The Added Value of Technetium-99 m Sestamibi Scan in Patients with Primary Hyperparathyroidism and Positive Ultrasound.

BACKGROUND: Neck ultrasound (US) and Technetium-99 m Sestamibi (MIBI) scan are the most commonly used imaging studies for preoperative localization of parathyroid adenomas. The aim of this study was to determine the added value of MIBI scan and its effect on the operative plan via a hypothetical model where a stepwise approach is conducted and MIBI is considered only after the ultrasound is evaluated. METHODS: Patients who underwent parathyroidectomy for primary hyperparathyroidism (PHPT) between 2012 and 2019 at two tertiary centers were included. Data collected included demographic data, preoperative workup, operative findings and follow-up. The added value of MIBI scans was determined for patients with positive ultrasound. RESULTS: A total of 513 patients with positive US result and a MIBI scan were included. If a stepwise approach was conducted then MIBI scan would not change the operative plan in 492 (95.9%). Among the remaining 21 patients, MIBI scan would correctly change the ultrasound-based operative plan in only 12 (2.3%) patients, while incorrectly change the plan in 9 (1.8%), resulting in unnecessary exploration of the contralateral side. In patients with sonographic appearance of a parathyroid gland larger than 1.2 cm, MIBI scan would correctly change the operative plan in only 1 of the 287 (0.35%) patients. CONCLUSIONS: Our study suggests that the routine use of MIBI scans may have limited added value in patients with PHPT and a positive neck ultrasound, especially in those with adenoma size larger than 1.2 cm. Positive ultrasound alone may be sufficient for the preoperative localization of parathyroid disease.

Growth factor receptor-bound protein-7 (Grb7) as a prognostic marker and therapeutic target in breast cancer.

BACKGROUND: Growth factor receptor-bound protein-7 (Grb7) is an adapter-type signaling protein recruited to various tyrosine kinases, including HER2/neu. Grb7-specific inhibitors are in early development. As with other targeted therapies, response to therapy might be associated with target expression. MATERIALS AND METHODS: Tissue microarrays containing 638 primary breast cancer specimens with 15-year patient follow-up were employed to assess Grb7 expression using our Automated QUantitative Analysis method; cytokeratin defines pixels as breast cancer (tumor mask) within the histospot, and Grb7 expression within the mask is measured with Cy5-conjugated antibodies. RESULTS: High Grb7 expression was strongly associated with decreased survival in the entire cohort and in the node-positive subset (P = 0.0034 and P = 0.0019, respectively). On multivariable analysis, it remained an independent prognostic marker (P = 0.01). High Grb7 was strongly associated with high HER2/neu, and coexpression of these molecules was associated with worse prognosis than HER2/neu overexpression alone. CONCLUSIONS: High Grb7 defines a subset of breast cancer patients with decreased survival, indicating that Grb7 might be a valuable prognostic marker and drug target. Coexpression with HER2/neu indicates that cotargeting these molecules might be an effective approach for treating HER2/neu-positive breast cancers. Future studies using Grb7-targeting agents should include assessment of Grb7 levels.

Rapid Cancer Diagnosis and Early Prognosis of Metastatic Risk Based on Mechanical Invasiveness of Sampled Cells.

We provide an innovative, bioengineering, mechanobiology-based approach to rapidly (2-h) establish the in vivo metastatic likelihood of patient tumor-samples, where results are in direct agreement with clinical histopathology and patient outcomes. Cancer-related mortality is mostly due to local recurrence or to metastatic disease, thus early prediction of tumor-cell-fate may critically affect treatment protocols and survival rates. Metastasis and recurrence risks are currently predicted by lymph-node status, tumor size, histopathology and genetic testing, however, these are not infallible and results may require days/weeks. We have previously observed that subpopulations of invasive cancer-cells will rapidly (1-2 h) push into the surface of physiological-stiffness, synthetic polyacrylamide gels, reaching to cell-scale depths, while normal or noninvasive cells do not considerably indent gels. Here, we evaluate the mechanical invasiveness of established breast and pancreatic cell lines and of tumor-cells from fresh, suspected pancreatic cancer tumors. The mechanical invasiveness matches the in vitro metastatic potential in cell lines as determined with Boyden chamber assays. Moreover, the mechanical invasiveness directly agrees with the clinical histopathology in primary-site, pancreatic-tumors. Thus, the rapid, patient-specific, early prediction of metastatic likelihood, on the time-scale of initial resection/biopsy, can directly affect disease management and treatment protocols.

HSP90 as a marker of progression in melanoma.

BACKGROUND: HSP90 chaperones molecules critical for cell survival and malignant progression, including mutated B-raf. HSP90-targeting agents are in clinical trials. No large studies have been conducted on expression of HSP90 in melanomas. MATERIALS AND METHODS: Tissue microarrays containing 414 nevi, 198 primary and 270 metastatic melanomas were assessed using our automated quantitative analysis (AQUA) method of in situ protein measurement; we use S-100 to define pixels as melanocytes (tumor mask) within the array spot, and measure HSP90 expression within the mask using Cy5-conjugated antibodies. RESULTS: HSP90 expression was higher in melanomas than nevi (P < 0.0001) and higher in metastatic than primary specimens (P < 0.0001). No association was seen between high HSP90 expression and survival in the primary or metastatic patient subsets. In primary melanomas, high HSP90 expression was associated with higher Clark level (P = 0.0167) and increased Breslow depth (P < 0.0001). CONCLUSIONS: HSP90 expression was significantly higher in tumors than nevi and was associated with disease progression, indicating that it might be a valuable drug target in melanoma, as well as a useful diagnostic marker. Prospective studies are needed to confirm the diagnostic role of HSP90, as well as the predictive role of HSP90 expression in patients treated with HSP90 inhibitors.

Microsurgical management of penetrating peripheral nerve injuries: pre, intra- and postoperative analysis and results.

BACKGROUND AND METHODS: Clinical and electrophysiological motor function data were compared before and after microsurgical repair of penetrating peripheral nerve injuries. Sixty-four patients totaling 74 injured nerves (25 gunshot wounds, 49 stab wounds) were treated with external and interfascicular neurolysis and/or interfascicular nerve grafts. Microsurgery was performed 2-12 months after the injury (Group 1, 33 patients,) and 12 months-60 years after the injury (Group 2, 31 patients). The postoperative clinical and electrophysiological follow-up period ranged between 1 and 5 years. RESULTS: A statistically significant improvement in muscle strength occurred after the microsurgery, compared to before repair, gunshot wounds (p < 0.001), stab wounds (p < 0.001). Intraoperative and postoperative electrophysiological analysis showed statistically significant improvement. TIMING OF SURGERY: No statistically significant difference in muscle strength occurred between the 2 groups after the surgery, each showing statistically significant improvement, Group 1 (p < 0.001), Group 2 (p < 0.001). Patients above and below age of 40 showed an improvement in muscle strength after microsurgery, (p < 0.001) and (p < 0.001), respectively. CONCLUSION: Microsurgery can progressively improve nerve function in penetrating peripheral nerve injuries and lead to significant functional improvement, even when it is delayed for more than one year after the injury.

Proceedings of resources for optimal care of acute care and emergency surgery consensus summit Donegal Ireland.

BACKGROUND: Opportunities to improve emergency surgery outcomes exist through guided better practice and reduced variability. Few attempts have been made to define optimal care in emergency surgery, and few clinically derived key performance indicators (KPIs) have been published. A summit was therefore convened to look at resources for optimal care of emergency surgery. The aim of the Donegal Summit was to set a platform in place to develop guidelines and KPIs in emergency surgery. METHODS: The project had multidisciplinary global involvement in producing consensus statements regarding emergency surgery care in key areas, and to assess feasibility of producing KPIs that could be used to monitor process and outcome of care in the future. RESULTS: Forty-four key opinion leaders in emergency surgery, across 7 disciplines from 17 countries, composed evidence-based position papers on 14 key areas of emergency surgery and 112 KPIs in 20 acute conditions or emergency systems. CONCLUSIONS: The summit was successful in achieving position papers and KPIs in emergency surgery. While position papers were limited by non-graded evidence and non-validated KPIs, the process set a foundation for the future advancement of emergency surgery.

Erratum to: The management of intra-abdominal infections from a global perspective: 2017 WSES guidelines for management of intra-abdominal infections.

[This corrects the article DOI: 10.1186/s13017-017-0141-6.].

SPINE: an integrated tracking database and data mining approach for identifying feasible targets in high-throughput structural proteomics.

High-throughput structural proteomics is expected to generate considerable amounts of data on the progress of structure determination for many proteins. For each protein this includes information about cloning, expression, purification, biophysical characterization and structure determination via NMR spectroscopy or X-ray crystallography. It will be essential to develop specifications and ontologies for standardizing this information to make it amenable to retrospective analysis. To this end we created the SPINE database and analysis system for the Northeast Structural Genomics Consortium. SPINE, which is available at bioinfo.mbb.yale.edu/nesg or nesg.org, is specifically designed to enable distributed scientific collaboration via the Internet. It was designed not just as an information repository but as an active vehicle to standardize proteomics data in a form that would enable systematic data mining. The system features an intuitive user interface for interactive retrieval and modification of expression construct data, query forms designed to track global project progress and external links to many other resources. Currently the database contains experimental data on 985 constructs, of which 740 are drawn from Methanobacterium thermoautotrophicum, 123 from Saccharomyces cerevisiae, 93 from Caenorhabditis elegans and the remainder from other organisms. We developed a comprehensive set of data mining features for each protein, including several related to experimental progress (e.g. expression level, solubility and crystallization) and 42 based on the underlying protein sequence (e.g. amino acid composition, secondary structure and occurrence of low complexity regions). We demonstrate in detail the application of a particular machine learning approach, decision trees, to the tasks of predicting a protein's solubility and propensity to crystallize based on sequence features. We are able to extract a number of key rules from our trees, in particular that soluble proteins tend to have significantly more acidic residues and fewer hydrophobic stretches than insoluble ones. One of the characteristics of proteomics data sets, currently and in the foreseeable future, is their intermediate size ( approximately 500-5000 data points). This creates a number of issues in relation to error estimation. Initially we estimate the overall error in our trees based on standard cross-validation. However, this leaves out a significant fraction of the data in model construction and does not give error estimates on individual rules. Therefore, we present alternative methods to estimate the error in particular rules.

2016 WSES guidelines on acute calculous cholecystitis.

Acute calculus cholecystitis is a very common disease with several area of uncertainty. The World Society of Emergency Surgery developed extensive guidelines in order to cover grey areas. The diagnostic criteria, the antimicrobial therapy, the evaluation of associated common bile duct stones, the identification of "high risk" patients, the surgical timing, the type of surgery, and the alternatives to surgery are discussed. Moreover the algorithm is proposed: as soon as diagnosis is made and after the evaluation of choledocholitiasis risk, laparoscopic cholecystectomy should be offered to all patients exception of those with high risk of morbidity or mortality. These Guidelines must be considered as an adjunctive tool for decision but they are not substitute of the clinical judgement for the individual patient.

Erratum to: 2016 WSES guidelines on acute calculous cholecystitis.

[This corrects the article DOI: 10.1186/s13017-016-0082-5.].

Lung preconditioning with N-acetyl-L-cysteine prevents reperfusion injury after liver no flow-reflow: a dose-response study.

BACKGROUND: Circulating xanthine oxidase activity and the generated oxidants have been linked to lung reperfusion injury from no flow-reflow conditions in other organs after organ transplantation or surgery. N-acetyl-1-cysteine (NAC), an oxidant scavenger, promotes glutathione in its reduced form (GSH) that is depleted during ischemia. We have recently demonstrated its efficacy in protecting lungs from reperfusion injury if administered during reperfusion of postischemic liver. We now investigated whether preconditioning of lungs with NAC could attenuate lung respiratory or vascular derangement after no flow-reflow (ischemia-reperfusion, IR) and if this depends on lung GSH levels. METHODS: Rat isolated livers were stabilized and perfused with modified Krebs-Henseleit solution (KH) (control, n=12) or made ischemic (no flow, IR-0, n=12) for 2 hr. Meanwhile, lungs were isolated, ventilated, and stabilized (KH+bovine albumin 5%). Serial perfusion (15 min) of liver+lung pairs took place followed by lung only recirculation (45 min) with the accumulated solution. Another three controls and three ischemic groups included lungs treated during stabilization with NAC at 100 mg x kg(-1), 150 or 225 mg x kg(-1) (in 2.5, 3.7 or 5.5 mmol solutions, respectively). Results. Ischemic liver damage, expressed by circulating hepatocellular constituents, was associated with pulmonary artery and ventilatory pressure increases by 70-100% of baseline, abnormal wet-to-dry weight ratio, and abnormal bronchoalveolar lavage volume and content in the IR-0 (nontreated) and the IR-100 and IR-225 pretreated lungs. NAC-150 pretreatment afforded preservation for most parameters. GSH content in the IR-150 lung tissue was only 11% higher than that of IR-225, but 2-fold that in IR-0 and IR-100 GSH lungs. CONCLUSION: Lung preconditioning with NAC prevents reperfusion injury but not in a dose-related manner. Although enhanced GSH tissue content explains lung protection, GSH-independent NAC activity is another possibility.

Methylene blue abolishes aortal tone impairment induced by liver ischemia-reperfusion in a dose response manner: an isolated-perfused double-organ rat model study.

Liver ischemia-reperfusion (IR) generates remote organ reperfusion injury attributable to oxidative mediators. We tested the protective properties of methylene blue (MB) on aortal dysfunction. An ex vivo rat liver-aortal ring model was used to study the results of aortal exposure to post-ischemia (IR) hepatic effluent and its response to phenylephrine and isosorbide dinitrate in the absence or presence of increasing concentrations of MB in the effluent. Aortal incubation with IR effluents resulted in abnormal contraction. Ring's response to the vasoactive drugs was abnormally weak both during and following this exposure. Return to stabilization tone was irregular. MB (1.28 mM) best avoided overall dysfunction; 0.86 mM was partially effective, and 0.42 mM was ineffective. Nitrite/nitrate levels were similar to controls in the only IR 1.28 mM perfusate. Liver IR interferes with aortal tone and its response to vasoactive drugs, probably via oxidative interaction with nitric oxide. MB reverses these effects in a dose-dependent fashion.

Impairment of aortal tone by no flow-reflow conditions and its partial amelioration by mannitol.

BACKGROUND: Although postischemic cardiac or pulmonary dysfunction can relate to the impact of remotely generated oxygen stress mediators on the heart, their direct effect on the vascular bed remains unresolved. Thus, we tested these remote effects in an ex-vivo double organ model. METHODS: After stabilization With Krebs-Henseleit solution, isolated rat livers were either perfused or made ischemic for 2 hours. Aortic rings were stabilized, immersed in postischemic liver perfusates and their functions were tested. Some organs originated from donors fed with tungstate, whereas others had mannitol (0.25 g/kg) in the buffer. RESULTS: Incubation of aortic rings with postischemic hepatic effluent resulted in protracted contraction. Spasm was slightly lesser when the livers were pretreated with tungstate or exposed to mannitol, but worse in pretreated rings. The return to basal tone was abrupt in all ischemia-reperfusion aortae. The response of the rings to phenylephrine under the influence of the ischemia-reperfusion hepatic effluent was deficient. Mannitol prevented most abnormal responses. CONCLUSIONS: Aortal tone impairment can occur by direct influence of the ischemia-reperfusion liver. It cannot be attributed entirely to xanthine oxidase, but also to other hepatic-released factors.

Anaesthesia and critical care considerations in nerve agent warfare trauma casualties.

Nerve agents (NA) (tabun, sarin, suman, VX) have been stocked around the world for some time and still present a major threat to civilian as well as to military populations. Since NA can be delivered through both an aerial spray system and a ballistic system, victims could suffer both NA intoxication and multiple trauma necessitating urgent surgical intervention followed by intensive care. These patients can be expected to be extremely precarious neurologically, respiratorily and haemodynamically. Moreover, their clinical signs can be misleading. Further exacerbating the problem is the fact that interactions of NA with the pharmacological agents used for resuscitation and/or during anaesthesia can aggravate organ instability even more and possibly cause systemic collapse. There are no protocols for perioperative critical care and early assessment or for the administration of anaesthesia for surgical interventions in such combined multiple trauma and intoxicated casualties. We propose a scheme for the administration of critical care and anaesthesia based on the scant anecdotal reports that have emerged after the occurrence of local accidents involving NA intoxication and on the neuropharmacological knowledge of the pesticide organophosphate poisoning database, these compounds being related chemical substances.

Reduction of surgery-induced peritoneal adhesions by methylene blue.

BACKGROUND: The possible involvement of inflammatory mediators such as nitric oxide (NO), and reports of protective effects of antioxidants, led us to test the effectiveness of methylene blue and NO synthesis inhibitor in reducing adhesion formation. METHODS: Generation of adhesions in rats, by scraping the anterior uterine horn wall, was followed by intraperitoneal administration of saline methylene blue, or N alpha-t-BOC-omega-nitro-L-arginine. Additional rats received identical treatments, but without the serosal damage. Two weeks later, formation of adhesions was quantitatively graded. RESULTS: Adhesions were found in <5% of the rats with the sham surgery, regardless of treatment. In the experimental group, >95% of the rats treated with saline or NO synthetase inhibitor had severe adhesions, in contrast to 5% of the methylene blue treated rats. Severity of adhesion was lower in the methylene blue group (P <0.001). CONCLUSIONS: Methylene blue was very effective in preventing formation of peritoneal adhesions. Its activity is probably through inhibition of free-radical generation and not of nitric oxide action.

Terror bombing-mechanisms, consequences and implications.

Our objective in this review is to describe the unique features of bombing injury and to outline some special elements of their management. This is to allow the timely improvement and adjustment of existing mass casualty protocols. Forensic studies, detonation and explosion, mechanisms of injury in explosion and their bodily effects, chemical effects of the explosive, site of the explosion and the wounding potential, the Multidimensional Injury Pattern, diagnostic evaluation of Multidimensional Injury Pattern, and surgical and treatment dilemmas associated with it are described and discussed.

Hypothermic blood substitution enables resuscitation after hemorrhagic shock and 2 hours of cardiac arrest.

Uncontrollable hemorrhage accounts for a large proportion of total mortality in both civilian (31%) and military (47%) trauma victims. Hypothermia is a relatively safe method that could provide total body protection during hypovolemic shock and facilitate surgical intervention as a potentially life-saving procedure. This study tested the hypothesis that profound hypothermia and complete blood replacement in an established canine model, would facilitate resuscitative therapy from exsanguinating hypovolemic shock. Adult dogs were prepared for extracorporeal bypass using closed-chest peripheral cannulation under general anesthesia. Controlled hypotensive, hemorrhagic shock (mean arterial blood pressure < 50 mmHg) was induced for 30 min at normal temperature followed by temporary resuscitation using crystalloid infusion for approximately 10 min. Using our established procedure, the dogs were then cooled externally to 27 degrees C before initiating blood substitution with Hypothermosol (Cryomedical Sciences, Inc. Rockville, MD) via the extracorporeal pump. The heart was arrested during further cooling to below 10 degrees C and Hypothermosol was recirculated for 2 hr, with (3 dogs) or without (5 dogs) 1 hr of circulatory arrest. During rewarming the animals were autotransfused, weaned from the pump, and allowed to recover. All dogs (n = 8) survived, all but one with complete neurologic recovery: blood chemistry samples examined immediately after the procedure showed significant differences (p < 0.05) in only a few parameters, including creatine kinase (CK-BB and CK-MB), compared with the previous group of control dogs. The consistent survival of dogs showing apparently normal neurologic, physiologic, and biochemical recovery supports the concept that profound hypothermia using a protective hypothermic blood substitute could provide time for therapeutic resuscitation of currently intractable trauma cases.

The impact of advanced trauma life support course on graduates with a non-surgical medical background.

The aim of this study was to assess advanced trauma life support (ATLS) and combat trauma life support (CTLS) skills implementation among general practising physicians, its perceived utility in their routine daily practice as well as in their potential army combat assignments. One hundred and ten physicians, graduates of ATLS and CTLS courses, from the subspecialties of geriatrics, psychiatry and family medicine, were surveyed by telephone, to answer a specially designed questionnaire. The response rate was 82%. Professional distribution was: 6.6% geriatrics; 46.7% family physicians; and 46.7% psychaitrists. The number of trauma events treated by these physicians in their post-course practise was: geriatrics-three; family physicians-30; psychiatrists-18. We believe that a properly designed ATLS course, executed and applied to general practitioners, can be highly beneficial to trauma victims.

The management of stab wounds to the heart with laceration of the left anterior descending coronary artery.

Penetrating cardiac injuries are an increasing cause of traumatic deaths in urban areas. The management of these injuries has undergone a transition from simple pericardiocentesis to cardiac ultrasound evaluation in the stable patient, and emergency thoracotomy and repair of myocardial wounds in the unstable patient in extremes. The incidence of traumatic coronary artery injury is not accurately known because not all victims are examined. With the improvement in emergency medical services, including speed of transportation of these patients, better resuscitation, and knowledgeable use of cardiac ultrasound or emergency room thoracotomy, more patients with coronary artery injuries will survive and reach the operating room. The operative management of the injured coronary artery is dependant on the location of the injury and whether there is myocardial dysfunction. Distal injuries with small myocardial infarction should be treated by ligation alone. Proximal injury and those injuries associate with larger area of ischaemia or infarction are best treated with coronary artery bypass. The role of cardiopulmonary bypass pump in these patients should be evaluated depending on the homodynamic stability of the patient. We present two cases of cardiac stab wounds with transection of the left anterior descending (LAD), which were successfully managed. A literature review regarding the management of combined cardiac and coronary artery injuries is also provided.

Return visits to the emergency room after minor trauma from motor vehicle accidents.

Most patients with minor trauma following motor vehicle accidents (MVAs) are discharged from the emergency room (ER) of a trauma centre after evaluation and observation. Some return with similar or additional symptoms. This study aimed to determine which patients returned, if any injuries had been missed, and what should be the policy of medical management. We reviewed the records of 8836 patients with minor trauma following MVAs who were examined in an inner city trauma centre during 1997. When the group of patients who returned to the emergency room (n = 160) was compared with the whole post-MVA minor trauma group, the former was found to have more males (75.6% vs. 55.9%), younger age (36.31 years vs. 39.72 years), more motorcyclists than drivers, passengers and pedestrians ( p < 0.002, for the three variables), and had more multi-site injures. During the return visits the patients stayed longer in the emergency room, were examined by more consultants and had repeated radiological evaluations and tests, compared with the initial visit. However, in none of the patients was the initial diagnosis revised nor were additional injuries found and consequently the initial management was not changed in any of them. It is concluded that the initial thorough evaluation by the primary traumatologist is adequate for MVA patients with minor trauma. These patients do not require any follow up in specialized clinics, and are best managed in the community by their general practitioners.