, respectively. Optimal cut-off for total leukocyte count was >11.9x10(9)/Liter with 87.14% sensitivity and 91.75% specificity. Optimal cut-off point for neutrophil count was >7.735x10(9)/Liter with 98.71% sensitivity and 91.75% specificity. Area under the curve for total leukocyte and neutrophil counts was 0.9603 and 0.9872, respectively with overall accuracy of 91.2% and 97.1%, respectively. CONCLUSION: Normal total leukocyte and neutrophil counts are strongly associated with negative appendectomies. Non-operative measures and careful observation of total leukocyte and neutrophil counts are of paramount importance.