Complications of spinal cord arteriography: prospective assessment of risk for diagnostic procedures

A prospective study was done of complications associated with 134 consecutive diagnostic spinal cord arteriograms in 96 patients (63 men and 33 women aged 17-78 years). Patients were examined for either arteriovenous malformation (n = 88) or tumor (n = 8), as indicated by myelography. Among the complications, 11 (8.2%) were local, five (3.7%) were systemic nonneurologic, and three (2.2%) were neurologic (two were associated with full recovery in less than 24 hours, and one was associated with full recovery in less than 1 week). No specific clinical or technical factors were significantly associated with the development of neurologic complications. Details of the clinical profile, angiographic technique, and pathologic findings for each patient were recorded and analyzed with respect to the potential risk for arteriographic complications. Diagnostic spinal cord arteriography had an acceptable risk within the range of other neuroangiographic diagnostic procedures.     

The motor nerve supply of the external urethral sphincter muscles: An electrophysiologic study

The term “intrinsic external urethral sphincter” has recently been applied to the striated muscle immediately surrounding the membranous urethra, thus distinguishing and separating it from the periurethral striated muscle which is a component of the pelvic floor. The innervation of the intrinsic external urethral sphincter is still controversial. Six male patients with a sustained spinal cord lesion above D-4 underwent electrophysiological evaluation of the reflex and direct evoked responses to stimulation of the pudendal nerve branches in the perineal region. Recording of the motor unit potentials was performed using a catheter-mounted concentric needle introduced into the intrinsic external urethral sphincter transurethrally. The results of this study indicate that the pudendal nerve, i.e., somatic, plays an important role in the innervation of the intrinsic external urethral muscle. It does not, however, exclude the possibility that the autonomic nervous system also innervates this muscle.     

Secondary and tertiary structure modeling reveals effects of novel mutations in polycystic liver disease genes PRKCSH and SEC63

Waanders E, Venselaar H, te Morsche RHM, de Koning DB, Kamath PS, Torres VE, Somlo S, Drenth JPH. Secondary and tertiary structure modeling reveals effects of novel mutations in polycystic liver disease genes PRKCSH and SEC63. Polycystic liver disease (PCLD) is characterized by intralobular bile duct cysts in the liver. It is caused by mutations in PRKCSH, encoding hepatocystin, and SEC63, encoding Sec63p. The main goals of this study were to screen for novel mutations and to analyze mutations for effects on protein structure and function. We screened 464 subjects including 76 probands by direct sequencing or conformation‐sensitive capillary electrophoresis. We analyzed the effects of all known and novel mutations using a combination of splice site recognition, evolutionary conservation, secondary and tertiary structure predictions, Poly Phen , and p Mut and sift . We identified a total of 26 novel mutations in PRKCSH (n = 14) and SEC63 (n = 12), including four splice site mutations, eight insertions/ deletions, six non‐sense mutations, and eight missense mutations. Out of 48 PCLD mutations, 13 were predicted to affect splicing. Most mutations were located in highly conserved regions and homology modeling for two domains of Sec63p showed severe effects of the residue substitutions. In conclusion, we identified 26 novel mutations associated with PCLD and we provide in silico analysis in order to delineate the role of these mutations.     

Standardisation of anal sphincter EMG: high and low threshold motor units.

OBJECTIVE: The anal sphincter muscle has a proportion of low threshold motor units (MUs) that are continuously active and other, recruitable high threshold MUs. In standard EMG recordings, motor unit potentials (MUPs) of the later seem to be of higher amplitudes. A quantitative EMG study was performed to assess possible consequences of sampling MUPs at different levels of sphincter activation. METHODS: Fifteen females without uroneurological disorders were studied. After insertion, standard concentric EMG needle was left in the anal sphincter muscle undisturbed for 1 min; then 30 s of the remaining continuous, and 1 min of voluntarily increased EMG activity were recorded on a DAT recorder. MUPs were collected and analysed by 'Multi-MUP' analysis. MUPs analysed during relaxation constituted the 'low threshold MUP pool'. MUPs sampled on activation were checked for those, already sampled during relaxation, (which were discarded), and the remaining MUPs constituted the 'high threshold MUP pool'. Parameters of both MUP pools were compared. RESULTS: High threshold MUPs were found to be significantly larger than low threshold MUPs. CONCLUSIONS: EMG investigator should be aware of the differences of MUPs sampled at various anal sphincter activity levels. For the technique of 'Multi-MUP' analysis sampling at an activity level which provides 3-5 MUPs per detection site would seem practical, providing a standardised approach suitable for comparing normative data with individual findings from most patients.     

Clinical Outcomes in Stage III Non-small Cell Lung Cancer Patients Treated with Durvalumab After Sequential Or Concurrent Platinum-based Chemoradiotherapy – Single Institute Experience

BackgroundChemoradiotherapy (ChT-RT) followed by 12-month durvalumab is the new standard treatment for unresectable stage III non-small cell lung cancer. Survival data for patients from everyday routine clinical practice is scarce, as well as potential impact on treatment efficacy of sequential or concomitant chemotherapy and the usage of gemcitabine.Patients and methodsWe retrospectively analysed unresectable stage III NSCLC patients who were treated with durvalumab after radical concurrent or sequential chemotherapy (ChT) from December 2017 and completed treatment until December 2020. We assessed progression free survival (PFS), overall survival (OS) and toxicity regarding baseline characteristic of patients.ResultsEighty-five patients with median age of 63 years of which 70.6% were male, 56.5% in stage IIIB and 58.8% with squamous cell carcinoma, were included in the analysis. Thirty-one patients received sequential ChT only, 51 patients received induction and concurrent ChT and 3 patients received concurrent ChT only. Seventy-nine patients (92.9%) received gemcitabine and cisplatin as induction chemotherapy and switched to etoposide and cisplatin during concurrent treatment with radiotherapy (RT). Patients started durvalumab after a median of 57 days (range 12–99 days) from the end of the RT and were treated with the median of 10.8 (range 0.5–12 months) months. Forty-one patients (48.2%) completed treatment with planned 12-month therapy, 25 patients (29.4%) completed treatment early due to the toxicity and 16 patients (18.8%) due to the disease progression. Median PFS was 22.0 months, 12- and estimated 24-month PFS were 71% (95% CI: 61.2–80.8%) and 45.8% (95% CI: 32.7–58.9%). With the median follow-up time of 23 months (range 2–35 months), median OS has not been reached. Twelve- and estimated 24-month OS were 86.7% (95% CI: 79.5–93.9%) and 68.6% (95% CI: 57.2–79.9%).ConclusionsOur survival data are comparable with published research as well as with recently published real-world reports. Additionally, the regimen with gemcitabine and platinum-based chemotherapy as induction treatment was efficient and well tolerated.Key words: non-small cell lung cancer, stage III, chemoradiotherapy, durvalumab     

Germline mutation in BRAF codon 600 is compatible with human development: de novo p.V600G mutation identified in a patient with CFC syndrome

Champion KJ, Bunag C, Estep AL, Jones JR, Bolt CH, Rogers RC, Rauen KA, Everman DB. Germline mutation in BRAF codon 600 is compatible with human development: de novo p.V600G mutation identified in a patient with CFC syndrome. BRAF, the protein product of BRAF, is a serine/threonine protein kinase and one of the direct downstream effectors of Ras. Somatic mutations in BRAF occur in numerous human cancers, whereas germline BRAF mutations cause cardio‐facio‐cutaneous (CFC) syndrome. One recurrent somatic mutation, p.V600E, is frequently found in several tumor types, such as melanoma, papillary thyroid carcinoma, colon cancer, and ovarian cancer. However, a germline mutation affecting codon 600 has never been described. Here, we present a patient with CFC syndrome and a de novo germline mutation involving codon 600 of BRAF, thus providing the first evidence that a pathogenic germline mutation involving this critical codon is not only compatible with development but can also cause the CFC phenotype. In vitro functional analysis shows that this mutation, which replaces a valine with a glycine at codon 600 (p.V600G), leads to increased ERK and ELK phosphorylation compared to wild‐type BRAF but is less strongly activating than the cancer‐associated p.V600E mutation.