Real world data on long term outcome of neoadjuvant chemotherapy in locally advanced esthesioneuroblastoma and sinonasal tumor with neuroendocrine differentiation - Results from a single centre study.

INTRODUCTION: Esthesioneuroblastoma and sinonasal neuroendocrine carcinoma (SNEC) are the most common histological subtypes of non-squamous Sinonasal Tumors. A multidisciplinary approach is preferred for locally advanced unresectable esthesioneuroblastoma and SNEC. METHODS: From June 2010 to October 2021, 59 patients with esthesioneuroblastoma and SNEC received NACT. NACT consists of 2-3 cycles of Etoposide-Platinum based chemotherapy. Depending upon response and performance status, subsequent therapy was planned. SPSS descriptive statistics were performed for analysis. Kaplan Meir methods were used for the estimation of Progression Free Survival (PFS) and Overall Survival (OS). RESULTS: 45 (76.3 %) Esthesioneuroblastoma and 14 (23.7 %) SNEC patients received NACT. The median age of the population was 45 years (range 20-81 years). The majority of patients received 2-3 cycles of Platinum (Cisplatin or Carboplatin) + Etoposide as NACT. 28 patients (47.5%) underwent surgery and 20 patients (33.9%) received definitive chemoradiotherapy after NACT. The most common grade 3 or above adverse events were anemia (13.6%), neutropenia (27.1), and hyponatremia (45.8%). At the time of analysis, the median PFS was 56 months (95% CI 31 months to 77 months), and the median OS was 70 months (95% CI 56 months to 86 months). The most common late toxicities noticed were metabolic syndrome (42.4%), hyperglycemia (39%), nasal bleeding (33.9%), hypertension (17%), dyslipidemia (8.5%), and hypothyroidism (5.1%). CONCLUSION: The study shows that NACT is safe, and can be easily delivered without any life-threatening toxicities, with a favorable response and improved survival in this subset of patients.

Neoadjuvant chemotherapy in a rare type of very locally advanced sinonasal carcinomas - long-term results from a tertiary care centre.

Introduction: Sinonasal carcinomas are a rare type of head and neck malignancy with various histologies. The outcomes of patients with unresectable locally advanced sinonasal carcinomas are poor. Hence, we performed this analysis to study the long-term outcomes of sinonasal adenocarcinoma (SNAC) and sinonasal undifferentiated carcinomas (SNUC) where neoadjuvant chemotherapy (NACT) has been given followed by local therapy. Methods: 16 patients with SNUC and adenocarcinoma who received NACT were found eligible for the study. Descriptive statistical analysis was performed for baseline characteristics, adverse events and treatment compliance. Kaplan Meir methods were used for the estimation of progression-free survival (PFS) and overall survival (OS). Results: Seven (43.75%) adenocarcinoma and nine (56.25%) SNUC patients were identified. The median age of the whole cohort was 48.5 years. The median number of cycles delivered was 3 (IQR 1-8). The incidence of grade 3-4 toxicity (CTCAE version 5.0) was 18.75%. The response was partial response or better in seven patients (43.75%). Post-NACT 11 patients (n = 15, 73%) were eligible for definitive therapy. The median PFS was 7.63 months (95% CI, 3.23 - NA months) and the median OS was 10.6 months (95% CI, 5.2-51.5 months). Median PFS and OS for those who underwent surgery post-NACT versus those who did not undergo surgery were 36.267 versus 3.7 months (p = 0.012) and 51.5 versus 10.633 months (p = 0.190), respectively. Conclusion: The study shows a favourable role of NACT in improving resectability, significant improvement in PFS and non-significant improvement in OS after surgery.

Prolonged generalized immune response on 18F-FDG PET/CT following COVID-19 vaccination.

The Coronavirus disease 2019 (COVID-19) pandemic continues to be a major public health concern affecting millions of people globally. The COVID-19 vaccination has implications in medical assessment of cancer patients especially undergoing diagnostic imaging such as 18F-fluoro-deoxyglucose (FDG) positron emission tomography with computed tomography (PET/CT). The inflammatory changes following vaccination can cause false positive findings on imaging. We present a case of a patient with esophageal carcinoma who had 18F-FDG PET/CT scan, 8 weeks following booster dose of Moderna COVID-19 vaccination, which showed widespread FDG avid reactive lymph nodes and intense splenic uptake for prolonged duration of approximately 8 months (34 weeks) probably representing generalized immune response. It is important from radiological/nuclear medicine perspective to recognize imaging features of such rare effect of COVID-19 vaccination, which can pose a challenge in assessing 18F-FDG PET/CT scans in cancer patients. It has also opened new avenues for future research evaluating such COVID-19 vaccine-related prolonged systemic immunological response in cancer patients.

Reconstruction of Massive Segmental Distal Femoral Metaphyseal Bone Defects After Open Injury: A Study of 20 Patients Managed with Intercalary Gamma-Irradiated Structural Allografts and Autologous Cancellous Grafts.

BACKGROUND: Our aim was to examine the outcome of gamma-irradiated intercalary structural allografts combined with autologous cancellous grafts in treating large metaphyseal bone defects of the distal femur following open injuries. METHODS: We prospectively included 20 consecutive patients with large metaphyseal bone defects of >4 cm located in the region of the distal femur following open injuries treated between 2010 and 2018, with a mean follow-up of 2 years (range, 2 to 10 years). Of these patients,18 were men and 2 were women. The mean age was 39 years (range, 22 to 72 years). The mean length of the bone defects was 10.1 cm (range, 5.5 to 14.5 cm), and all were in the metaphysis of the distal femur. The surgical technique included initial early debridement and external fixation followed by reconstruction of the bone defect using structural allograft combined with autologous cancellous bone graft harvested from the iliac crest and locking plate fixation. Definitive fixation was performed at an average period of 22.5 days (range, 3 to 84 days) after injury. Osseous union, rate of infection, complications, need for secondary procedures, and functional outcome using the Lower Extremity Functional Scale (LEFS) at the final follow-up were assessed. RESULTS: After excluding 1 patient who was lost to follow-up, 19 patients with complete follow-up were available for analysis. Of those, 13 patients (68%) achieved complete union at both ends of the allograft with host bone without any further intervention. Three patients (16%) developed aseptic nonunion of the proximal end of the allograft requiring 1 additional procedure each to achieve union. Four patients (21%) developed a deep surgical site infection. Of those, 1 elderly patient required above-the-knee amputation following uncontrolled diabetes and infection. A second patient required 2 additional procedures, and a third patient needed 4 additional procedures to achieve union. The fourth patient developed infection after achieving union, and the infection subsided after debridement and implant removal. The mean LEFS score for all 19 patients was 55 (range, 41 to 75). CONCLUSIONS: Use of allograft was a reasonable single-stage alternative solution for massive distal femoral bone defects, which united without additional surgery in two-thirds of the patients and without limb-length discrepancy. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Surgical management of peripheral artery pseudoaneurysm following orthopedic trauma: a report of 14 cases.

PURPOSE: Purpose of this study was to report the etiology, diagnosis, surgical management, and outcome of pseudoaneurysm associated with orthopedic trauma. METHODS: A retrospective review was conducted of all patients presenting to a Level 1 trauma center between 2013 and 2019. Clinical records were reviewed for the mechanism of primary injury, associated fracture pattern, time of presentation, site of involvement, etiology of the pseudoaneurysm, diagnosis, management, and complications. We identified 14 patients with pseudoaneurysm of peripheral arteries following orthopedic trauma. RESULTS: The mean interval between primary injury and the manifestation of clinical symptoms was 88.5 days (range, 16-304 days). There were 3 upper limb injuries and 11 lower limb injuries. The presenting symptoms were pain associated with excessive extremity swelling in most of the patients. A significant drop in hemoglobin (mean fall- 2.9 g/dL) was noted in nine patients. Most common artery involved was the superficial branch of femoral artery and posterior tibial artery followed by the brachial artery. Fractured bone spike was the cause of injury in eight patients and iatrogenic injury in six patients. Diagnosis was confirmed by CT angiography with duplex scan in eight patients, duplex scan alone in one patient, MRI along with duplex scan in one patient. The remaining four patients were diagnosed intraoperatively. Excision of the pseudoaneurysm and ligation of the involved minor arteries was done in eight patients. Surgical repair of the major artery with critical vascular injury was done in six patients. One patient underwent secondary amputation following the anastomotic blowout. CONCLUSION: Early diagnosis of pseudoaneurysm requires knowledge and a high index of suspicion. Surgical reconstruction of major arteries should always be done and ligation of major vessels can lead to catastrophes. Excision of pseudoaneurysm can be done when minor arteries are involved with the presence of good collateral circulation. LEVEL OF STUDY: Level IV Study.

Surgical Management of Parapharyngeal Tumors: Our Experience.

Context Tumors of parapharyngeal space (PPS) are rare and histologically diverse. The management of these tumors requires diligent assessment and planning with due consideration of various anatomical and pathological aspects of the lesion. Aims This retrospective study aims to present our experiences in the clinical and pathological aspects of PPS tumors with a critical evaluation of management. Settings and Design Retrospective analytical study. Methods and Material The electronic medical records of 60 cases of PPS tumors, managed surgically from 2007 to 2017, were reviewed and analyzed using SPSS 22 software. The mean follow-up duration was 44 months. Results The mean age was 45 years with a male-to-female ratio of 1.7 (38:22). The majority of the tumors were benign (71.7%) and the most common presentation being upper neck mass or oropharyngeal mass. Histologically, neurogenic tumors were most common (43.3%) PPS tumors, followed by tumors of salivary gland origin. Magnetic resonance imaging was used as a diagnostic modality in 70% of cases, and computed tomography scan and positron emission tomography/CT were used in 26.7 and 3.3% of cases, respectively. In our study, the diagnostic accuracy of fine-needle aspiration cytology was 71% for benign and 47% for malignant lesions. The most common approach for surgery used was transcervical (72%). Conclusion The study reveals that cranial nerve palsy is the most common complication associated with PPS tumors. Completely resected, malignant tumors originating within PPS have a good prognosis, as compared with tumors extending or metastasized to PPS.

Current updates in management of extremity injuries in polytrauma.

Injury-related morbidity and mortality have been one of the most common causes of loss in productivity across all geographic distributions. It remains to be a global concern despite a continual improvement in regional and national safety policies. The establishment of trauma care systems and advancements in diagnostics and management have improved the overall survival of severely injured. A better understanding of the physiopathological and immunological responses to injury led to a significant shift in trauma care from "Early Total Care" to "Damage Control Orthopedics." While most of these algorithms were tailored to the philosophy of "life before limb," the impact of improper fracture management on disability and societal loss is increasingly being recognized. Recently, "Early Appropriate Care" of extremities has gained importance; however, its implementation is influenced by regional health care policies, available resources, and expertise and varies between low and high-income countries. A review of the literature was performed using PubMed, Embase, Web of Science, and Scopus databases on articles published from 1990 to 2020 using the Mesh terms "Polytrauma," "Multiple Trauma," and "Fractures." This review aims to consolidate on guidelines and available evidence in the management of extremity injuries in a polytraumatized patient to achieve better clinical outcomes of these severely injured.

Management of Tibial Shaft Fractures Distal to TKA Prosthesis by Intramedullary Nail: A Report of Three Cases.

INTRODUCTION: Diaphyseal tibial fractures distal to a well-fixed tibial component although rare present a significant challenge and optimal treatment remains controversial. Displaced periprosthetic tibial shaft fractures are ideally treated with open reduction internal fixation with plate osteosynthesis. However, this treatment method is associated with weight-bearing restrictions, which can be difficult for elderly patients with multiple comorbidities and balance impairment. We present our experience of internal fixation with an intramedullary nail that uses an inferior entry point, standard intramedullary tibial nail, and conventional instrumentation. MATERIALS AND METHODS: Between 2017 and 2018, three patients with acute tibial shaft fractures distal to a TKA (Felix Type 3A) were treated with an intramedullary nail. Preoperative planning involved assessing proximal tibia to ensure adequate room for implant and instrumentation. The average patient age was 66.3 years (range 59-72 years) and all patients were males. All the patients sustained fractures of distal tibial and fibula diaphysis, after a road traffic accident. There were no complications intraoperatively, and all procedures were completed uneventfully. One patient underwent additional fixation of the fibula. RESULTS: All patients achieved a radiological fracture union after an average of 20.6 weeks. There were no fixation failures, or nonunions postoperatively. There were no new symptoms relative to the TKA that could be attributed to the tibial nailing procedure. CONCLUSION: We recommend that this technique can be used primarily for this fracture pattern distal to a TKA, provided there is adequate space to accommodate the nail and instrumentation proximally anterior to the tibial tray.

Masseter Flap for Reconstruction of Defects After Excision of Buccal Mucosa Cancers with Intact Mandible.

Among the reconstructive options available for buccal mucosa defects with an intact mandible, free flap with microvascular anastomosis is the best option. However, in the developing world, with poor resources, limited in- frastructure, and high patient load, this cannot be offered to all patients. We report on the success of the masseter flap for reconstruction of such defects in carefully selected patients. Despite some known limitations, this flap is easy to learn and carries acceptable complications. The results of this flap may not be comparable to those of microvas- cular reconstructions, but they are better than those from other options such as skin graft, nasolabial flap, submental flap, etc. in terms of surgical time required, no donor site morbidity, and minimal aesthetic deformity.

Outcomes of Elective Major Cancer Surgery During COVID 19 at Tata Memorial Centre: Implications for Cancer Care Policy.

BACKGROUND: Overburdened systems and concerns of adverse outcomes have resulted in deferred cancer surgeries with devastating consequences. In this COVID pandemic, the decision to continue elective cancer surgeries, and their subsequent outcomes, are sparsely reported from hotspots. METHODS: A prospective database of the Department of Surgical Oncology was analysed from March 23rd to April 30th, 2020. FINDINGS: Four hundred ninety-four elective surgeries were performed (377 untested and 117 tested for Covid 19 before surgery). Median age was 48 years with 13% (n = 64) above the age of 60 years. Sixty-eight percent patients were American Society of Anaesthesiology (ASA) grade I. As per surgical complexity grading, 71 (14·4%) cases were lower grade (I-III) and 423 (85.6%) were higher grade complex surgeries (IV - VI).Clavien-Dindo ≥ grade III complications were 5.6% (n = 28) and there were no postoperative deaths. Patients >60 years documented 9.3% major complications compared to 5.2% in <60 years (P = 0.169). The median hospital stay was 1 to 9 days across specialties.Postoperatively, 26 patients were tested for COVID 19 and 6 tested positive. They all had higher grade surgeries but none required escalated or intensive care treatment related to COVID infection. INTERPRETATION: A combination of scientific and administrative rationale contributed to favorable outcomes after major elective cancer surgeries. These results support the continuation of elective major cancer surgery in regions with Covid 19 trends similar to India.

Myeloid-derived suppressor cells impede T cell functionality and promote Th17 differentiation in oral squamous cell carcinoma.

Oral tumor microenvironment is characterized by chronic inflammation signified with infiltrating leukocytes and soluble mediators which cause immune suppression. However, how immunosuppressive cells like myeloid-derived suppressor cells (MDSCs) maintain the immunosuppressive tumor microenvironment and influence T cell function in oral squamous cell carcinoma (OSCC) patients remains poorly understood. In the present study, we found that percentages of MDSCs were higher in oral cancer patients compared to healthy individuals and correlated with cancer stage. Monocytic MDSCs (M-MDSCs) were prevalent in the periphery, while granulocytic/polymorphonuclear subset dominated the tumor compartment. M-MDSCs suppressed the lymphocyte proliferation and decreased the CD3-ζ (zeta) chain expression and interferon gamma production. The percentage of M-MDSCs in peripheral blood correlated inversely with CD3-ζ chain expression in T cells of these patients. Interleukin 6 (IL-6)-induced phosphorylated STAT3-regulated programmed cell death ligand 1, CCAAT/enhancer-binding proteins alpha and beta and Interleukin 10 expression in MDSCs. MDSCs inhibited TGF-ß-driven generation of induced regulatory T cells in vitro. M-MDSCs secreted interleukins IL-6, IL-1ß, IL-23 and PGE2 and facilitated T-helper 17 (Th17) cell differentiation which utilizes nitric oxide synthase and cyclooxygenase 2 enzyme activity. Interestingly, OSCC patients showed increased levels of Th17 cells in peripheral blood and tumor tissue. Thus, increased frequency of MDSCs, Th17 cells and decreased expression of CD3-ζ chain portray T cell tolerance and chronic inflammatory state facilitating tumor growth.

Correlation of radiological parameters to functional outcome in complex proximal humerus fracture fixation: A study of 127 cases.

OBJECTIVE: The purpose of this study is to analyze the radiological and functional outcome of complex proximal humerus fractures treated by open reduction and plate fixation, and how radiological parameters correlate with functional outcome. DESIGN: Retrospective study. SETTING: Level-1 trauma center. PATIENTS/METHODS: One hundred twenty-seven patients were analyzed, with a mean follow-up of 5 (3-7) years. OUTCOME MEASUREMENTS: Radiological parameters studied were neck-shaft angle (NSA), greater tuberosity (GT) to articular surface (AS) distance, medial hinge reduction, and presence (or absence) of calcar screw. Functional outcome evaluated by DASH and Constant-Murley (C-M) score. RESULTS: The mean age is 53.8 years. All patients had a union in 14 (12-18) weeks. The mean NSA is 135° (112-155°). One hundred and thirteen patients with an NSA of >120° had a good functional outcome. Fourteen patients with NSA ≤120° had shoulder abduction <90°. The mean GT to AS distance is 7.2 mm (-2 to 16). The superior displacement of GT above AS is associated with abduction of <90° (16 patients). The mean medial gap is 3 mm (0-17). In 14 patients with a medial gap of >4 mm and without calcar screw, varus collapse is observed. All patients had a good outcome on DASH score and 122 patients had good to excellent outcome on C-M score. Five patients with poor outcome on C-M score had NSA <120° and displacement of GT above AS. CONCLUSION: Radiographic indicators for poor outcome are varus angulation with NSA <120°, superior displacement of GT above AS, the presence of medial gap >4 mm, and absence of calcar specific screw. This "terrible triad" of proximal humerus fracture should be avoided during operative fixation.

Anti-Proliferation Effect of Theasaponin E1 on the ALDH-Positive Ovarian Cancer Stem-Like Cells.

Ovarian cancer has the highest mortality rate of all gynecological malignancies and the five-year death rate of patients has remained high in the past five decades. Recently, with the rise of cancer stem cells (CSCs) theory, an increasing amount of research has suggested that CSCs give rise to tumor recurrence and metastasis. Theasaponin E1 (TSE1), which was isolated from green tea (Camellia sinensis) seeds, has been proposed to be an effective compound for tumor treatment. However, studies on whether TSE1 takes effect through CSCs have rarely been reported. In this paper, ALDH-positive (ALDH+) ovarian cancer stem-like cells from two platinum-resistant ovarian cancer cell lines A2780/CP70 and OVCAR-3 were used to study the anti-proliferation effect of TSE1 on CSCs. The ALDH+ cells showed significantly stronger sphere forming vitality and stronger cell migration capability. In addition, the stemness marker proteins CD44, Oct-4, Nanog, as well as Bcl-2 and MMP-9 expression levels of ALDH+ cells were upregulated compared with the original tumor cells, indicating that they have certain stem cell characteristics. At the same time, the results showed that TSE1 could inhibit cell proliferation and suspension sphere formation in ALDH+ cells. Our data suggests that TSE1 as a natural compound has the potential to reduce human ovarian cancer mortality. However, more research is still needed to find out the molecular mechanism of TSE1-mediated inhibition of ALDH+ cells and possible drug applications on the disease.

Does tranexamic acid reduce blood loss during head and neck cancer surgery?

BACKGROUND AND AIMS: Transfusion of blood and blood products poses several hazards. Antifibrinolytic agents are used to reduce perioperative blood loss. We decided to assess the effect of tranexamic acid (TA) on blood loss and the need for transfusion in head and neck cancer surgery. METHODS: After Institutional Review Board approval, 240 patients undergoing supramajor head and neck cancer surgeries were prospectively randomised to either TA (10 mg/kg) group or placebo (P) group. After induction, the drug was infused by the anaesthesiologist, who was blinded to allocation, over 20 min. The dose was repeated every 3 h. Perioperative (up to 24 h) blood loss, need for transfusion and fluid therapy was recorded. Thromboelastography (TEG) was performed at fixed intervals in the first 100 patients. Patients were watched for post-operative complications. RESULTS: Two hundred and nineteen records were evaluable. We found no difference in intraoperative blood loss (TA - 750 [600-1000] ml vs. P - 780 [150-2600] ml, P = 0.22). Post-operative blood loss was significantly more in the placebo group at 24 h (P - 200 [120-250] ml vs. TA - 250 [50-1050] ml, P = 0.009), but this did not result in higher number of patients needing transfusions (TA - 22/108 and P - 27/111 patients, P = 0.51). TEG revealed faster clot formation and minimal fibrinolysis. Two patients died of causes unrelated to study drug. Incidence of wound complications and deep venous thrombosis was similar. CONCLUSION: In head and neck cancer surgery, TA did not reduce intraoperative blood loss or need for transfusions. Perioperative TEG variables were similar. This may be attributed to pre-existing hypercoagulable state and minimal fibrinolysis in cancer patients.

Extracellular 2'5'-oligoadenylate synthetase 2 mediates T-cell receptor CD3-ζ chain down-regulation via caspase-3 activation in oral cancer.

Decreased expression of CD3-ζ chain, an adaptor protein associated with T-cell signalling, is well documented in patients with oral cancer, but the mechanistic justifications are fragmentary. Previous studies in patients with oral cancer have shown that decreased expression of CD3-ζ chain was associated with decreased responsiveness of T cells. Tumours are known to induce localized as well as systemic immune suppression. This study provides evidence that oral tumour-derived factors promote immune suppression by down-regulating CD3-ζ chain expression. 2'5'-Oligoadenylate synthetase 2 (OAS2) was identified by the proteomic approach and our results established a causative link between CD3-ζ chain down-regulation and OAS2 stimulation. The surrogate situation was established by over-expressing OAS2 in a HEK293 cell line and cell-free supernatant was collected. These supernatants when incubated with T cells resulted in down-regulation of CD3-ζ chain, which shows that the secreted OAS2 is capable of regulating CD3-ζ chain expression. Incubation of T cells with cell-free supernatants of oral tumours or recombinant human OAS2 (rh-OAS2) induced caspase-3 activation, which resulted in CD3-ζ chain down-regulation. Caspase-3 inhibition/down-regulation using pharmacological inhibitor or small interfering RNA restored down-regulated CD3-ζ chain expression in T cells induced by cell-free tumour supernatant or rh-OAS2. Collectively these results show that OAS2 leads to impairment in CD3-ζ chain expression, so offering an explanation that might be applicable to the CD3-ζ chain deficiency observed in cancer and diverse disease conditions.

Masseter flap for reconstruction of defects after excision of buccal mucosa cancers with intact mandible.

Among the reconstructive options available for buccal mucosa defects with an intact mandible, free flap with microvascular anastomosis is the best option. However, in the developing world, with poor resources, limited infrastructure, and high patient load, this cannot be offered to all patients. We report on the success of the masseter flap for reconstruction of such defects in carefully selected patients. Despite some known limitations, this flap is easy to learn and carries acceptable complications. The results of this flap may not be comparable to those of microvascular reconstructions, but they are better than those from other options such as skin graft, nasolabial flap, submental flap, etc., in terms of surgical time required, no donor site morbidity, and minimal aesthetic deformity.

An Unusual Course of Segmental Renal Artery Displays a Rare Case of Hilar Nutcracker Phenomenon.

Nutcracker phenomenon or renal vein entrapment is classically seen as a compression of renal vein in between abdominal aorta and superior mesenteric artery with patients being asymptomatic or clinically manifested in the form of nutcracker syndrome as proteinuria, hematuria, flank pain, pelvic congestion in women, and varicocele in men. In this report, we are presenting a case of rare variant of nutcracker phenomenon along with brief review of anatomy, pathophysiology, public health, and clinical significance of nutcracker syndrome. On a routine dissection of an adult male cadaver, we noticed an unusual arrangement of the structures at the hilum of the left kidney showing entrapment of renal vein between left anterior inferior and posterior segmental renal arteries. The variation in the course of left anterior inferior segmental renal artery leads to compression of left renal vein at renal hilum. Therefore, we have named this rare abnormal anatomical entity as hilar nutcracker phenomenon. The structures in the right renal hilum are normal. The objective of this paper is to report an unusual but important variant of nutcracker phenomenon and also give collective knowledge of such anatomical variations in renal vasculature that will help in diagnosing and treating such rare renal disorder.

Glycogen synthase kinase 3 inhibitor protects against microvascular hyperpermeability following hemorrhagic shock.

BACKGROUND: Hemorrhagic shock (HS)-induced microvascular hyperpermeability involves disruption of endothelial cell adherens junctions leading to increase in paracellular permeability. ß-Catenin, an integral component of the adherens junctional complex and Wnt pathway, and caspase 3 via its apoptotic signaling regulate endothelial cell barrier integrity. We have hypothesized that inhibiting phosphorylation of ß-catenin and caspase 3 activity using glycogen synthase kinase 3-specific inhibitor SB216763 would attenuate microvascular hyperpermeability following HS. METHODS: In Sprague-Dawley rats, HS was induced by withdrawing blood to reduce mean arterial pressure to 40 mm Hg for 60 minutes followed by resuscitation. Rats were given SB216763 (600 µg/kg) intravenously 10 minutes before shock. To study microvascular permeability, the rats were intravenously injected with fluorescein isothiocyanate (FITC)-albumin (50 mg/kg), and its flux across the mesenteric postcapillary venules was determined using intravital microscopy. In cell culture studies, rat lung microvascular endothelial cell monolayers grown on Transwell plates were pretreated with SB216763 (5 µM) followed by BAK (5 µg/mL) and caspase 3 (5 µg/mL) protein transfection. FITC-albumin (5 mg/mL) flux across cell monolayers indicates change in monolayer permeability. Activity of canonical Wnt pathway was determined by luciferase assay. Caspase 3 enzyme activity was assayed fluorometrically. RESULTS: The HS group showed significant increase in FITC-albumin extravasation (p < 0.05) compared with sham. SB216763 significantly decrease HS-induced FITC-albumin extravasation (p < 0.05). Pretreatment with SB216763 protected against a BAK-induced increase in rat lung microvascular endothelial cell monolayer permeability and caspase 3 activity but failed to show similar results with a caspase 3-induced increase in monolayer permeability. Wnt3a treatment showed an increase in ß-catenin-dependent T-cell factor-mediated transcription. CONCLUSION: Inhibiting phosphorylation of ß-catenin and caspase 3 activity using glycogen synthase kinase 3-specific inhibitor SB216763 help regulates HS-induced microvascular hyperpermeability.

Ganga hospital open injury score in management of open injuries.

INTRODUCTION: Open injuries of the limbs offer challenges in management as there are still many grey zones in decision making regarding salvage, timing and type of reconstruction. As a result, there is still an unacceptable rate of secondary amputations which lead to tremendous waste of resources and psychological devastation of the patient and his family. Gustilo Anderson's classification was a major milestone in grading the severity of injury but however suffers from the disadvantages of imprecise definition, a poor interobserver correlation, inability to address the issue of salvage and inclusion of a wide spectrum of injuries in Type IIIb category. Numerous scores such as Mangled Extremity Severity Score, the Predictive Salvage Index, the Limb Salvage Index, Hannover Fracture Scale-97 etc have been proposed but all have the disadvantage of retrospective evaluation, inadequate sample sizes and poor sensitivity and specificity to amputation, especially in IIIb injuries. METHODS: The Ganga Hospital Open Injury Score (GHOIS) was proposed in 2004 and is designed to specifically address the outcome in IIIb injuries of the tibia without vascular deficit. It evaluates the severity of injury to the three components of the limb--the skin, the bone and the musculotendinous structures separately on a grade from 0 to 5. Seven comorbid factors which influence the treatment and the outcome are included in the score with two marks each. The application of the total score and the individual tissue scores in management of IIIB injuries is discussed. RESULTS: The total score was shown to predict salvage when the value was 14 or less; amputation when the score was 17 and more. A grey zone of 15 and 16 is provided where the decision making had to be made on a case to case basis. The additional value of GHOIS was its ability to guide the timing and type of reconstruction. A skin score of more than 3 always required a flap and hence it indicated the need for an orthoplastic approach from the index procedure. Bone score of 4 and 5 will require complex reconstruction procedures like bone transport, extensive bone grafting or free fibular graft. Regarding the timing of reconstruction, injuries with a score of 9 or less indicated a low violence trauma and were amenable for early soft tissue reconstruction whereas injuries with a score of 10 or more indicated high violence injuries where a staged reconstruction policy must be followed. CONCLUSIONS: Ganga Hospital Open Injury Score was found to be highly useful in decision making regarding salvage in IIIB injuries. The individual tissue scores were also useful to provide guidance regarding the timing and type of bone and soft tissue reconstruction.

Reconstruction of post-traumatic long segment bone defects of the lower end of the femur by free vascularized fibula combined with allograft (modified Capanna's technique).

PURPOSE: Salvage of long segment bone loss in the limbs particularly near the joints continues to be a challenge to the trauma surgeon. None of the techniques available are universally successful and all share the disadvantages of multi-staged procedures. A reliable single-stage technique would be ideal to reduce the treatment time and the cost of care. We are presenting here our experience of successfully using the modified Capanna technique of combining allograft and free vascularized fibular graft in treating large bone defects in the distal third of the femur. METHODS: Between April 2012 and October 2013, six patients with post-traumatic long segment bone loss in the distal femur had reconstruction of the bone defect by the Capanna technique. The average age was 33 years (range of 18-49 years). The bone defect ranged from 10 to 20 cm (average 15 cm). Five patients had primary reconstruction while one was done after allograft failure. Bone union time and occurrence of any complications were noted. Follow-up ranged from 7 to 24 months (average 15 months). RESULTS: All grafts went onto union. No patient required secondary procedure to achieve union. Average time to union was 6 months. One patient had deep infection and delayed union of distal end of the fibula graft. CONCLUSION: Free vascularized fibular graft combined with allograft increases initial stability, allows early weight bearing, has higher chances of union and is a good single-stage technique of reconstruction of distal third femur defects.