Successful treatment of chronic hepatitis C infection with crushed elbasvir/grazoprevir administered via a percutaneous endoscopic gastrostomy tube.

WHAT IS KNOWN AND OBJECTIVE: Elbasvir/grazoprevir is an all-oral regimen approved for patients with hepatitis C virus (HCV) genotypes 1 and 4, and in renal insufficiency. However, to date, no data exist on the efficacy of this regimen when it is crushed and administered through a percutaneous endoscopic gastrostomy (PEG) tube. Here, we illustrate the case of a 63-year-old man who is the only known patient with HCV infection in the English literature to have successfully achieved a sustained viral response (SVR) when elbasvir/grazoprevir oral combination was administered through a PEG tube. CASE SUMMARY: A 63-year-old man with worsening HCV-associated membranoproliferative glomerulonephritis was referred to the gastroenterology clinic for prompt HCV treatment. He had history of high-grade mucoepidermoid carcinoma of the parotid status post-resection and was expected to develop severe mucositis and dysphagia during radiation precluding typical oral therapy of his HCV. He received a PEG tube for nutrition and underwent a 16 week course of crushed Elbasvir/Grazoprevir for HCV treatment through the PEG. At the end of the therapy he achieved SVR and his kidney function also improved. WHAT IS NEW AND CONCLUSION: We present the first known clinical case of a non-cirrhotic patient with HCV genotype 1A with HCV-related MPGN treated successfully with crushed Elbasvir/Grazoprevir administered through a PEG tube. With the prevalence of PEG tube insertion and HCV on a rise, we expect these 2 population cohorts to intersect in the future. Our report may serve as a guidance in such clinical scenario.

Redistribution of joint moments is associated with changed plantar pressure in diabetic polyneuropathy.

BACKGROUND: Patients with diabetic polyneuropathy (DPN) are often confronted with ulceration of foot soles. Increased plantar pressure under the forefoot has been identified as a major risk factor for ulceration. This study sets out to test the hypothesis that changes in gait characteristics induced by DPN related muscle weakness are the origin of the elevated plantar pressures. METHODS: Three groups of subjects participated: people diagnosed with diabetes without polyneuropathy (DC), people diagnosed with diabetic polyneuropathy (DPN) and healthy, age-matched controls (HC). In all subjects isometric strength of plantar and dorsal flexors was assessed. Moreover, joint moments at ankle, knee and hip joints were determined while walking barefoot at a velocity of 1.4 m/s. Simultaneously plantar pressure patterns were measured. RESULTS: Compared to HC-subjects, DPN-participants walked with a significantly increased internal plantar flexor moment at the first half of the stance phase. Also in DPN-subjects the maximal braking and propelling force applied to the floor was decreased. Moreover, in DPN-subjects the ratio of forefoot-to-rear foot plantar pressures was increased. Body-mass normalized strength of dorsal flexors showed a trend to be reduced in people with diabetes, both DC and DPN, compared to HC-subjects. Plantar flexors tended to be less weak in DC compared to HC and in DPN relative to DC. CONCLUSION: The results of this study suggest that adverse plantar pressure patterns are associated with redistribution of joint moments, and a consequent reduced capacity to control forward velocity at heel strike.

One-fits-all pretreatment protocol facilitating Fluorescence In Situ Hybridization on formalin-fixed paraffin-embedded, fresh frozen and cytological slides.

BACKGROUND: The Fluorescence In Situ Hybridization (FISH) technique is a very useful tool for diagnostic and prognostic purposes in molecular pathology. However, clinical testing on patient tissue is challenging due to variables of tissue processing that can influence the quality of the results. This emphasizes the necessity of a standardized FISH protocol with a high hybridization efficiency. We present a pretreatment protocol that is easy, reproducible, cost-effective, and facilitates FISH on all types of patient material simultaneously with good quality results.During validation, FISH analysis was performed simultaneously on formalin-fixed paraffin-embedded, fresh frozen and cytological patient material in combination with commercial probes using our optimized one-fits-all pretreatment protocol. An optimally processed sample is characterized by strong specific signals, intact nuclear membranes, non-disturbing autofluorescence and a homogeneous DAPI staining. RESULTS: In our retrospective cohort of 3881 patient samples, overall 93% of the FISH samples displayed good quality results leading to a patient diagnosis. All FISH were assessed on quality aspects such as adequacy and consistency of signal strength (brightness), lack of background and / or cross-hybridization signals, and additionally the presence of appropriate control signals were evaluated to assure probe accuracy. In our analysis 38 different FISH probes from 3 commercial manufacturers were used (Cytocell, Vysis and ZytoLight). The majority of the patients in this cohort displayed good signal quality and barely non-specific background fluorescence on all tissue types independent of which commercial probe was used. CONCLUSION: The optimized one-fits-all FISH method is robust, reliable and reproducible to deliver an accurate result for patient diagnostics in a lean workflow and cost-effective manner. This protocol can be used for widespread application in cancer and non-cancer diagnostics and research.

Relationship between facet joint distraction during anterior cervical discectomy and fusion for trauma and functional outcome.

Aims: The purpose of this retrospective study was to investigate the clinical relevance of increased facet joint distraction as a result of anterior cervical decompression and fusion (ACDF) for trauma. Patients and Methods: A total of 155 patients (130 men, 25 women. Mean age 42.7 years; 16 to 87) who had undergone ACDF between 1 January 2001 and 1 January 2016 were included in the study. Outcome measures included the Neck Disability Index (NDI) and visual analogue scale (VAS) for pain. Lateral cervical spine radiographs taken in the immediate postoperative period were reviewed to compare the interfacet distance of the operated segment with those of the facet joints above and below. Results: There was a statistically significant relationship between greater facet distraction and increased NDI and VAS pain scores. This was further confirmed by Spearman correlation, which showed evidence of a moderate correlation between both NDI score and facet joint distraction (Spearman correlation coefficient 0.34; p < 0.001) and VAS score and facet distraction (Spearman correlation coefficient 0.52; p < 0.001). Furthermore, there was a discernible transition point between outcome scores. Significantly worse outcomes, in terms of both NDI scores (17.8 vs 8.2; p < 0.001) and VAS scores (4.5 vs 1.3; p < 0.001), were seen with facet distraction of 3 mm or more. Patients who went on to have a posterior fusion also had increased NDI and VAS scores, independent of facet distraction. Conclusion: After undergoing ACDF for the treatment of cervical spine injury, patients with facet joint distraction of 3 mm or more have worse NDI and VAS pain scores. Cite this article: Bone Joint J 2018;100-B:1201-7.

Selective vitamin D receptor modulators and their effects on colorectal tumor growth.

The active form of vitamin D, 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], is an endocrine hormone whose classic role is the maintenance of calcium homeostasis. It is well documented that 1,25(OH)(2)D(3) also has anti-tumor effects on a number of cancers and cancer cell lines including breast, colorectal, gastric, liver, ovarian, prostate, and non-melanoma skin cancers. Included in the anti-tumor activities of 1,25(OH)(2)D(3) are its ability to cause antiproliferation, prodifferentation and decrease angiogenesis. Furthermore, through regulation of the plaminogen activator (PA) system and a class of proteolytic enzymes called matrix metalloproteinases (MMPs), 1,25(OH)(2)D(3) reduces the invasive spread of tumor cells. Because of the calcemic limitations of using 1,25(OH)(2)D(3) as a therapy, we have tested the effects of a novel Gemini vitamin D analogue, Deuterated Gemini (DG), on mouse colorectal cancer. We demonstrated that DG is more potent in reducing tumor volume and mass, compared to control and 1,25(OH)(2)D(3). DG significantly prevented (100% reduction, p<0.05) the invasive spread of colorectal tumor cells into the surrounding muscle, and had no effect on serum calcium levels. Thus, DG acts as a selective vitamin D receptor modulator (SVDRM) by enhancing select anti-tumor characteristic 1,25(OH)(2)D(3) activities, without inducing hypercalcemia. Thus, DG shows promise in the development of colorectal cancer therapies.

Amplification and protein overexpression of cyclin D1: Predictor of occult nodal metastasis in early oral cancer.

BACKGROUND: Accurate nodal staging is pivotal for treatment planning in early (stage I-II) oral cancer. Unfortunately, current imaging modalities lack sensitivity to detect occult nodal metastases. Chromosomal region 11q13, including genes CCND1, Fas-associated death domain (FADD), and CTTN, is often amplified in oral cancer with nodal metastases. However, evidence in predicting occult nodal metastases is limited. METHODS: In 158 patients with early tongue and floor of mouth (FOM) squamous cell carcinomas, both CCND1 amplification and cyclin D1, FADD, and cortactin protein expression were correlated with occult nodal metastases. RESULTS: CCND1 amplification and cyclin D1 expression correlated with occult nodal metastases. Cyclin D1 expression was validated in an independent multicenter cohort, confirming the correlation with occult nodal metastases in early FOM cancers. CONCLUSION: Cyclin D1 is a predictive biomarker for occult nodal metastases in early FOM cancers. Prospective research on biopsy material should confirm these results before implementing its use in routine clinical practice. © 2016 Wiley Periodicals, Inc. Head Neck 39: 326-333, 2017.

Interdisciplinary management of an adolescent patient with significant previous trauma to the upper incisors.

Significant dental trauma may result in short-term and long-term clinical dilemmas. There are many factors to consider when formulating the relevant and reasonable treatment options for such patients. Interdisciplinary management has the potential to significantly improve both aesthetic and functional outcomes in challenging cases. With respect to each presented option, the patient must be informed of the inherent advantages and disadvantages, the appropriate treatment timing, duration and the costs involved, both financial and biological.

Partial irradiation of the brain.

Late radiation injury is the main dose-limiting factor for radiotherapy of tumors of the central nervous system (CNS). Clinical experience as well as analyses of complication data, both for brain necrosis and for changes in neuroimaging after radiosurgery, suggest a pronounced volume effect in the brain. However, the relationships of dose and volume to complications after irradiation of lesions in the brain have yet to be quantitatively assessed. The quantification of volume effects and the modeling of normal tissue response to partial organ irradiation of the brain are particularly demanding because of the highly differentiated and complex structure of the brain and the variety of endpoints after radiotherapy for CNS diseases. This article summarizes the existing clinical data that demonstrate a volume effect in the brain and the current state of knowledge regarding the modeling of complications following partial irradiation of the brain.

Genetics in the study of mosquito susceptibility to Plasmodium.

Within the past several years, a number of powerful genetic and genomic tools have been developed for use in research on the African malaria vector Anopheles gambiae. While these tools have been developed with a broad range of potential applications in mind, they have been particularly useful in advancing the effort to clone a set of An. gambiae genes that enable a refractory strain of this mosquito to encapsulate and kill a wide variety of different malaria parasites to which this mosquito is normally fully susceptible. This paper describes the latest progress in this map-based cloning research, which involves the collaborative contributions of a number of different laboratories in Europe and the United States.

Increased forefoot loading is associated with an increased plantar flexion moment.

The aim of this study was to identify the cascade of effects leading from alterations in force generation around the ankle joint to increased plantar pressures under the forefoot. Gait analysis including plantar pressure measurement was performed at an individually preferred and a standardized, imposed gait velocity in diabetic subjects with polyneuropathy (n=94), without polyneuropathy (n=39) and healthy elderly (n=19). The plantar flexion moment at 40% of the stance phase was negatively correlated with the displacement rate of center of pressure (r=-.749, p<.001 at the imposed, and r=-.693, p<.001 at the preferred gait velocity). Displacement rate of center of pressure was strongly correlated with forefoot loading (r=-.837, p<.001 at the imposed, and r=-.731, p<.001 at the preferred gait velocity). People with a relatively high plantar flexion moment at 40% of the stance phase, have a faster forward transfer of center of pressure and consequently higher loading of the forefoot. This indicates that interventions aimed at increasing the control of the roll-off of the foot may contribute to a better plantar pressure distribution.

Calculation of plantar pressure time integral, an alternative approach.

In plantar pressure measurement, both peak pressure and pressure time integral are used as variables to assess plantar loading. However, pressure time integral shows a high concordance with peak pressure. Many researchers and clinicians use Novel software (Novel GmbH Inc., Munich, Germany) that calculates this variable as the summation of the products of peak pressure and duration per time sample, which is not a genuine integral of pressure over time. Therefore, an alternative calculation method was introduced. The aim of this study was to explore the relevance of this alternative method, in different populations. Plantar pressure variables were measured in 76 people with diabetic polyneuropathy, 33 diabetic controls without polyneuropathy and 19 healthy subjects. Peak pressure and pressure time integral were obtained using Novel software. The quotient of the genuine force time integral over contact area was obtained as the alternative pressure time integral calculation. This new alternative method correlated less with peak pressure than the pressure time integral as calculated by Novel. The two methods differed significantly and these differences varied between the foot sole areas and between groups. The largest differences were found under the metatarsal heads in the group with diabetic polyneuropathy. From a theoretical perspective, the alternative approach provides a more valid calculation of the pressure time integral. In addition, this study showed that the alternative calculation is of added value, along peak pressure calculation, to interpret adapted plantar pressures patterns in particular in patients at risk for foot ulceration.