Erratum: Voluntary wheel running complements microdystrophin gene therapy to improve muscle function in mdx mice.

[This corrects the article DOI: 10.1016/j.omtm.2021.02.024.].

Voluntary wheel running complements microdystrophin gene therapy to improve muscle function in mdx mice.

We tested the hypothesis that voluntary wheel running would complement microdystrophin gene therapy to improve muscle function in young mdx mice, a model of Duchenne muscular dystrophy. mdx mice injected with a single dose of AAV9-CK8-microdystrophin or vehicle at age 7 weeks were assigned to three groups: mdxRGT (run, gene therapy), mdxGT (no run, gene therapy), or mdx (no run, no gene therapy). Wild-type (WT) mice were assigned to WTR (run) and WT (no run) groups. WTR and mdxRGT performed voluntary wheel running for 21 weeks; remaining groups were cage active. Robust expression of microdystrophin occurred in heart and limb muscles of treated mice. mdxRGT versus mdxGT mice showed increased microdystrophin in quadriceps but decreased levels in diaphragm. mdx final treadmill fatigue time was depressed compared to all groups, improved in mdxGT, and highest in mdxRGT. Both weekly running distance (km) and final treadmill fatigue time for mdxRGT and WTR were similar. Remarkably, mdxRGT diaphragm power was only rescued to 60% of WT, suggesting a negative impact of running. However, potential changes in fiber type distribution in mdxRGT diaphragms could indicate an adaptation to trade power for endurance. Post-treatment in vivo maximal plantar flexor torque relative to baseline values was greater for mdxGT and mdxRGT versus all other groups. Mitochondrial respiration rates from red quadriceps fibers were significantly improved in mdxGT animals, but the greatest bioenergetic benefit was observed in the mdxRGT group. Additional assessments revealed partial to full functional restoration in mdxGT and mdxRGT muscles relative to WT. These data demonstrate that voluntary wheel running combined with microdystrophin gene therapy in young mdx mice improved whole-body performance, affected muscle function differentially, mitigated energetic deficits, but also revealed some detrimental effects of exercise. With microdystrophin gene therapy currently in clinical trials, these data may help us understand the potential impact of exercise in treated patients.

Cardiac tamponade following penetrating mediastinal injuries: improved survival with early pericardiocentesis.

UNLABELLED: Cardiac tamponade was diagnosed in 197 patients admitted over 20 years (1955-1974) to the Charity Hospital of New Orleans, for emergency treatment of pentrating mediastinal injuries. Of the 197, 174 definitively treated patients followed one of three patterns of management: 96 had OR thoracotomy, 68% were unstable, and preoperative pericardiocentesis reduced mortality from 25 to 11% (p less than 0.01); 44 had emergency thoracotomy, 91% were unstable, and prethoractomy pericardiocentesis decreased mortality from 94 to 63% (p less than 0.05); 34 patients primarily with isolated stab wounds, were treated nonsurgically with pericardiocentesis and observation, only 50% were unstable and there was 15% mortality. Recurrent tamponade did not significantly increase overall or operative mortality in patients with pericardiocentesis. RECOMMENDATIONS: early, even presumptive, diagnosis of tamponade; immediate pericardial decompression via pericardiocentesis; and rapid transfer to OR for thoracotomy or sternotomy and cardiorrhaphy with continous pericardial decompression via intrapericardial catheter.

Surgical treatment of advanced carcinomas of the base of the tongue.

During the decade of 1964 through 1973, thirty-four patients with advanced squamous carcinoma of the base of the tongue (20 with T3 lesions and 14 with T4 lesions) were treated by surgical resection. These patients underwent an operative procedure as the only and definitive form of treatment. Twenty-eight (82.3 per cent) presented with clinically positive cervical nodal metastases (4 staged N1, 13 staged N2, and 11 staged N3). The number of primary lesions controlled, cervical metastasis, and the failures of treatment were analyzed. The patients were followed for a minimum of two years or until death or recurrence. The determinate control at two years was 27 per cent and the final determinate survival 20 per cent. Fifteen patients (44.2 per cent) required laryngectomy as part of the primary surgical treatment. The surgical procedures used and other therapeutic options available are discussed.

Adenocarcinoma of the stomach: review of 1,497 cases.

The records of 1,497 patients with histologically proven adenocarcinoma of the stomach were reviewed from Charity Hospital over the 25-year period, 1948 to 1973. The operability rate was 82% and the resectability rate was 48%. In this series gastric carcinoma predominated in males and Negroes. Necropsy studies indicate a similar frequency of involvement of various organs in patients not operated upon as well as those subjected to a prior operation, which suggests the need for some therapeutic endeavors aimed at a wider base than the primary organ. The five-year survival rate, 7.4 overall, varied from 2.0% after esophagogastrectomy to 22.1% after radical subtotal gastrectomy, and to 30.3% for those with localized disease. One hundred one patients survived five years or more, and 5.4% survived ten years or more after the diagnosis of gastric cancer. Radical subtotal gastrectomy gave the best results in this series, whether measured in terms of median survival, five-year survival, or operative mortality. Esophagogastrectomy and by-pass procedures had high mortality and low survival rates, and should be reserved for special conditions.