Successful treatment of childhood intramedullary spinal cord astrocytomas with irinotecan and cisplatin

Childhood spinal cord astrocytomas are rare diseases, and their management is controversial. We report here our successful experience using irinotecan and cisplatin in three consecutive infants with progressing intramedullary astrocytomas. The first patient was a 16-month-old girl who presented with a grade III intramedullary astrocytoma that rapidly progressed after surgery and adjuvant chemotherapy. Weekly irinotecan (50 mg/m(2)) and cisplatin (30 mg/m(2)) for four consecutive weeks (one cycle) for a total of four cycles (I/C regimen) was used in order to avoid or delay radiotherapy. Radiological complete remission was achieved 10 months after completion of therapy, and 3.5 years after diagnosis the patient remains disease free. The second patient was a 19-month-old boy with a C3-T4 grade II intramedullary astrocytoma who received up-front vincristine and carboplatin for two months but remained clinically symptomatic. A followup MRI showed a larger tumor, and the patient was switched to the I/C regimen. A marked clinical improvement occurred after the first cycle, and MRI showed a very good partial remission at the end of therapy. At 16 months after diagnosis, the patient remains disease free. The third patient was a 10-month-old girl with a C2-T3 grade II intramedullary astrocytoma. She presented with severe pain that became steroid dependent during the month she was treated with the vincristine-carboplatin regimen. When she was switched to the I/C regimen, the clinical symptoms responded within days. MRI at the end of therapy showed a significant reduction in tumor size, and one year after diagnosis the patient remains symptom free. Using this I/C regimen for childhood intramedullary astrocytoma, we obtained remarkable clinicoradiological responses while avoiding the use of radiotherapy.     

Resveratrol Improves Motoneuron Function and Extends Survival in SOD1G93A ALS Mice

Amyotrophic lateral sclerosis (ALS) is an adult onset neurodegenerative disease that causes progressive paralysis and death due to degeneration of motoneurons in spinal cord, brainstem and motor cortex. Nowadays, there is no effective therapy and patients die 2–5 years after diagnosis. Resveratrol (trans-3,4′,5-trihydroxystilbene) is a natural polyphenol found in grapes, with promising neuroprotective effects since it induces expression and activation of several neuroprotective pathways involving Sirtuin1 and AMPK. The objective of this work was to assess the effect of resveratrol administration on SOD1^G93A ALS mice. We determined the onset of symptoms by rotarod test and evaluated upper and lower motoneuron function using electrophysiological tests. We assessed the survival of the animals and determined the number of spinal motoneurons. Finally, we further investigated resveratrol mechanism of action by means of western blot and immunohistochemical analysis. Resveratrol treatment from 8 weeks of age significantly delayed disease onset and preserved lower and upper motoneuron function in female and male animals. Moreover, resveratrol significantly extended SOD1^G93A mice lifespan and promoted survival of spinal motoneurons. Delayed resveratrol administration from 12 weeks of age also improved spinal motoneuron function preservation and survival. Further experiments revealed that resveratrol protective effects were associated with increased expression and activation of Sirtuin 1 and AMPK in the ventral spinal cord. Both mediators promoted normalization of the autophagic flux and, more importantly, increased mitochondrial biogenesis in the SOD1^G93A spinal cord. Taken together, our findings suggest that resveratrol may represent a promising therapy for ALS.     

Mapping the brain pathways of declarative verbal memory: Evidence from white matter lesions in the living human brain

Understanding the contribution of the brain white matter pathways to declarative verbal memory processes has been hindered by the lack of an adequate model in humans. An attractive and underexplored approach to study white matter region functionality in the living human brain is through the use of non-aprioristic models which specifically search disrupted white matter pathways. For this purpose, we employed voxel-based lesion–function mapping to correlate white matter lesions on the magnetic resonance images of 46 multiple sclerosis patients with their performance on declarative verbal memory storage and retrieval. White matter correlating with storage was in the temporal lobe–particularly lateral to the hippocampus and in the anterior temporal stem–, in the thalamic region and in the anterior limb of the internal capsule, all on the left hemisphere, and also in the right anterior temporal stem. The same volumes were relevant for retrieval, but to them were added temporo-parieto-frontal paramedian bundles, particularly the cingulum and the fronto-occipital fasciculus. These 3D maps indicate the white matter regions most critically involved in declarative verbal memory in humans.     

Predictors and management of post-banding ulcer bleeding in cirrhosis: A systematic review and meta-analysis

Background and Aims

Post-banding ulcer bleeding (PBUB) is an understudied complication of oesophageal varices endoscopic band ligation (EBL). This systematic review with meta-analysis aimed at: (a) evaluating the incidence of PBUB in patients with cirrhosis treated with EBL in primary or secondary prophylaxis or urgent treatment for acute variceal bleeding and (b) identifying predictors of PBUB.

Methods

We conducted a systematic review of articles in English published in 2006–2022 using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Searches were made in eight databases including Embase, PubMed and Cochrane Library. Random-effects meta-analysis was used to determine the incidence, mean interval and predictors of PBUB.

Results

Eighteen studies (9034 patients) were included. The incidence of PBUB was 5.5% (95% CI 4.3–7.1). The mean time for it to occur was 11 days (95% CI 9.94–11.97). Model for End-stage Liver Disease (MELD) score (OR 1.162, 95% CI 1.047–1.291) and EBL done in emergency setting (OR 4.902, 95% CI 2.99–8.05) independently predicted post-ligation ulcer bleeding. Treatment included drugs, endoscopic procedures and transjugular intrahepatic portosystemic shunt. Refractory bleeding was treated with self-expandable metallic stents or balloon tamponade. Mortality was on average 22.3% (95% CI 14.1–33.6).

Conclusions

Patients with high MELD score and receiving EBL in an emergency setting are more prone to develop PBUB. Prognosis is still poor and the best therapeutic strategy to address remains to be ascertained.     

Late-Onset Inflammatory Adverse Reactions Related to Soft Tissue Filler Injections

An ever-increasing number of persons seek medical solutions to improve the appearance of their aging skin or for aesthetic and cosmetic indications in diverse pathological conditions, such as malformations, trauma, cancer, and orthopedic, urological, or ophthalmological conditions. Currently, physicians have many different types of dermal and subdermal fillers, such as non-permanent, permanent, reversible, or non-reversible materials. Despite the claims of manufacturers and different authors that fillers are non-toxic and non-immunogenic or that complications are very uncommon, unwanted side effects do occur with all compounds used. Implanted, injected, and blood-contact biomaterials trigger a wide variety of adverse reactions, including inflammation, thrombosis, and excessive fibrosis. Usually, these adverse reactions are associated with the accumulation of large numbers of mononuclear cells. The adverse reactions related to fillers comprise a broad range of manifestations, which may appear early or late and range from local to systemic. Clinicians should be aware of them since the patient often denies the antecedent of injection or is unaware of the material employed. Most of these adverse effects seem to have an immunological basis, the fillers acting more as adjuvants than as direct T-cell activators, on a background of genetic predisposition. Their treatment has not been the subject of well-designed studies; management of both acute and systemic reactions is often difficult, and requires anti-inflammatory and occasionally immunosuppressive therapy. The clinical, pathological, and therapeutic aspects of inflammatory and immune-mediated late-onset adverse reactions related to soft tissue filler injections are thoroughly reviewed herein.