Limited dorsal myeloschisis without extradural stalk continuity to coexisting congenital dermal sinus.

Limited dorsal myeloschisis (LDM) is characterized by a fibroneural tethering stalk linking the skin lesion to the underlying spinal cord. LDM without an extradural stalk is rare. A full-term boy was noted at birth to have a dimple in the upper back (dorsal skin of the lower thoracic region). Computed tomographic scan showed spina bifida at the T9-12 vertebral level and osteochondral tissue at the T10 level. Magnetic resonance imaging (MRI) demonstrated a tiny dorsal lipoma at the T8 vertebral level, but the intradural tethering tract was not apparent. At 18 days of age, the congenital dermal sinus (CDS) tract started from the dimple and terminated at the osteochondral tissue, without continuity of the dura mater, and the osteochondral tissues were resected. At age 2 years 8 months, he developed spastic paresis of the right foot. On MRI, the tethering tract from the dorsal lipoma became apparent. During the second surgery at age 2 years 11 months, the intradural stalk started from the dorsal lipoma and joined the inner surface of the dura mater was untethering from the cord. Postoperatively, right spastic paresis was improved. Histological examination of the intradural stalk revealed the distribution of S100-immunopositive peripheral nerve fibers, which is one of the histopathological hallmarks of LDM. We speculated that the extradural stalk with coexisting CDS originally linked from the skin lesion subsequently regressed and was replaced by fibroadipose tissue with osteochondral tissue migration. Intradural exploration should always be seriously considered in these disorders of persisting neurocutaneous connection.

A single allele of the hsa-miR-302/367 cluster maintains human pluripotent stem cells.

Introduction: In a diploid organism, two alleles from a single genetic locus are expressed to generate a normal phenotype. Heterozygous deleterious mutation causes a reduction of functional proteins to a half dose and insufficient amounts of functional proteins can occur to generate an in-normal phenotype, namely haploinsufficiency. Heterozygous deleterious mutation of microRNAs (miRs), non-coding RNAs that regulate the expression level of target transcripts, is still not well understood. The hsa-miR-302/367 cluster is the most abundant and specifically up-regulated miR cluster in human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) and plays an important role in the maintenance of pluripotency. Methods: We targeted the hsa-miR-302/367 region via a Cas9 nuclease complex with guide RNA and replaced that region with green fluorescent protein (GFP). Using a homologous donor, consisting of left and right arms and GFP, we confirmed deletion of the hsa-miR-302/367 cluster by homologous recombination without cellular destruction by microscopy. We sub-cloned GFP-positive colonies and checked the genotype of each sub-clone by genomic PCR. We then analyzed the pluripotency of heterozygous knockout cells with a hsa-miR-302/367 cluster by assessing cell proliferation ratio, morphology, and undifferentiated marker gene expression. We also used an embryoid body formation assay and transplanted wild-type and heterozygous knockout cells into immune-deficient mice. Furthermore, to analyze the lineage-specific differentiation potential of heterozygous knockout cells, we differentiated both wild-type and heterozygous knockout cells into neural stem cells. Results: Here, we show that the half dose of mature miRs from the hsa-miR-302/367 cluster loci was sufficient for the continued self-renewal of hiPSCs. All GFP-positive clones were revealed to be heterozygous knockout cells, suggesting hsa-miR-302/367 cluster homozygous knockout cells were not maintained. The cell proliferation ratio, morphology, and expression of undifferentiated marker genes were comparable between wild-type and heterozygous knockout of undifferentiated human iPSCs. In addition, we found that heterozygous knockout human iPSCs have the capacity to differentiate into three germ layers, including neural stem cells. Conclusions: Taken together, a single allele of the hsa-miR-302/367 cluster expresses a sufficient amount of miRs to maintain the pluripotent properties of human stem cells.

Synthesis of N-methylated unsymmetric porphyrinoids with restricted N-centered chirality from chlorophyll-a.

Regioselectively N-methylated chlorophyll-a derivatives were prepared as their cationic and hydrophilic species. Both their epimerically pure samples at the chiral methylated nitrogen atom were obtained, and the stereochemistry was proposed by circular dichroism spectral analysis. This is the first example for restricted N-centered chirality in an unsymmetric chlorin core.

Oesophagobronchial perforations after placement of an oesophageal self-expanding metallic stent.

An oesophageal fully covered self-expanding metallic stent (SEMS) was placed in a 54-year-old Japanese man to relieve dysphagia owing to a stage cT1bN3M1c lung adenocarcinoma. High expression of programmed cell death-ligand 1 was microscopically confirmed, and pembrolizumab was subsequently administered. Several days later, the patient was hospitalized with septic shock, and severe mediastinitis and pneumonia caused by oesophageal SEMS-induced oesophageal and bronchial perforations were observed. Thoracoscopic surgery was performed to drain the mediastinal abscess, and an additional oesophageal SEMS was placed to close the oesophageal perforation. The patient gradually recovered from the potentially fatal infection, and the SEMS was retrieved after confirming perforation closure. We re-initiated pembrolizumab administration, and the patient responded well. The present report reveals the potential risk and effectiveness of SEMS, especially when administered with immune checkpoint inhibitors.

Increase in Carbohydrate Antigen 19-9 Levels without Tumor Progression after Polaprezinc Administration that Induced Deep Vein Thrombosis in a Colon Cancer Patient.

Carbohydrate antigen 19-9 (CA 19-9) is a well-known tumor marker of adenocarcinoma (reference range, 37 U/mL). It can also be used, together with computed tomography, to monitor responses and resistance to chemotherapy in cancer patients. False elevation of CA 19-9 levels is often seen in conditions such as biliary tract obstruction and cholangitis. However, whether medication might induce false elevation of CA 19-9 levels has not yet been reported. A 74-year-old man was treated with third-line CPT-11 (irinotecan) plus panitumumab for stage IV cancer of the ascending colon. The patient developed chemotherapy-induced dysgeusia and was treated with polaprezinc. After polaprezinc administration, his CA 19-9 levels gradually increased from 18.9 to 1,699.4 U/mL. He developed deep vein thrombosis (DVT), although it was not associated with progressive disease or metastasis. Upon discontinuation of polaprezinc, CA 19-9 levels gradually decreased. This case demonstrates that polaprezinc may not only induce false elevation of CA 19-9 levels but also cause development of DVT induced by increased CA 19-9 levels, both of which are very rare events.

Antihypertensive drug reduction for treated hypertensive patients during the summer.

Seasonal winter-summer variation in blood pressure (BP) has been reported, but there are few reports on the reduction of antihypertensive medication during the summer. We aimed to investigate the prevalence and details of drug reduction during the summer among outpatients. Among 667 patients, 90 patients (13.5%) had their medication reduced during the summer. The highest rate of drug reduction was for diuretics (17.5%). The patients whose medications were reduced (Group R) took a larger number of drugs and more frequently took diuretics compared with the subjects whose medications were unchanged (N = 559; with no reduction or increase in drugs, Group UC). Moreover, both the office BP and morning home BP of the patients in Group R were significantly lower compared with those of the patients in Group UC. These results suggest that doctors tend to reduce antihypertensive drugs to avoid an excessive decrease in BP especially in patients receiving combination therapy including diuretics.