Heterozygous POLG variant Ser1181Asn co-segregating in a family with autosomal dominant axonal neuropathy, proximal muscle fatigability, ptosis, and ragged red fibers.

By whole-exome sequencing, we found the heterozygous POLG variant c.3542G>A; p.Ser1181Asn in a family of four affected individuals, presenting with a mixed neuro-myopathic phenotype. The variant is located within the active site of polymerase gamma, in a cluster region associated with an autosomal dominant inheritance. In adolescence, the index developed distal atrophies and weakness, sensory loss, afferent ataxia, double vision, and bilateral ptosis. One older sister presented with Charcot-Marie-Tooth-like symptoms, while the youngest sister and father reported exercise-induced muscle pain and proximal weakness. In none of the individuals, we observed any involvement of the central nervous system. Muscle biopsies obtained from the father and the older sister showed ragged-red fibers, and electron microscopy confirmed mitochondrial damage. We conclude that this novel POLG variant explains this family's phenotype.

Immunoglobulins to mitigate paraneoplastic Lambert Eaton Myasthenic Syndrome under checkpoint inhibition in Merkel cell carcinoma.

Lambert-Eaton myasthenic syndrome (LEMS) is a rare, autoimmune or paraneoplastic condition characterized by muscle weakness and fatigability. In cancer therapy, immune checkpoint inhibitors (ICI) sensitize the immune system for tumor antigens. We report a 62-year-old, female patient with paraneoplastic LEMS as first manifestation of Merkel cell carcinoma. Under avelumab, the LEMS exacerbated with worsening of limb weakness and a severely reduced vital capacity (< 1 l). To treat this immunological side effect, we added a regimen with intravenous immunoglobulins. Hereby, the LEMS improved significantly. As we were able to continue the cancer treatment, the Merkel cell carcinoma has been in remission so far. This is the first description of paraneoplastic LEMS, avelumab, and Merkel cell carcinoma. We conclude that immunoglobulins are an option to control an ICI-associated deterioration of paraneoplastic symptoms.

Predictors of long-term survival in patients with colorectal liver metastases: a single center study and review of the literature.

PURPOSE: Prognosis after resection of liver metastases of colorectal cancer is influenced by a variety of clinical factors. For more than 20 years, efforts have been made to restructure and simplify prognostic parameters into clinical scores. We evaluated the influence of various clinical and pathological factors on survival and recurrence and developed a simple model for risk stratification. METHODS: We have analyzed a total of 13 prognostic factors in 382 consecutive and prospectively enrolled R0-resected patients and applied our data set to ten published prognostic scoring systems. Prognostic factors that influenced disease-specific and disease-free survival were included into a model clinical risk score. RESULTS: The 5- and 10-year observed survival rates were 43% and 28%, respectively, for all 382 patients. The disease-specific 5- and 10-year survival rates were 49% and 37%, respectively; the 5- and 10-year recurrence rates were 68% and 70%, respectively. For patients with synchronous liver metastases, survival was not affected by the timing of liver resection. The prognosis after treatment of any recurrence was best after the accomplishment of a repeated R0 situation, independent of the location of the recurrence. In the multivariate analysis, the disease-specific survival and recurrence rates were statistically significantly influenced by more than three lymph node metastases of the primary tumor, more than two lesions within the liver, and the presence of extrahepatic tumor. CONCLUSIONS: From these data, we have developed a simple score for the risk stratification which may be useful for future studies on interdisciplinary management of colorectal liver metastases.

Every slow-wave impulse is associated with motor activity of the human stomach.

Using a newly developed high-resolution three-dimensional magnetic detector system (3D-MAGMA), we observed periodical movements of a small magnetic marker in the human stomach at the typical gastric slow-wave frequency, that is 3 min(-1). Thus we hypothesized that each gastric slow wave induces a motor response that is not strong enough to be detected by conventional methods. Electrogastrographies (EGG, Medtronic, Minneapolis, MN) for measurement of gastric slow waves and 3D-MAGMA (Innovent, Jena, Germany) measurements were simultaneously performed in 21 healthy volunteers (10 men, 40.4+/-13.6 yr; 11 women, 35.8+/-11.6 yr). The 3D-MAGMA system contains 27 highly sensitive magnetic field sensors that are able to locate a magnetic pill inside a human body with an accuracy of +/-5 mm or less in position and +/-2 degrees in orientation at a frequency of 50 Hz. Gastric transit time of the magnetic marker ranged from 19 to 154 min. The mean dominant EGG frequency while the marker was in the stomach was 2.87+/-0.15 cpm. The mean dominant 3D-MAGMA frequency during this interval was nearly identical; that is, 2.85+/-0.15 movements per minute. We observed a strong linear correlation between individual dominant EGG and 3D-MAGMA frequency (R=0.66, P=0.0011). Our findings suggest that each gastric slow wave induces a minute contraction that is too small to be detected by conventional motility investigations but can be recorded by the 3D-MAGMA system. The present slow-wave theory that assumes that the slow wave is a pure electrical signal should be reconsidered.