Extrahepatic perfusion and incomplete hepatic perfusion after hepatic arterial infusion pump implantation: incidence and clinical implications.

INTRODUCTION: This study investigates the incidence of extrahepatic perfusion and incomplete hepatic perfusion at intraoperative methylene blue testing and on postoperative nuclear imaging in patients undergoing hepatic arterial infusion pump (HAIP) chemotherapy. METHODS: The first 150 consecutive patients who underwent pump implantation in the Netherlands were included. All patients underwent surgical pump implantation with the catheter in the gastroduodenal artery. All patients underwent intraoperative methylene blue testing and postoperative nuclear imaging (99mTc-Macroaggregated albumin SPECT/CT) to determine perfusion via the pump. RESULTS: Patients were included between January-2018 and December-2021 across eight centers. During methylene blue testing, 29.3% had extrahepatic perfusion, all successfully managed intraoperatively. On nuclear imaging, no clinically relevant extrahepatic perfusion was detected (0%, 95%CI: 0.0-2.5%). During methylene blue testing, 2.0% had unresolved incomplete hepatic perfusion. On postoperative nuclear imaging, 8.1% had incomplete hepatic perfusion, leading to embolization in only 1.3%. CONCLUSION: Methylene blue testing during pump placement for intra-arterial chemotherapy identified extrahepatic perfusion in 29.3% of patients, but could be resolved intraoperatively in all patients. Postoperative nuclear imaging found no clinically relevant extrahepatic perfusion and led to embolization in only 1.3% of patients. The role of routine nuclear imaging after HAIP implantation should be studied in a larger cohort.

Toward the oxidative deconstruction of lignin: oxidation of ß-1 and ß-5 linkages.

There have been numerous reports on methods for the oxidative cleavage of ß-O-4 linkages in lignin model compounds, but relatively few reports of how those methods affect other linkages that are present in lignin. We have investigated the effect of several of these oxidation methods on the ß-1 and the ß-5 lignin linkages, using four ß-1 and ß-5 model compounds. We observed that direct oxidative cleavage of C-C bonds occurs in metal-catalyzed TEMPO oxidation systems and with iron porphyrin oxidations, neither of which had we observed in similar oxidations on ß-O-4 models. The ß-5 linkage proved to be largely resistant to all of these oxidative systems, but the dihydrofuran ring in the ß-5 model 3 was opened when treated with KMnO4 at elevated temperature. Most promising was the oxidation of 2 with DDQ, which produced the benzylic ketone in high yield (84%), as it does in reactions with ß-O-4 models. This reaction exhibits selectivity for the benzylic position as well as compatibility with phenols, characteristics that are highly desirable for a two-step, benzylic oxidation/Baeyer-Villiger route for cleavage of lignin.

Selective cleavage of the C(α)-C(ß) linkage in lignin model compounds via Baeyer-Villiger oxidation.

Lignin is an amorphous aromatic polymer derived from plants and is a potential source of fuels and bulk chemicals. Herein, we present a survey of reagents for selective stepwise oxidation of lignin model compounds. Specifically, we have targeted the oxidative cleavage of Cα-Cß bonds as a means to depolymerize lignin and obtain useful aromatic compounds. In this work, we prepared several lignin model compounds that possess structures, characteristic reactivity, and linkages closely related to the parent lignin polymer. We observed that selective oxidation of benzylic hydroxyl groups, followed by Baeyer-Villiger oxidation of the resulting ketones, successfully cleaves the Cα-Cß linkage in these model compounds.

Hereditary persistence of alpha-fetoprotein mimicking testicular cancer in a patient with acute epididymitis.

Only a few cases of hereditary persistence of α-fetoprotein (HPAFP) have been published. This report presents an association between HPAFP and inflammatory testis disease, to the authors' knowledge, for the first time. HPAFP was diagnosed in a 41-year-old patient with acute epididymitis after exclusion of malignancies and benign diseases.

Utilization of Lignin-Derived Small Molecules: Epoxy Polymers from Lignin Oxidation Products.

Much effort has been invested in developing methods for producing small molecules from lignin as a way to source feedstock chemicals from renewable sources. Significant progress is being made, and methods for deconstructing lignin are producing good yields of small, mononuclear aromatic products-sufficient amounts to enable studies of the potential use of these compounds as replacements for compounds currently produced from petroleum. To investigate the use of lignin products in epoxies, we begin with aromatic acids that can be produced from lignin, treat them with epichlorohydrin to make glycidyl ethers, and investigate the thermal and mechanical properties of cured mixtures of these compounds with a commercial epoxy resin (EPON 826) and an anhydride curing agent (NMA). While most of the lignin-modified epoxy polymers exhibit good physical and thermal properties, the polymer prepared from p-hydroxybenzoic acid (compound 6) has a higher glass-transition temperature (Tg = 159 °C) than do thermosets made with other lignin-derived materials, such as vanillic acid diglycidyl ether (compound 4) and matches the Tg of cured samples of the commercial EPON-826/NMA epoxy system. This is significant, as p-hydroxybenzoic acid is readily available by simple hydrolysis of several different lignins and functions as a drop-in replacement for 50% of the BPA-based material in this commercial system without significant degradation of material properties. The use of lignin-derived small molecules in high-value systems such as epoxies may help improve the economics of biorefineries.

Phase Ib/II trial testing combined radiofrequency ablation and ipilimumab in uveal melanoma (SECIRA-UM).

Approximately, 50% of patients with uveal melanoma develop distant metastasis for which no standard therapy is established. In contrast to cutaneous melanoma, the anti-CTLA-4 antibody ipilimumab showed no clinical activity in uveal melanoma. Liver directed therapies improve local control, but fail to show overall survival (OS) benefit. Preclinical experiments demonstrated that radiofrequency ablation (RFA) induced durable responses in combination with anti-CTLA-4. The aim of this phase Ib/II study was to assess safety and efficacy of RFA plus ipilimumab in uveal melanoma. Patients underwent RFA of one liver lesion and subsequently received four courses ipilimumab 0.3, 3 or 10 mg/kg every 3 weeks in a 3 + 3 design. Primary endpoints were safety in terms of dose limiting toxicities per cohort to define the recommended phase II dose (RP2D) in the phase Ib part and confirmed the objective response rate and disease control rate (DCR) of non-RFA lesions in the phase II part. Secondary endpoints were progression-free survival (PFS) and OS. Ipilimumab 10 mg/kg + RFA was initially defined as the RP2D. However, after 19 patients, the study was amended to adjust the RP2D to ipilimumab 3 mg/kg + RFA, because 47% of patients treated with 10 mg/kg had developed grade 3 colitis. In the 3 mg/kg cohort, also 19 patients have been treated. Immunotherapy-related grade ≥3 adverse events were observed in 53% of patients in the 10 mg/kg cohort versus 32% in the 3 mg/kg cohort. No confirmed objective responses were observed; the confirmed DCR was 5% in the 10 mg/kg cohort and 11% in the 3 mg/kg cohort. Median PFS was 3 months and comparable for both cohorts, median OS was 14.2 months for the 10 mg/kg cohort versus 9.7 months for the 3 mg/kg cohort. Combining RFA with ipilimumab 3 mg/kg was well tolerated, but showed very limited clinical activity in uveal melanoma.

Resectability and Ablatability Criteria for the Treatment of Liver Only Colorectal Metastases: Multidisciplinary Consensus Document from the COLLISION Trial Group.

The guidelines for metastatic colorectal cancer crudely state that the best local treatment should be selected from a 'toolbox' of techniques according to patient- and treatment-related factors. We created an interdisciplinary, consensus-based algorithm with specific resectability and ablatability criteria for the treatment of colorectal liver metastases (CRLM). To pursue consensus, members of the multidisciplinary COLLISION and COLDFIRE trial expert panel employed the RAND appropriateness method (RAM). Statements regarding patient, disease, tumor and treatment characteristics were categorized as appropriate, equipoise or inappropriate. Patients with ECOG≤2, ASA≤3 and Charlson comorbidity index ≤8 should be considered fit for curative-intent local therapy. When easily resectable and/or ablatable (stage IVa), (neo)adjuvant systemic therapy is not indicated. When requiring major hepatectomy (stage IVb), neo-adjuvant systemic therapy is appropriate for early metachronous disease and to reduce procedural risk. To downstage patients (stage IVc), downsizing induction systemic therapy and/or future remnant augmentation is advised. Disease can only be deemed permanently unsuitable for local therapy if downstaging failed (stage IVd). Liver resection remains the gold standard. Thermal ablation is reserved for unresectable CRLM, deep-seated resectable CRLM and can be considered when patients are in poor health. Irreversible electroporation and stereotactic body radiotherapy can be considered for unresectable perihilar and perivascular CRLM 0-5cm. This consensus document provides per-patient and per-tumor resectability and ablatability criteria for the treatment of CRLM. These criteria are intended to aid tumor board discussions, improve consistency when designing prospective trials and advance intersociety communications. Areas where consensus is lacking warrant future comparative studies.

Inter-observer agreement for abdominal CT in unselected patients with acute abdominal pain.

The level of inter-observer agreement of abdominal computed tomography (CT) in unselected patients presenting with acute abdominal pain at the Emergency Department (ED) was evaluated. Two hundred consecutive patients with acute abdominal pain were prospectively included. Multi-slice CT was performed in all patients with intravenous contrast medium only. Three radiologists independently read all CT examinations. They recorded specific radiological features and a final diagnosis on a case record form. We calculated the proportion of agreement and kappa values, for overall, urgent and frequently occurring diagnoses. The mean age of the evaluated patients was 46 years (range 19-94), of which 54% were women. Overall agreement on diagnoses was good, with a median kappa of 0.66. Kappa values for specific urgent diagnoses were excellent, with median kappa values of 0.84, 0.90 and 0.81, for appendicitis, diverticulitis and bowel obstruction, respectively. Abdominal CT has good inter-observer agreement in unselected patients with acute abdominal pain at the ED, with excellent agreement for specific urgent diagnoses as diverticulitis and appendicitis.

Fitz-Hugh-Curtis syndrome resulting in nutmeg liver on computed tomography.

A 34-year-old woman entered the emergency room with abdominal pain in the right upper quadrant. Computed tomography scan showed a nutmeg liver suspected for increased venous pressure by thrombosis of the liver veins, Budd-Chiari malformation, or right-sided heart failure. Interestingly, the diagnosis was pelvic inflammatory disease complicated by the Fitz-Hugh-Curtis syndrome (FHCS). Pelvic inflammatory disease resulted from an ascended infection by Chlamydia trachomatis. FHCS was caused by perihepatitis defined as inflammation of the peritoneal capsule of the liver. Fast diagnosis and treatment is crucial. Therefore, we report a case of FHCS characterized by a nutmeg liver on computed tomography.

Diamagnetic current measurements in a solid-state plasma.

Using a resonant structure, we have established large pressure gradients in a magnetized indium antimonide (InSb) plasma. This produces diamagnetic current in the milliampere range. The magnetic field generated by the current is sensed with a small magnetic coil. The operating frequency is about 230 kHz with a power level on the order of 100 mW. The InSb is magnetized with a 1 T magnetic field produced with permanent magnets. We show good agreement between our experimental measurements and the expected diamagnetic current.

Life-threatening acute and chronic thromboembolic pulmonary hypertension and subclavian vein thrombosis.

Severe thromboembolic pulmonary hypertension is an infrequent but potentially fatal complication of effort thrombosis (Paget-Schroetter syndrome) of the upper extremity. It has been sporadically reported in the literature, but in most cases has affected young, otherwise healthy athletes. Because this syndrome has been rarely described, it is likely underdiagnosed, and optimal evaluation and treatment has not been established. We describe three young athletic persons who developed thrombosis of the subclavian vein after repetitive motion of the upper extremity, and in whom life-threatening pulmonary hypertension resulted from acute and chronic pulmonary emboli. We then review the mechanism, clinical presentation, diagnosis, and available therapeutic modalities.

Resonant transducers for solid-state plasma density modulation.

We have developed transducers capable of modulating the plasma density and plasma density gradients in indium antimonide. These transducers make use of piezoelectric drivers to excite acoustic pressure resonance at 3λ/2, generating large amplitude standing waves and plasma density modulations. The plasma density has been directly measured using a laser diagnostic. A layered media model shows good agreement with the experimental measurements.

Da Vinci© Skills Simulator™: is an early selection of talented console surgeons possible?

To investigate whether the learning curve of robotic surgery simulator training depends on the probands' characteristics, such as age and prior experience, we conducted a study of six distinct proband groups, using the da Vinci Skills Simulator: experienced urological robotic surgeons, surgeons with experience as da Vinci tableside assistants, urological surgeons with laparoscopic experience, urological surgeons without laparoscopic experience, and complete novices aged 25 and younger and 40 and older. The results showed that all experienced robotic surgeons reached expert level (>90 %, as defined previously in the literature) within the first three repetitions and remained on a high level of performance. All other groups performed worse. Tableside assistants, laparoscopically experienced surgeons, and younger novices showed a better performance in all exercises than surgeons without laparoscopic experience and older novices. A linear mixed-effects model analysis demonstrated no significant difference in learning curves between proband groups in all exercises except the RW1 exercise for the younger proband group. In summary, we found that performance in robotic surgery, measured by performance scores in three virtual simulator modules using the EndoWrist techniques, was dependent on age and prior experience with robotic and laparoscopic surgery. However, and most importantly, the learning curve was not significantly affected by these factors. This suggests that the da Vinci Skills Simulator™ is a useful practice tool for everyone learning or performing robotic surgery, and that early selection of talented surgeons is neither possible nor necessary.

Spectral sensing for tissue diagnosis during lung biopsy procedures: The importance of an adequate internal reference and real-time feedback.

OBJECTIVES: Difficulties in obtaining a representative tissue sample are a major obstacle in timely selecting the optimal treatment for patients with lung cancer or other malignancies. Having a modality to provide needle guidance and confirm the biopsy site selection could be of great clinical benefit, especially when small masses are targeted. The objective of this study was to evaluate whether diffuse reflectance spectroscopy (DRS) at the tip of a core biopsy needle can be used for biopsy site confirmation in real time, thereby enabling optimized biopsy acquisition and improving diagnostic capability. MATERIALS AND METHODS: We included a total of 23 patients undergoing a routine computed tomography (CT) guided transthoracic needle biopsy of a lesion suspected for lung cancer or metastatic disease. DRS measurements were acquired during needle insertion and clinically relevant parameters were extracted from the spectral data along the needle paths. Histopathology results were compared with the DRS data at the final measurement position. RESULTS: Analysis of the collective data acquired from all enrolled subjects showed significant differences (p<0.01) for blood content, stO2, water content, and scattering amplitude. The identified spectral contrast matched the final pathology in 20 out of 22 clinical cases that could be used for analysis, which corresponds with an overall diagnostic performance of 91%. Three cases underlined the importance of adequate reference measurements and the need for real time diagnostic feedback. Continuous real time DRS measurements performed during a biopsy procedure in one patient provided clear information with respect to the variation in tissue and allowed identification of the tumour boundary. CONCLUSIONS: The presented technology creates a basis for the design and clinical implementation of integrated fibre-optic tools for a variety of minimal invasive applications.

In vivo characterization of colorectal metastases in human liver using diffuse reflectance spectroscopy: toward guidance in oncological procedures.

There is a strong need to develop clinical instruments that can perform rapid tissue assessment at the tip of smart clinical instruments for a variety of oncological applications. This study presents the first in vivo real-time tissue characterization during 24 liver biopsy procedures using diffuse reflectance (DR) spectroscopy at the tip of a core biopsy needle with integrated optical fibers. DR measurements were performed along each needle path, followed by biopsy of the target lesion using the same needle. Interventional imaging was coregistered with the DR spectra. Pathology results were compared with the DR spectroscopy data at the final measurement position. Bile was the primary discriminator between normal liver tissue and tumor tissue. Relative differences in bile content matched with the tissue diagnosis based on histopathological analysis in all 24 clinical cases. Continuous DR measurements during needle insertion in three patients showed that the method can also be applied for biopsy guidance or tumor recognition during surgery. This study provides an important validation step for DR spectroscopy-based tissue characterization in the liver. Given the feasibility of the outlined approach, it is also conceivable to make integrated fiber-optic tools for other clinical procedures that rely on accurate instrument positioning.

Real-time In Vivo Tissue Characterization with Diffuse Reflectance Spectroscopy during Transthoracic Lung Biopsy: A Clinical Feasibility Study.

PURPOSE: This study presents the first in vivo real-time tissue characterization during image-guided percutaneous lung biopsies using diffuse reflectance spectroscopy (DRS) sensing at the tip of a biopsy needle with integrated optical fibers. EXPERIMENTAL DESIGN: Tissues from 21 consented patients undergoing lung cancer surgery were measured intraoperatively using the fiber-optic platform capable of assessing various physical tissue properties highly correlated to tissue architecture and composition. In addition, the method was tested for clinical use by performing DRS tissue sensing during 11 routine biopsy procedures in patients with suspected lung cancer. RESULTS: We found that water content and scattering amplitude are the primary discriminators for the transition from healthy lung tissue to tumor tissue and that the reliability of these parameters is not affected by the amount of blood at the needle tip. In the 21 patients measured intraoperatively, the water-to-scattering ratio yielded a 56% to 81% contrast difference between tumor and surrounding tissue. Analysis of the 11 image-guided lung biopsy procedures showed that the tissue diagnosis derived from DRS was diagnostically discriminant in each clinical case. CONCLUSIONS: DRS tissue sensing integrated into a biopsy needle may be a powerful new tool for biopsy guidance that can be readily used in routine diagnostic lung biopsy procedures. This approach may not only help to increase the successful biopsy yield for histopathologic analysis, but may also allow specific sampling of vital tumor tissue for genetic profiling.

The new definition of myocardial infarction: diagnostic and prognostic implications in patients with acute coronary syndromes.

BACKGROUND: The clinical implications of the recently revised criteria for diagnosis of acute myocardial infarction (AMI) in patients with suspected acute coronary syndromes are unknown. METHODS: To evaluate the prognostic implications of the new diagnostic criteria for AMI, we studied 493 consecutive patients with suspected acute coronary syndromes admitted to University of Michigan, Ann Arbor, between May 1, 1999, and January 1, 2000. Patients with positive cardiac enzymes and symptoms suggestive of coronary ischemia (n = 275) were divided into 2 groups: group A, with elevated peak creatine kinase-MB fraction and/or new electrocardiographic changes suggestive of AMI regardless of troponin status (diagnosed as AMI by old criteria), and group B, with normal peak creatine kinase-MB fraction but elevated troponin I level (additional patients diagnosed as having AMI by new criteria). RESULTS: As compared with group A (n = 224), patients in group B (n = 51) were older women, with increased comorbidities such as previous stroke or aortic stenosis, and had fewer in-hospital procedures. In-hospital adverse events (reinfarction, heart failure, shock, and mortality) were similar between the groups, whereas 6-month mortality was higher among group B patients (16.3% vs 5.8%; P =.03). This difference was not statistically significant after adjustment for differences in baseline characteristics between the groups (odds ratio, 1.6; 95% confidence interval, 0.5-5.9). CONCLUSIONS: The new criteria result in a substantial increase in the diagnosis of AMI. Furthermore, they help to identify patients with acute coronary syndromes who have greater comorbidities and worse 6-month outcomes who are otherwise missed by the old criteria. Additional studies are needed to confirm these preliminary findings and to determine the financial implications of the new criteria.

Intramolecular Excited State Electronic Coupling Along an alpha-Helical Peptide.

Several families of peptides composed of alternating L-alanine (Ala) and alpha-aminoisobutyric acid (Aib) residues with an appended N,N-dimethylanilino and/or 2-naphthalenyl group exist in MeOH and CDCl(3) as alpha-helices. Steady state and time-resolved fluorescence measurements show that the distance and dihedral angle between the appended donor and acceptor and the alignment of the vectors for intramolecular charge transfer interaction (from donor to acceptor) with or against that of the helical dipole moment significantly influence the efficiency of photoinduced electronic coupling and, hence, of intramolecular fluorescence quenching.

Low frequency pressure modulation of indium antimonide.

A lumped parameter resonator capable of generating megapascal pressures at low frequency (kilohertz) is described. Accelerometers are used to determine the applied pressure, and are calibrated with a piezoelectric sample. A laser diagnostic was also developed to measure the pressure in semiconductor samples through the band gap pressure dependence. In addition, the laser diagnostic has been used to measure the attenuation coefficient α of commercially available indium antimonide (InSb) wafers. The resonator and laser diagnostic have been used with InSb samples to verify the pressure response.