Pediatric Medullary Thyroid Carcinoma: Clinical Presentations and Long-term Outcomes in 144 Patients Over Six Decades.

CONTEXT: Sporadic medullary thyroid carcinoma (sMTC) rarely occurs in childhood and no studies have specifically focused on this entity. OBJECTIVE: To describe the clinical presentations and long-term outcomes of a large cohort of children and young adults with sMTC compared with hereditary MTC (hMTC). METHODS: Retrospective study of 144 patients diagnosed with MTC between 1961-2019 at an age ≤21 years and evaluated at a tertiary referral center. RESULTS: In contrast to hMTC (n=124/144, 86%), patients with sMTC (n=20/144, 14%) are older (p<0.0001), have larger tumors (p<0.0001), a higher initial stage grouping (p=0.001) and have more structural disease (p=0.0045) and distant metastases (DM) (p=0.00084) at last follow up, but are not more likely to die from MTC (p=0.42). Among 77 patients diagnosed clinically, not by family history (20/20 sMTC and 57/124 hMTC), there was no difference in the initial stage (p=0.27), presence of DM at diagnosis (p=1.0), disease status at last follow-up (p=0.13), overall survival (p=0.57), or disease specific survival (p=0.87). Of the twelve sMTC tumors that underwent somatic testing, eleven (91%) had an identifiable alteration: ten RET gene alterations and one ALK fusion. CONCLUSIONS: sMTC is primarily a RET-driven disease that represents 14% of childhood-onset MTC in this cohort. Pediatric sMTC patients are older, present with clinical disease at a more advanced TNM classification, and have more persistent disease at last follow up compared with hMTC, but these differences disappear when comparing those presenting clinically. Somatic molecular testing should be considered in sMTC patients who would benefit from systemic therapy.

Continuous Veno-Venous Hemofiltration During Intercontinental Aeromedical Evacuation.

Overseas contingency operations which occur in areas lacking medical infrastructure pose challenges to the stabilization and transportation of critically ill patients. In particular, metabolic derangements resulting from acute kidney injury (AKI) make long-distance aeromedical evacuation risky. Here, we report the first modern use of in-flight continuous veno-venous hemofiltration (CVVH) for intercontinental aeromedical evacuation. Hospital and transport records were reviewed for a 31-yr-old male active duty service member who sustained 40% total body surface area full thickness burns after high-voltage electrical exposure in the southern Philippines. He was evacuated to the Burns Centre at Singapore General Hospital, where CVVH was initiated for anuric AKI secondary to rhabdomyolysis. The United States Army Institute of Surgical Research (USAISR) Burn Flight Team transported the patient to the USAISR Burn Center at Fort Sam Houston, TX, USA. CVVH was performed in-flight for 15 h out of 19.5 h of total flight time. CVVH settings were maintained as follows: blood flow 250 mL/min; replacement fluid rate 3,500 mL/h; and no ultra-filtrate removal. Unfractionated heparin at 500 units/h was utilized for regional anticoagulation. No filter clotting was encountered; a planned filter change was performed during a midway refueling stop. Pre-flight hyperkalemia was managed with low-potassium replacement fluid. No fluid was removed in the setting of large wound insensible losses. The patient remained hemodynamically stable and required no vasoactive medications. Continuous veno-venous hemofiltration can be used safely during high-altitude flight to evacuate casualties with AKI from distant contingency operations. The use of portable hemodialysis equipment in this case also proves the feasibility of deploying renal replacement therapies to more forward facilities than previously considered.

Digital image correlation techniques for strain measurement in a variety of biomechanical test models.

PURPOSE: Previous biomechanical studies have estimated the strains of bone and bone substitutes using strain gages. However, applying strain gages to biological samples can be difficult, and data collection is limited to a small area under the strain gage. The purpose of this study was to compare digital image correlation (DIC) strain measurements to those obtained from strain gages in order to assess the applicability of DIC technology to common biomechanical testing scenarios. METHODS: Compression and bending tests were conducted on aluminum alloy, polyurethane foam, and laminated polyurethane foam specimens. Simplified single-legged stance loads were applied to composite and cadaveric femurs. RESULTS: Results showed no significant differences in principal strain values (or variances) between strain gage and DIC measurements on the aluminum alloy and laminated polyurethane foam specimens. There were significant differences between the principal strain measurements of the non-laminated polyurethane foam specimens, but the deviation from theoretical results was similar for both measurement techniques. DIC and strain gage data matched well in 83.3% of all measurements in composite femur models and in 58.3% of data points in cadaveric specimens. Increased variation in cadaveric data was expected, and is associated with the well-documented variability of strain gage analysis on hard tissues as a function of bone temperature, hydration, gage protection, and other factors specific to cadaveric biomechanical testing. CONCLUSIONS: DIC techniques provide similar results to those obtained from strain gages across standard and anatomical specimens while providing the advantages of reduced specimen preparation time and full-field data analysis.

Characterization of Femoral Component Initial Stability and Cortical Strain in a Reduced Stem-Length Design.

BACKGROUND: Short-stemmed femoral components facilitate reduced exposure surgical techniques while preserving native bone. A clinically successful stem should ideally reduce risk for stress shielding while maintaining adequate primary stability for biological fixation. We asked (1) how stem-length changes cortical strain distribution in the proximal femur in a fit-and-fill geometry and (2) if short-stemmed components exhibit primary stability on par with clinically successful designs. METHODS: Cortical strain was assessed via digital image correlation in composite femurs implanted with long, medium, and short metaphyseal fit-and-fill stem designs in a single-leg stance loading model. Strain was compared to a loaded, unimplanted femur. Bone-implant micromotion was then compared with reduced lateral shoulder short stem and short tapered-wedge designs in cyclic axial and torsional testing. RESULTS: Femurs implanted with short-stemmed components exhibited cortical strain response most closely matching that of the intact femur model, theoretically reducing the potential for proximal stress shielding. In micromotion testing, no difference in primary stability was observed as a function of reduced stem length within the same component design. CONCLUSION: Our findings demonstrate that within this fit-and-fill stem design, reduction in stem length improved proximal cortical strain distribution and maintained axial and torsional stability on par with other stem designs in a composite femur model. Short-stemmed implants may accommodate less invasive surgical techniques while facilitating more physiological femoral loading without sacrificing primary implant stability.

Hydrogen Production and Enzyme Activities in the Hyperthermophile Thermococcus paralvinellae Grown on Maltose, Tryptone, and Agricultural Waste.

Thermococcus may be an important alternative source of H2 in the hot subseafloor in otherwise low H2 environments such as some hydrothermal vents and oil reservoirs. It may also be useful in industry for rapid agricultural waste treatment and concomitant H2 production. Thermococcus paralvinellae grown at 82°C without sulfur produced up to 5 mmol of H2 L(-1) at rates of 5-36 fmol H2 cell(-1) h(-1) on 0.5% (wt vol(-1)) maltose, 0.5% (wt vol(-1)) tryptone, and 0.5% maltose + 0.05% tryptone media. Two potentially inhibiting conditions, the presence of 10 mM acetate and low pH (pH 5) in maltose-only medium, did not significantly affect growth or H2 production. Growth rates, H2 production rates, and cell yields based on H2 production were the same as those for Pyrococcus furiosus grown at 95°C on the same media for comparison. Acetate, butyrate, succinate, isovalerate, and formate were also detected as end products. After 100 h, T. paralvinellae produced up to 5 mmol of H2 L(-1) of medium when grown on up to 70% (vol vol(-1)) waste milk from cows undergoing treatment for mastitis with the bacterial antibiotic Ceftiofur and from untreated cows. The amount of H2 produced by T. paralvinellae increased with increasing waste concentrations, but decreased in P. furiosus cultures supplemented with waste milk above 1% concentration. All mesophilic bacteria from the waste milk that grew on Luria Bertani, Sheep's Blood (selective for Staphylococcus, the typical cause of mastitis), and MacConkey (selective for Gram-negative enteric bacteria) agar plates were killed by heat during incubation at 82°C. Ceftiofur, which is heat labile, was below the detection limit following incubation at 82°C. T. paralvinellae also produced up to 6 mmol of H2 L(-1) of medium when grown on 0.1-10% (wt vol(-1)) spent brewery grain while P. furiosus produced < 1 mmol of H2 L(-1). Twelve of 13 enzyme activities in T. paralvinellae showed significant (p < 0.05) differences across six different growth conditions; however, methyl viologen-dependent membrane hydrogenase activity remained constant across all media types. The results demonstrate the potential of at least some Thermococcus species to produce H2 if protein and α-glucosides are present as substrates.

Thermococcus paralvinellae sp. nov. and Thermococcus cleftensis sp. nov. of hyperthermophilic heterotrophs from deep-sea hydrothermal vents.

Two heterotrophic hyperthermophilic strains, ES1(T) and CL1(T), were isolated from Paralvinella sp. polychaete worms collected from active hydrothermal vent chimneys in the north-eastern Pacific Ocean. Both were obligately anaerobic and produced H2S in the presence of elemental sulfur and H2. Complete genome sequences are available for both strains. Phylogenetic analyses based on 16S rRNA gene sequences showed that the strains are more than 97% similar to most other species of the genus Thermococcus. Therefore, overall genome relatedness index analyses were performed to establish that these strains are novel species. For each analysis, strain ES1(T) was determined to be most similar to Thermococcus barophilus MP(T), while strain CL1(T) was determined to be most similar to Thermococcus sp. 4557. The average nucleotide identity scores for these strains were 84% for strain ES1(T) and 81% for strain CL1(T), genome-to-genome direct comparison scores were 23% for strain ES1(T) and 47% for strain CL1(T), and the species identification scores were 89% for strain ES1(T) and 88% for strain CL1(T). For each analysis, strains ES1(T) and CL1(T) were below the species delineation cut-off. Therefore, based on their whole genome sequences, strains ES1(T) and CL1(T) are suggested to represent novel species of the genus Thermococcus for which the names Thermococcus paralvinellae sp. nov. and Thermococcus cleftensis sp. nov. are proposed, respectively. The type strains are ES1(T) ( =DSM 27261(T) =KACC 17923(T)) and CL1(T) ( =DSM 27260(T) =KACC 17922(T)).

Complete genome sequence of hyperthermophilic archaeon Thermococcus sp. ES1.

Thermococcus sp. strain ES1 is an anaerobic, hyperthermophilic archaeon from a hydrothermal vent that catabolizes sugars and peptides and produces H2S from S°, H2, acetate and CO2 as its primary metabolites. We present the complete genome sequence of this strain (1,957,742bp) with a focus on its substrate utilization and metabolite production capabilities. The sequence will contribute to the development of heterotrophic archaea for bioenergy production and biogeochemical modeling in hydrothermal environments.

Airway pressure release ventilation in morbidly obese surgical patients with acute lung injury and acute respiratory distress syndrome.

Morbidly obese patients with body mass index greater than 40 kg/m(2) and respiratory failure requiring critical care services are increasingly seen in trauma and acute care surgical centers. Baseline respiratory pathophysiology including decreased pulmonary compliance with dependent atelectasis and abnormal ventilation-perfusion relationships predisposes these patients to acute lung injury (ALI) and adult respiratory distress syndrome (ARDS) as well as prolonged stays in the intensive care unit. Airway pressure release ventilation (APRV) is an increasingly used alternative mode for salvage therapy in patients with hypoxemic respiratory failure that also provides lung protection from ventilator-induced lung injury. APRV provides the conceptual advantage of an "open lung" approach to ventilation that may be extended to the morbidly obese patient population with ALI and ARDS. We discuss the theoretical benefits and a recent clinical experience of APRV ventilation in the morbidly obese patient with respiratory failure at a Level I trauma, surgical critical care, and acute care surgery center.

Electrosynthesis of organic compounds from carbon dioxide is catalyzed by a diversity of acetogenic microorganisms.

Microbial electrosynthesis, a process in which microorganisms use electrons derived from electrodes to reduce carbon dioxide to multicarbon, extracellular organic compounds, is a potential strategy for capturing electrical energy in carbon-carbon bonds of readily stored and easily distributed products, such as transportation fuels. To date, only one organism, the acetogen Sporomusa ovata, has been shown to be capable of electrosynthesis. The purpose of this study was to determine if a wider range of microorganisms is capable of this process. Several other acetogenic bacteria, including two other Sporomusa species, Clostridium ljungdahlii, Clostridium aceticum, and Moorella thermoacetica, consumed current with the production of organic acids. In general acetate was the primary product, but 2-oxobutyrate and formate also were formed, with 2-oxobutyrate being the predominant identified product of electrosynthesis by C. aceticum. S. sphaeroides, C. ljungdahlii, and M. thermoacetica had high (>80%) efficiencies of electrons consumed and recovered in identified products. The acetogen Acetobacterium woodii was unable to consume current. These results expand the known range of microorganisms capable of electrosynthesis, providing multiple options for the further optimization of this process.