Cancer of unknown primary (CUP) through the lens of precision oncology: a single institution perspective.

PURPOSE: For patients with cancer of unknown primary (CUP), treatment options are limited. Precision oncology, the interplay of comprehensive genomic profiling (CGP) and targeted therapies, aims to offer additional treatment options to patients with advanced and hard-to-treat cancers. We aimed to highlight the use of a molecular tumor board (MTB) in the therapeutic management of CUP patients. METHODS: In this single-center observational study, CUP patients, presented to the MTB of the Comprehensive Cancer Center Munich LMU, a tertiary care center, were analyzed retrospectively. Descriptive statistics were applied to describe relevant findings. RESULTS: Between June 2016 and February 2022, 61 patients with unfavorable CUP were presented to the MTB, detected clinically relevant variants in 74% (45/61) of patients, of which 64% (29/45) led to therapeutic recommendation. In four out of 29 patients (14%), the treatment recommendations were implemented, unfortunately without resulting in clinical benefit. Reasons for not following the therapeutic recommendation were mainly caused by the physicians' choice of another therapy (9/25, 36%), especially in the context of worsening of general condition, lost to follow-up (7/25, 28%) and death (6/25, 24%). CONCLUSION: CGP and subsequent presentation to a molecular tumor board led to a high rate of therapeutic recommendations in patients with CUP. Recommendations were only implemented at a low rate; however, late GCP diagnostic and, respectively, MTB referral were found more frequent for the patients with implemented treatment. This contrast underscores the need for early implementation of CGP into the management of CUP patients.

Peripherally inserted central catheters in an acute-care hospital.

BACKGROUND: Peripherally inserted central catheterization is a relatively new approach for intravenous therapy in acute-care hospitals. Few studies are available on peripherally inserted central catheters (PICCs) used in adult patients in an acute-care setting. We examine the natural history and outcome of PICC use in our hospital. METHODS: A retrospective review was undertaken of all hospitalized patients who had PICCs inserted in an acute-care, metropolitan teaching hospital for any reason from July 1991 through July 1992. Patients who had PICCs inserted, used, and then removed in the same hospitalization were evaluated. RESULTS: A total of 135 PICCs were inserted in 114 patients. Six PICCs (4.4%) were inserted in intensive care unit settings and 129 (95.6%) in general medical or surgical service. The mean duration catheters were in place before removal was 14.1 days. Sixty-three catheters (46.7%) were removed following completion of therapy. The rate of PICC-related infection was 2.2% (three catheters). The occlusion rate was higher for 20-gauge catheters (18.4%) than for 18-gauge catheters (8.2%) (P = .08). When the rate of complications was compared as a function of catheter use (total parenteral nutrition vs any other use), there was no statistically significant difference (P = .12). Overall complications related to catheter insertion and removal were uncommon. CONCLUSIONS: Based on our study, we conclude that the PICC provides a reasonable and safe alternative to other centrally placed venous devices. In addition, the convenience of maintaining a PICC compared with peripheral intravenous access makes this an attractive method for in-hospital use.

In vitro and in vivo characterization of avian reoviruses. III. Host factors affecting virulence and persistence.

Three avian reovirus isolates (2177, 2035, and 1733) were used to determine the effect of the age of chickens at inoculation on virus virulence and persistence. Groups of specific-pathogen-free leghorns were inoculated with three different reovirus isolates of different levels of pathogenicity at 1 day, 1 week, 2 weeks, 3 weeks, or 4 weeks of age. Tissues were examined for the presence of virus and lesions at regular intervals until 8 weeks postinoculation (PI) and then again at 22 weeks PI. Isolate 1733, which is highly pathogenic, was reisolated from the thymus, trachea, liver, intestine, cecal tonsils, bursa of Fabricius, gastrocnemius tendon, and white blood cells. Microscopic lesions were observed in some tissues, including the thymus, liver, spleen, bursa of Fabricius, and gastrocnemius tendons, when sampled within a 7-day period following inoculation. This isolate persisted and produced microscopic lesions in the gastrocnemius tendons for as long as 22 weeks PI. The isolates of intermediate pathogenicity (2035) or low pathogenicity (2177) were isolated less frequently and from fewer tissues than isolate 1733. Isolate 2035 could be found in the gastrocnemius tendons as long as 7 weeks PI, whereas isolate 2177 was never isolated from the tendons, nor did it produce any notable gross or microscopic tissue changes. Birds inoculated at age 1 week or older with any of the three reovirus pathotypes were more resistant to infection than 1-day-old inoculates, as evidenced by a decrease in virus reisolations and a concurrent reduction in the severity of lesions in selected tissues.

Amalgam and composite resin as an alternative to crown and bridgework in the rehabilitation of an extensively debilitated dentition. Case report.

A less expensive alternative to alloy-ceramic crown and bridgework is presented. The aetiology and effects of the extensively debilitated dentition and a treatment rationale are briefly reviewed. A report of the technique and the result of one clinical case then follows.

The effect of gold coating agents on residual stress in alloy-ceramic specimens.

The use of gold coating agents has been claimed to reduce residual stress in alloy-ceramic composites. The purpose of this study was to evaluate the efficacy of gold coating agents in preventing cracking of bonded porcelain. Residual stress in alloy-ceramic specimens could be increased by decreasing the coefficient of thermal expansion (alpha) of the porcelain. Vitadur-N porcelain (jacket crown type, low alpha) was mixed in increasing proportions with VMK porcelain (high alpha) to prepare five test blends with decreasing values for alpha. For each test blend, alpha was measured by means of a vitreous silica dilatometer, and varied from 13.6 x 10(-6)/K to 11.0 x 10(-6)/K. The test blends were fused around spherical specimens of a substrate alloy, Option (alpha = 14.0 x 10(-6)/K), both with and without the use of three gold coating agents, Wilkote, Spectra-Seal and Deck-Gold (normal). The composite spheres were examined under 20 x magnification after 24 hours and again after eight weeks for evidence of cracking. There was no significant difference in the failure rate of the alloy-ceramic specimens with or without any of the gold coating agents. In a bonding porcelain, alpha can be lowered in a controlled manner by the addition of varying amounts of jacket crown porcelain. Cracking of the ceramic coating occurred at and above an alpha mismatch of 1.8 x 10(-6)/K. Gold coating agents have an insignificant effect on residual stress in alloy-ceramic specimens.

A management approach for temporomandibular disorders.

Conservative, non invasive and reversible treatment is possible and highly successful for most temporomandibular disorder patients. Unfortunately, at this time it is not possible to provide preventive therapy or predict an 'at risk' group. Perpetuating and aggravating factors can sometimes be identified and eliminated in patients suffering from a TMD. TMD treatment can also be of benefit for chronic headache patients. A logical approach to the management of TMJ disorders has been outlined that emphasises the principle of 'escalation of therapy'. This has the advantage of avoiding overtreatment and maintaining patient confidence if initial attempts fail.

Strategies for complete denture success: beyond technical excellence.

Many patients are quite satisfied with dentures that are extremely poor, while other patients are dissatisfied with dentures that are technically excellent. Overall, some 25% of patients are likely to be dissatisfied with their artificial teeth. This article addresses the aspects of denture success not covered by technical considerations. The strategies are based on the principles of good communication and involve an understanding and respect for patients' motivations in wearing dentures. The strategies include help in the development of neuromuscular control and in training regarding mastication. Most importantly, they emphasize patient involvement in the development of the denture. Patients must be made aware of their responsibilities in achieving a satisfactory outcome in the complex patient/denture relationship.

Aetiology and management of the anterior dislocated disc. Management of articular disc displacement.

There is considerable disagreement among clinicians regarding the appropriate management of articular disc displacement. Research findings are difficult to interpret and compare because of the multitude of clinical variables. A number of questions remain unanswered. Is articular disc displacement truly pathology? Is diagnosis by clinical signs and symptoms adequate and accurate? Do we need to 'reposition' the disc and, if so, can we? Is reciprocal clicking a reliable sign of disc displacement and does it require treatment in the absence of other signs and symptoms? This article presents a short review of the more recent literature and provides guidelines for appropriate treatment.

Diesel particle mass concentration by optical techniques.

Particle mass concentrations in the exhaust streams of a variety of Diesel engines have been measured using both a visible wavelength opacity meter and an IR photoacoustic device. We present real-time recordings of the emissions from vehicles operated over the Federal Test Procedure driving cycle. Steady-state mass concentrations of a few mg x m(-3) can be measured by opacity and as low as 0.4 mg x m(-3) by the photoacoustic technique, but the uncertainty is approximately 15% in both cases. An uncertainty of approximately 20% is found in the estimation of total mass emission rates over the Federal Test Procedure cycle by integration of the optical signals.

Craniomandibular disorders: a controversy.

Clinical opinion varies greatly regarding the factors involved in craniomandibular disorders. Occlusion, trauma, cervical problems, orthodontic therapy and internal derangements are often cited as major factors. An examination of current research is provided to see if this is justified.

Photoacoustic determination of optical absorption to extinction ratio in aerosols.

The photoacoustic technique has been used in conjunction with an optical transmission measurement to determine the fraction of light absorbed in cigarette and acetylene smoke aerosols. At 0.5145-microm wavelength,the absorption-to-extinction fraction is 0.01 +/- 0.003 for cigarette smoke and is in excellent agreement with predictions from Mie theory for smoke particles having a refractive index of 1.45-0.00133i and a median diameter in the 0.15-0.65-microm range. For acetylene smoke the absorbed fraction was 0.85 +/- 0.05.

Opacity of black smoke: calculated variation with particle size and refractive index.

The opacity of a black smoke (an aerosol of carbon spheres) is calculated from the Mie theory for several lognormal particle distributions. Calculations are presented at a wavelength of 0.55 Am for particle geometric mean diameters in the 10(-3)-1-microm range and geometric mean standard deviations in the 0 (monodisperse) to 0.4 range. For-a given mass concentration the extinction coefficient and, therefore, the opacity can vary by a factor of 2 or more as the size distribution is varied. For absorptive indexes (m(2)) near 0.7, typical of carbon, the smoke opacity is only weakly dependent on the real part of the particle refractive index.

Carbon aerosol visibility vs particle size distribution.

The optical properties of an aerosol of given mass concentration are derived from Mie theory. The visibility is calculated, via the optical extinction coefficient, for several log-normal distributions of carbon particles. Normalizing the optical cross sections of particles by their mass allows clear identification of the diameters at which scattering, absorption, and extinction are greatest. For highly absorbing particles this occurs in the 0.15-0.5-lambda diameter range.

Heterogeneity of BmpA (P39) among European isolates of Borrelia burgdorferi sensu lato and influence of interspecies variability on serodiagnosis.

The molecular and antigenic variabilities of BmpA (P39) among European isolates of Borrelia burgdorferi were analyzed. The bmpA sequences of 12 isolates representing all three species of B. burgdorferi sensu lato pathogenic for humans were amplified by PCR, cloned, and sequenced. The BmpA protein of Borrelia garinii is heterogeneous, with an amino acid sequence identity ranging from 91 to 97%, whereas the BmpA proteins of Borrelia afzelii and B. burgdorferi sensu stricto strains appear to be highly conserved (>98.5% intraspecies identity). The interspecies identities ranged from 86 to 92%. Cluster analysis of BmpA reflected the subdivision of B. burgdorferi sensu lato isolates into the three species as well as a considerable heterogeneity among B. garinii strains. The BmpA protein of each species of B. burgdorferi sensu lato was recombinantly expressed in Escherichia coli, purified, and used to generate monoclonal antibodies. Seven BmpA-specific antibodies were identified; six of them recognized conserved epitopes of all three species, whereas one was specific for BmpA of B. afzelii and B. garinii. A monoclonal antibody (H1141) recommended by the Centers for Disease Control and Prevention for use in the standardization of immunoblots showed strong reactivity with BmpA of B. burgdorferi sensu stricto but no or only weak reactivity with BmpA of B. garinii and B. afzelii, respectively. Sera from 86 European patients with Lyme borreliosis in different stages and 73 controls were tested in immunoglobulin G (IgG) and IgM immunoblots with the recombinant BmpA proteins of the three species, revealing specificities of 98.6 to 100%. IgM antibodies against recombinant BmpA were only rarely detected (1.1 to 8.1%). With the BmpA proteins of B. afzelii and B. garinii, sensitivities for the IgG test (sera from stages I to III) were 36.0 and 34.9%, respectively, in contrast to 13.9% with BmpA of B. burgdorferi sensu stricto. Therefore, we recommend that recombinant BmpA of B. afzelii or B. garinii should be used solely, or in addition to B. burgdorferi sensu stricto BmpA, in serodiagnostic tests for Lyme borreliosis in Europe.

Optical absorption by randomly oriented carbon spheroids.

The optical properties of carbon spheroids are compared with those of carbon spheres for all size regimes. In general, the absorption cross section/unit volume is increased by axial elongation, particularly away from the resonance region. The results are specific to carbon since the effect of shape change in a given size regime can depend crucially on the value of the refractive index.