VIM thalamic stimulation for tremor in a patient with IgM paraproteinaemic demyelinating neuropathy.

We demonstrate the effect of deep brain stimulation of the ventral intermediate thalamic nucleus on intractable action tremor, in a 72-year-old man suffering from neuropathy associated with monoclonal gammopathy.     

Genomewide profiling of copy‐number alteration in monoclonal gammopathy of undetermined significance

Monoclonal gammopathy of undetermined significance (MGUS) is a benign condition with an approximate 1% annual risk of symptomatic plasma cell disorder development, mostly to multiple myeloma (MM). We performed genomewide screening of copy‐number alterations (CNAs) in 90 MGUS and 33 MM patients using high‐density DNA microarrays. We identified CNAs in a smaller proportion of MGUS (65.6%) than in MM (100.0%, P = 1.31 × 10^?5) and showed median number of CNAs is lower in MGUS (3, range 0–22) than in MM (13, range 4–38, P = 1.82 × 10^?10). In the MGUS cohort, the most frequent losses were located at 1p (5.6%), 6q (6.7%), 13q (30.0%), 14q (14.4%), 16q (8.9%), 21q (5.6%), and gains at 1q (23.3%), 2p (6.7%), 6p (13.3%), and Xq (7.8%). Hyperdiploidy was detected in 38.9% of MGUS cases, and the most frequent whole chromosome gains were 3 (25.6%), 5 (23.3%), 9 (37.8%), 15 (23.3%), and 19 (32.2%). We also identified CNAs such as 1p, 6q, 8p, 12p, 13q, 16q losses, 1q gain and hypodiploidy, which are potentially associated with an adverse prognosis in MGUS. In summary, we showed that MGUS is similar to MM in that it is a genetically heterogeneous disorder, but overall cytogenetic instability is lower than in MM, which confirms that genetic abnormalities play important role in monoclonal gammopathies.     

Ipilimumab for the treatment of metastatic prostate cancer

Introduction: Immunotherapy with checkpoint inhibitors is beginning to be recognized as a valid weapon for the treatment of metastatic prostate cancer (PCa) when chemotherapy fails. Ipilimumab (ipi) is a fully humanized monoclonal antibody that blocks the activity of CTLA4. It also has a molecular weight of 148 kDa and is water-soluble at physiological pH. Ipi was first approved by the FDA for the treatment of malignant melanoma and is currently being studied in metastatic castration-resistant prostate cancer, with promising early results.

Areas covered: The aim of this review is to collate the most significant preclinical and clinical studies available that look at ipi to propose new strategies for the future.

Expert opinion: Additional studies are required to reduce toxicity and increase the activity of ipi in PCa. A possible strategy is to combine ipi with standard anti-cancer therapeutics such as vaccines, PDL1 inhibitors, antiandrogen drugs, and chemotherapy agents. Several initial results have suggested that combination strategies are useful to increase the activity in mCRPC, even if the toxicity of the treatment can increase. The activity of combined treatments is still not predictable, but considering the ongoing studies, we believe that they have good potential that will lead to the discovery of an optimal therapeutic strategy.     

Osteoinductive 3D scaffolds prepared by blend centrifugal spinning for long-term delivery of osteogenic supplements

Bone regeneration is a long-term process requiring proper scaffolding and drug delivery systems. The current study delivers a three-dimensional (3D) scaffold prepared by blend centrifugal spinning loaded with the osteogenic supplements (OS) β-glycerol phosphate, ascorbate-2-phosphate and dexamethasone. The OS were successfully encapsulated into a fibrous scaffold and showed sustained release for 30 days. Furthermore, biological testing showed the osteoinductive properties of the scaffolds on a model of human mesenchymal stem cells and stimulatory effect on a model of osteoblasts. The osteoinductive properties were further proved in vivo in critical size defects of rabbits. The amount of bone trabecules was bigger compared to control fibers without OS. The results indicate that due to its long-term drug releasing properties, single step fabrication process and 3D structure, the system shows ideal properties for use as a cell-free bone implant in tissue-engineering.

Bone regeneration is a long-term process requiring proper scaffolding and drug delivery systems.     

Elipse™, a Procedureless Gastric Balloon for Weight Loss: a Proof-of-Concept Pilot Study

Background

Endoscopic gastric balloons have been used effectively as weight loss devices for decades, but the requirement for endoscopy and sedation poses several limitations. The goal of this pilot study was to evaluate the safety and performance of a prototype version of Elipse?, a procedureless gastric balloon.

Methods

Eight patients (mean BMI?=?31.0 kg/m²) participated in this study. Each patient swallowed one Elipse? balloon intended to remain in the stomach for 6 weeks, self-empty, and then pass. Each balloon was filled with 450 mL of filling fluid. Patients returned every 2 weeks for abdominal ultrasound. No specific diet or exercise plan was prescribed.

Results

All eight patients successfully swallowed the device. The most common adverse events were nausea and vomiting. There were no serious adverse events, and all balloons were excreted safely. Despite not being prescribed a diet or exercise plan, all eight patients lost weight. In 6/8 patients, the balloon remained full through 6 weeks, self-emptied, and passed. In one patient, the balloon appeared partially collapsed on ultrasound after 11 days and was endoscopically punctured. One asymptomatic patient elected to have the balloon endoscopically punctured after 19 days. Both balloons passed in the stool after 4 days. In both cases, endoscopic examination of the upper GI tract showed no abnormalities.

Conclusions

This pilot study demonstrates the safety and performance of Elipse?, a procedureless gastric balloon for weight loss. Future studies will test a commercial design filled to 550 mL intended to last in the stomach for at least 12 weeks.

     

Rare presentation of non-Hodgkin lymphoma of the thoracolumbar spine in pregnancy with 7 years' survival

A rare, so far unpublished, case of non-Hodgkin lymphoma in 26-year-old pregnant woman is presented. As X ray examination and other investigations were avoided during her pregnancy, the discrete signs of spinal cord compression led to sudden severe neurological deterioration after delivery. This necessitated emergency decompression and stabilization of the spine. Acute surgical treatment resulted in complete functional recovery. It was followed by chemotherapy and radiotherapy, which led to disease-free survival 7 years after the surgery. Magnetic resonance imaging is the examination of choice when long-lasting back pain during pregnancy does not resolve with bed rest.     

External Cephalic Version at Term

Summary: The case notes of women with singleton term (37 weeks' gestation and beyond) breech presentation and delivery were retrospectively reviewed. Thirty-two of the 72 women in the study group had attempted external cephalic version at term, with a success rate of 53% (17 women). The Caesarean section rate was significantly lower in the group which had attempted ECV compared to the group which did not.     

Recombinant protein and DNA vaccines derived from hsp60 Trichophyton mentagrophytes control the clinical course of trichophytosis in bovine species and guinea-pigs

Heat shock proteins (hsp) were identified in many infectious agents as immunodominant antigens with a protective effect. Immunization of laboratory animals by selected representants of hsp60, hsp70 and hsp90 isolated from several pathogens induced protective host immunity and significantly reduced clinical manifestation of infection. The present study involves preparation of a recombinant protein vaccine and a DNA vaccine. Both vaccines were derived from the hsp60 of the dermatophyte, Trichophyton mentagrophytes. Challenge trials with evaluation of the protective effect of vaccination were performed on calves and guinea-pigs. Both vaccination procedures reduced, in statistically significant fashion, the clinical course of skin mycosis in calves experimentally inoculated with the dermatophyte, T. mentagrophytes. In experiments with guinea-pigs, increased protection was only seen with DNA vaccination. After DNA vaccine application, no paravaccination side-effects (granulomas at the injection site, changed total state of the animal) were observed. Only vaccination with the recombinant protein in calf's experiment induced specific serum antibodies. This observation indicates that antibodies are not associated with protection. In summary, DNA vaccine hsp60 is the most promising for prevention of bovine trichophytosis.     

GBV-C/HGV, a new virus as one possible cause of hepatitis of unknown etiology

For etiologically obscure (some 4%) viral hepatitis agents are sought and tested to make elucidation of their cause possible. One of the candidates is since 1995 the newly discovered virus GBV-C/HGV. Despite intense research its relationship to viral hepatitis of obscure origin (VHN) has not been elucidated so far. In the submitted paper the authors attempted to contribute to the elucidation of etiological associations of GBV-C/HGV infection and VHN by comparing the dynamics of markers of the infection in a group of 59 patients with VHN, two control groups exposed to a high risk of parenteral operations and a third comparative group. The first control group comprised 64 patients in a long-term haemodialyzation programme (HD), the second group was formed by 82 patients with haematooncological disease (BD). The third comparative group comprised 22 patients coinfected (CI) with virus of hepatitis C (VHC), or possibly hepatitis B (VHB). The patients with VHN were HBsAg, anti HCV and anti HEV negative. In the majority in the first blood sample transaminases were elevated which was one of the main reasons for examination of GBV-C/HGV RNA. Prevalence of GBV-C/HGV infection, proved by the presence of at least one of the two markers of current or past infection (GBV-C/HGV RNA, antiGBV-C/HGV) was in the compared VHN, HD and BD groups as follows: 88.1%, 59.4% and 43.9%. The frequency of GBV-C/HGV positivity was highest in VHN-76.3%. In control groups HD and BD GBV-C/HGV RNA positivity was substantially lower, 18.8% and 25.6% resp. Long-term continuous viraemia was recorded in patients with VHN in 18.6%. In groups HD and BD it was half that value: 9.3% and 9.18%. In patients with VHN surprisingly after 6.5 months a marked rise of negative findings occurred (5.6x) without the expected increase of antibodies. A similar finding was recorded also in the other groups (HD and BD), incl. CI patients. Disappearance of viraemia was observed most frequently in VHN (55.9%). In groups HD and BD GBV-C/HGV RNA disappeared only in 7.8% and 12.1% resp. In treated patients of the CI group viral RNA was present in 45.5% and it disappeared in 36.4%. On the other hand, seroconversion to antibodies was comparable in VHN, HD and BD (11.9%, 9.4%, 8.5%), only in group CI it was higher (18.2%), obviously in conjunction with treatment of concurrent HCV or HBV infection. Disappearance of viraemia without subsequent seroconversion occurs in GBV-C/HGV infection frequently, the highest rate was observed by the authors in patients with VHN. Disappearance of viraemia does not necessarily imply clearance of GBV-C/HGV but may be due to a change of GBV-C(HGV into a state of persistence without positive laboratory markers of the infection. Persistence of the virus could also be the reason of the assumed conditioned pathogenicity of the virus, and the effect of frequent disappearance of both markers could explain some controversial epidemiological observations when in studies only static data without dynamic associations were used.     

Endometriomas in Pregnancy

Summary: Endometriomas are rare in pregnancy, may not be large, may be difficult to diagnose definitively and although benign, may cause significant complications at any stage during gestation. They remain a management dilemma.