Caspase-1 inhibition by VX-765 administered at reperfusion in P2Y12 receptor antagonist-treated rats provides long-term reduction in myocardial infarct size and preservation of ventricular function.

Patients with acute myocardial infarction receive a P2Y12 receptor antagonist prior to reperfusion, a treatment that has reduced, but not eliminated, mortality, or heart failure. We tested whether the caspase-1 inhibitor VX-765 given at reperfusion (a requirement for clinical use) can provide sustained reduction of infarction and long-term preservation of ventricular function in a pre-clinical model of ischemia/reperfusion that had been treated with a P2Y12 receptor antagonist. To address, the hypothesis open-chest rats were subjected to 60-min left coronary artery branch occlusion/120-min reperfusion. Vehicle or inhibitors were administered intravenously immediately before reperfusion. With vehicle only, 60.3 ± 3.8% of the risk zone suffered infarction. Ticagrelor, a P2Y12 antagonist, and VX-765 decreased infarct size to 42.8 ± 3.3 and 29.2 ± 4.9%, respectively. Combining ticagrelor with VX-765 further decreased infarction to 17.5 ± 2.3%. Similar to recent clinical trials, combining ticagrelor and ischemic postconditioning did not result in additional cardioprotection. VX-765 plus another P2Y12 antagonist, cangrelor, also decreased infarction and preserved ventricular function when reperfusion was increased to 3 days. In addition, VX-765 reduced infarction in blood-free, isolated rat hearts indicating at least a portion of injurious caspase-1 activation originates in cardiac tissue. While the pro-drug VX-765 only protected isolated hearts when started prior to ischemia, its active derivative VRT-043198 provided the same amount of protection when started at reperfusion, indicating that even in blood-free hearts, caspase-1 appears to exert its injury only at reperfusion. Moreover, VX-765 decreased circulating IL-1ß, prevented loss of cardiac glycolytic enzymes, preserved mitochondrial complex I activity, and decreased release of lactate dehydrogenase, a marker of pyroptosis. Our results are the first demonstration of a clinical-grade drug given at reperfusion providing additional, sustained infarct size reduction when added to a P2Y12 receptor antagonist.

THORACODORSAL ARTERY PERFORATOR FLAP FOR UPPER LIMB RECONSTRUCTION.

BACKGROUND: Thoracodorsal artery perforator flap (TAP) is a feasible option to reconstruct defects in upper limb where only skin and subcutaneous tissue is required. METHODS: This case series was carried out at department of Plastic and Reconstructive Surgery Combined Military Hospital Rawalpindi. A total of 5 patients with upper limb defects were reconstructed with thoracodorsal artery musculocutaneous perforator flaps. Among them, 3 were pedicled and two free TAP flaps. All flaps except one pedicled flap were raised on a single perforator pedicle. Recipient sites were one axilla, two shoulder regions and two hands. The soft tissue defects in the patients had resulted from burns, trauma, wide local excision of synovial sarcoma and surgery for hidradenitis suppurativa. Preoperative hand held Doppler ultrasound was used to locate and mark the perforator. RESULTS: All flaps survived without significant complications. All flaps were hyperemic in the immediate postoperative period. We designed and raised all the five flaps on eccentrically placed perforators. All the raised perforators originated from the descending branch of the thoracodorsal artery. The donor sites were closed primarily with linear scars in all cases except one, in which partial closure was accomplished with split thickness skin grafting (STSG). CONCLUSION: The thoracodorsal artery perforator flap has great potential for reconstructing large, relatively shallow, defects of upper limb because of its suitable skin quality, texture and appropriate thickness, as well as hidden donor site, a reliable pedicle and sparing of muscle unit.

Sphenoid Wing Dysplasia: Report Of 3 Cases.

Sphenoidal Dysplasia is the absence of complete or a part of sphenoid bone, most commonly the greater wing of sphenoid. It can occur as an isolated deformity or in Neurofibromatosis-1 (NF1). Features of NF1 include café au lait spots, inguinal or axillary freckling, neurofibromas, optic gliomas, scoliosis and tibial deformity. Our study is retrospective case series of 3 cases of Sphenoid wing dysplasia. There was 1 case of isolated bone defect, 1 case of NF-1 and 1 case of operated Craniofacial Fibrous Dysplasia involving the sphenoid wing. There were 2 primary operated cases while 1 was operated secondarily. There was resolution of pulsatile exophthalmos in patient with sphenoid and temporal bone defect. Patient with facial deformity NF1 was debulked to the satisfaction of the patient, the patient however declined surgery to correct the sphenoid bone deformity. The 3rd patient was a re-do surgery patient in which the previous implant material was removed and the CSF rhinorrhoea, the patient did not consent to the correction of vertical orbital dystopia. Sphenoid wing dysplasia is a complex deformity requiring multi speciality care and treatment planning. With meticulous planning and surgery, good results can be achieved as shown in our case series.

Quality of life assessment in patients with locally advanced head and neck malignancy after ablative surgery and reconstruction with microvascular free flaps.

OBJECTIVE: To assess the improvement in Quality Of Life (QOL) after ablative surgery in locally advanced head and neck malignancies by microvascular free flaps reconstruction. STUDY DESIGN: Quasi-experimental. PLACE AND DURATION OF STUDY: Department of Plastic Surgery, Combined Military Hospital, Rawalpindi, from September 2005 to February 2007. METHODOLOGY: A total of 44 patients with locally advanced stage III and IV malignancy of head and neck were included in the study. All patients were treated with ablative surgery and reconstruction with microvascular free flaps. QOL was assessed by using a scoring questionnaire (including 5 parameters for extra oral cancers including physical and role function, body image, weight loss score and pain donor site morbidity; and an additional 5 parameters for intraoral tumours that included swallowing, speech, drooling of saliva and mouth opening). A high score indicated a poor QOL. Patients were assessed pre-operatively and then at 2, 4 and 6 months postoperatively. RESULTS: Mean accumulative score and mean individual parameter scores for both extra- and intraoral tumours were significantly improved (p < 0.05). CONCLUSION: Microvascular free flap reconstruction after ablative surgery in locally advanced head and neck malignancy had a profound impact on the improvement of QOL. There was an initial deterioration of physical scores postoperatively and postradiotherapy, followed by gradual improvement. By the end of 6 months, it surpassed the pre-operative QOL scores.

Surgical correction of grade III hypertelorism.

Orbital hypertelorism is an increased distance between the bony orbits and can be caused by frontonasal malformations, craniofacial clefts, frontoethmoidal encephaloceles, glial tumors or dermoid cysts of the root of the nose, and various syndromic or chromosomal disorders. We report a series of 7 cases of hypertelorism that were treated in our hospital. The underlying causes in our series were craniofacial clefts 0 to 14 (4 cases), craniofacial clefts 1 to 12 (1 case), and frontonasal encephalocele (2 cases), all congenital. Surgical techniques used to correct the deformity were box osteotomy and medial wall osteotomy with or without calvarial and rib grafts. A few of our cases were reoperations with specific challenges.

Increasing mortality from ischaemic heart disease in China from 2004 to 2010: disproportionate rise in rural areas and elderly subjects. 438 million person-years follow-up.

Aims: We sought to ascertain the changes in mortality from ischaemic heart disease (IHD) from 2004 to 2010 in China as the sheer size of China's population makes disease patterns relevant globally. Methods and results: Data on IHD mortality were obtained from the Chinese Centre for Disease Control and Prevention National Disease Surveillance Point System, which includes 161 counties and a population of over 73 million-a representative sample of over 6% of the entire population of China. Both crude and World Health Organization (WHO)-standardized IHD mortality increased, in both men and women and in both urban and rural locations, during the study period, demonstrating the effect of urbanization, economic growth, and epidemiological transition on cardiovascular health. WHO-standardized IHD mortality increased for rural males by 9.2% per year (95% CI: 6.7-11.7%; P < 0.0001), and the trend was statistically significantly higher (P = 0.0001) than in urban males by 6.4% per year (95% CI: 3-10%; P = 0.02). WHO-standardized IHD mortality rate increased for rural females by 7.0% per year (95% CI: 4.6-9.4%; P < 0.0001); this was statistically significantly higher than urban females by 4.3% per year (95% CI: 1-8%; P = 0.02). The age group over 80 years showed the greatest increase in IHD mortality. Conclusions: Mortality from IHD is increasing in China, in contrast to decreasing in other countries. This is largely driven by increasing IHD mortality in rural areas and subjects over 80 years old. This needs urgent attention by public health workers and policymakers.

Tuberculous tenosynovitis: a cause of Carpal Tunnel Syndrome.

OBJECTIVE: To highlight the presentation of tuberculous tenosynovitis as Carpal Tunnel Syndrome (CTS). METHODS: A descriptive study conducted with purposive sampling on the patients presenting between April 2004 to January 2005 to the department of Plastic Surgery, CMH Rawalpindi, with the clinical picture of CTS. Symptoms and signs were recorded. The carpal tunnels were explored under nerve blocks. Where tenosynovitis was observed per-operatively, specimen of excised synovium were sent for histo-pathological examination, acid fast stains and bacterial cultures, to ascertain or rule out the presence of tuberculosis. RESULTS: A total of 53 patients predominantly males were included in the study. The median age was 43 years and average duration of symptoms was 9 months. Tenosynovitis was observed in three patients (6%) per-operatively, with histopathology suggestive of Tuberculous tenosynovitis. Point Prevalence of tuberculous tenosynovitis as a cause of CTS was 6%. These patients reported clinical improvement with anti-tuberculosis treatment. NCS/EMG co-related well with clinical relief. CONCLUSION: Tuberculous tenosynovitis is an uncommon cause of median nerve compression at the wrist. As symptoms are usually typical of CTS, diagnosis is frequently missed. Consideration of the possibility, examination of the opened canal at surgery and proper treatment can result in a successful outcome.

Rotation-transposition correction of nasal deformity in Tessier number 1 and 2 clefts.

OBJECTIVE: To formulate a standardized procedure for repair of the nasal component of Tessier number 1 and 2 clefts. PATIENTS AND METHODS: The procedure was performed from 1998 to 2007 in 13 patients with congenital nasal clefts of different degrees of expression corresponding to Tessier 1 and 2. The patients' ages ranged from 3 months to 28 years. There were 10 male and three female patients. In the absence of any standard published technique for these rare defects, we devised our own method, which we find uniformly applicable to all such cases. We use a composite muco-chondro-cutaneous lateral alar flap to recreate the alar rim. The resulting defect on the lateral nasal wall is then covered with a transposition flap from the dorsum. An alar rim z-plasty was added in cases where notching was evident. RESULTS: In all cases, no problem of flap viability was encountered and all healed well with minimal scarring. The postoperative results were satisfactory and have remained stable over an average 6-month follow-up period. CONCLUSIONS: We recommend this technique to be used for the correction of nasal deformity associated with Tessier clefts number 1 and 2. We feel that this technique is relatively simple and easily reproducible.