Dalbavancin During the COVID-19 Pandemic.

The COVID-19 pandemic, which started in March of 2020, and its associated surges have had an immense impact on the ability of medical staff to perform their daily activities. Thus, we sought to direct patients who had gram-positive Acute Bacterial Skin and Skin Structure Infections (ABSSSI) to our Outpatient Department/Wound Care Center for treatment. We met the challenge of the pandemic by shifting care in the treatment of ABSSSI using a new antibiotic delivery system. We examined the use and cost-effectiveness of Dalbavancin, a unique long-acting lipoglycopeptide antibiotic that is used in the treatment of acute bacterial skin and skin structure infections, during the COVID-19 pandemic. A total of 631 patients were treated in the Outpatient Department/Wound Care Center, with re-evaluation at the Wound Care Center on Day 3 post-infusion. The primary test of cure or major improvement was based on a 4- to 6-week re-assessment by the Wound Care Center Faculty (i.e., Podiatric, Vascular, Plastics, and Infectious Diseases). Treatment effectiveness was determined by examining documentation at follow-up. We also looked at the number of Outpatient Department treatments at the Wound Care Center for the periods 2018-2019 and 2020-2021. The shift of patients from the Emergency Department/Inpatient Department to the Outpatient Department/Wound Care Center was made possible by the use of the novel, streamlined, safe, Food and Drug Administration (FDA)-approved, well-tolerated antibiotic Dalbavancin. Dalbavancin is not prescribed for gram-negative infections, or for random prescribing, contamination, colonization, or prophylaxis. Dalbavancin has a low infusion reaction, low toxicity, long half-life, and low incidence of adverse reactions. Use of this medication was helpful for decreasing the inpatient burden in our facility.

Validation of quantitative susceptibility mapping with Perls' iron staining for subcortical gray matter.

Quantitative susceptibility mapping (QSM) measures bulk susceptibilities in the brain, which can arise from many sources. In iron-rich subcortical gray matter (GM), non-heme iron is a dominant susceptibility source. We evaluated the use of QSM for iron mapping in subcortical GM by direct comparison to tissue iron staining. We performed in situ or in vivo QSM at 4.7 T combined with Perls' ferric iron staining on the corresponding extracted subcortical GM regions. This histochemical process enabled examination of ferric iron in complete slices that could be related to susceptibility measurements. Correlation analyses were performed on an individual-by-individual basis and high linear correlations between susceptibility and Perls' iron stain were found for the three multiple sclerosis (MS) subjects studied (R(2) = 0.75, 0.62, 0.86). In addition, high linear correlations between susceptibility and transverse relaxation rate (R2*) were found (R(2) = 0.88, 0.88, 0.87) which matched in vivo healthy subjects (R(2) = 0.87). This work validates the accuracy of QSM for brain iron mapping and also confirms ferric iron as the dominant susceptibility source in subcortical GM, by demonstrating high linear correlation of QSM to Perls' ferric iron staining.

Multiple sclerosis: validation of MR imaging for quantification and detection of iron.

PURPOSE: To investigate the relationship between iron staining and magnetic resonance (MR) imaging measurements in postmortem subjects with multiple sclerosis (MS). MATERIALS AND METHODS: Institutional ethical approval was obtained, and informed consent was obtained from the subjects and/or their families. Four MR imaging methods based on transverse relaxation (T2 weighting, R2 mapping, and R2* mapping) and phase imaging were performed by using a 4.7-T system in three in situ postmortem patients with MS less than 28 hours after death and in one in vivo patient 1 year before death. Iron staining with the Perls iron reaction was performed after brain extraction. Region-of-interest measurements from six subcortical gray matter structures were obtained from MR imaging and then correlated with corresponding locations on photographs of iron-stained pathologic slices by using a separate linear least-squares regression in each subject. Iron status of white matter lesions, as determined by staining, was compared with appearance on MR images. RESULTS: R2* mapping had the highest intrasubject correlations with iron in subcortical gray matter (R(2) = 0.857, 0.628, and 0.685; all P < .001), while R2 mapping (R(2) = 0.807, 0.615, 0.628, and 0.489; P < .001 and P = .001, .034, and .001, respectively), phase imaging (R(2) = 0.672, 0.441, 0.596, 0.548; all P ≤ .001), and T2-weighted imaging (R(2) = 0.463, 0.582, 0.650, and 0.551; all P < .001) had lower but still strong correlations. Within lesions, hypointense areas on phase images did not always represent iron. A hyperintense rim surrounding lesions on R2* maps was only present with iron staining, yet not all iron-staining lesions had R2* rim hyperintensity. CONCLUSION: All four MR imaging methods had significant linear correlations with iron and could potentially be used to determine iron status of subcortical gray matter structures in MS, with R2* mapping being preferred. A reliable method of determining iron status within MS lesions was not established.

Resurrection of the Achilles tenotomy.

This study evaluates the results of treating neuropathic diabetes mellitus (DM) foot ulcers with Achilles tendon percutaneous complete tenotomy. To the authors' knowledge this study is the largest of this nature to date. One hundred twenty-seven patients with Wagner Grade 1 to 4 foot ulcers were treated with percutaneous Achilles complete tenotomy between January 2007 and December 2010. All procedures were performed under local anesthesia and sedation in the operating room. The foot was held in maximum dorsiflexion, while the tendon was cut and completely released. The surgical site was dressed in a well-padded sterile dressing and wrap. Patients steadily increased their tolerance to walking in a post-op shoe. One hundred twenty-one patients who underwent percutaneous complete tenotomy experienced healing of their ulcers. To date, no Achilles contracture recurrences have been reported. Three patients experienced treatment-related adverse events. An additional six patients had recalcitrant ulcers requiring further therapy. Our findings in 127 patients with neuropathic diabetic foot ulcers add further credence to the growing evidence that percutaneous complete tenotomy of the Achilles tendon is a viable approach to treat Wagner Grade 1 to 4 foot ulcers.

Neuropathology in Canada: overview of development and current status.

BACKGROUND: The expansion of neurosurgery and neurology in Montreal and Toronto in the early 20th century was th stimulus for the development of neuropathology in Canada. Rooted in the disciplines of the neurosciences and laboratory medicine, neuropathology evolved into an independent discipline with the founding of the Canadian Association of Neuropathologists in 1960, and the recognition as a specialty by the Royal College of Physicians and Surgeons in Canada in 1965, fostering the development of several successful training programs. Nonetheless, a paucity of data remains concerning the background of training, scopes of practice, and career paths. METHOD: We conducted a survey of all physicians in Canada who have either practiced neuropathology or undergone relevant training. RESULTS: In 2009, 53 physicians were engaged in the practice of neuropathology, either exclusively or a substantial proportion of their time. Most work in tertiary hospitals, but a few service non-academic medical centers. Three routes of training were identified: direct from medical school (often with relevant research training), indirect from another clinical neuroscience specialty, and following or in conjunction with certification in one of the other pathology specialties. Practice profiles differ slightly, and some of the neuropathologists entering from pathology have mixed anatomical pathology/neuropathology responsibilities. Many of those with prior exposure in the neurosciences are more productive with regard to research and publications. CONCLUSIONS: Existing multiple options for neuropathology training have facilitated recruitment and allowed development of a mosaic of specialists able to fulfill the diversity of needs in Canadian medical and scientific communities.

Mutations in TPM3 are a common cause of congenital fiber type disproportion.

OBJECTIVE: Congenital fiber type disproportion (CFTD) is a rare form of congenital myopathy in which the principal histological abnormality is hypotrophy of type 1 (slow-twitch) fibers compared with type 2 (fast-twitch) fibers. To date, mutation of ACTA1 and SEPN1 has been associated with CFTD, but the genetic basis in most patients is unclear. The gene encoding alpha-tropomyosin(slow) (TPM3) is a rare cause of nemaline myopathy, previously reported in only five families. We investigated whether mutation of TPM3 is a cause of CFTD. METHODS AND RESULTS: We sequenced TPM3 in 23 unrelated probands with CFTD or CFTD-like presentations of unknown cause and identified novel heterozygous missense mutations in five CFTD families (p. Leu100Met, p.Arg168Cys, p.Arg168Gly, p.Lys169Glu, p.Arg245Gly). All affected family members that underwent biopsy had typical histological features of CFTD, with type 1 fibers, on average, at least 50% smaller than type 2 fibers. We also report a sixth family in which a recurrent TPM3 mutation (p.Arg168His) was associated with histological features of CFTD and nemaline myopathy in different family members. We describe the clinical features of 11 affected patients. Typically, there was proximal limb girdle weakness, prominent weakness of neck flexion and ankle dorsiflexion, mild facial weakness, and mild ptosis. The age of onset and severity varied, even within the same family. Many patients required nocturnal noninvasive ventilation despite remaining ambulant. INTERPRETATION: Mutation of TPM3 is the most common cause of CFTD reported to date.

Hemorrhagic presentations of cerebellar pilocytic astrocytomas in children resulting in death: report of 2 cases.

Acute hemorrhagic presentation in pilocytic astrocytomas (PAs) has become increasingly recognized. This type of presentation poses a clinically emergent situation in those hemorrhages arising in PAs of the cerebellum, the most frequent site, because of the limited capacity of the posterior fossa to compensate for mass effect, predisposing to rapid neurological deterioration. As examples, we describe two cases of fatal hemorrhagic cerebellar PAs: one of a child with a slowly growing stereotypical WHO Grade I PA with a 1-year period of symptomatology that preceded a rapid clinical deterioration, and another of an asymptomatic child having a PA variant, presenting with progressive obtundation following a presumed Valsalva event. These two scenarios parallel previous reports in the literature of either a setting of progressive expression of cerebellar dysfunction and transient episodes of raised intracranial pressure (ICP), or abrupt onset of features of increased ICP in a previously well child. The literature is further reviewed for a current understanding of the factors that predispose, initiate and propagate bleeding, with specific reference to the role of vascular endothelial growth factor and other angiogenic agents in the genesis and stability of the vasculature in PAs. In this context, we propose that obliterative vascular mural hyalinization with associated altered flow dynamics and microaneurysm formation was the pathogenesis of the hemorrhage in our first case. In the second case, large tumor size, increased growth rate, looseness of the background myxoid matrix, and thinness of the tumor blood vessels with calcospherite deposition predisposed to vascular leakage and bleeding concurrent with sudden increases in intravascular hydrostatic pressure. In that cerebellar PAs are common, this report underscores the importance of considering in the differential diagnosis the possibility of a spontaneous hemorrhage in a posterior fossa PA in a child presenting with a sudden neurological ictus and raised ICP.

Death after late failure of third ventriculostomy in children. Report of three cases.

Late failure following successful third ventriculostomy for obstructive hydrocephalus is rare, and death caused by failure of a previously successful third ventriculostomy has been reported only once. The authors present three patients who died as a result of increased intracranial pressure (ICP) after late failure of a third ventriculostomy. Through a collaborative effort, three patients were identified who had died following third ventriculostomy at one of the authors' institutions. A 13-year-old girl with neurofibromatosis Type 1 underwent third ventriculostomy for obstructive hydrocephalus caused by a tectal lesion. Three years later her condition deteriorated rapidly over the course of 6 hours and she was found dead at home. A 4-year-old boy treated with third ventriculostomy for aqueductal stenosis presented 2 years postoperatively with symptoms of increased ICP. This patient suffered a cardiorespiratory arrest while under observation and died despite external ventricular drainage. A 10-year-old boy with previous ventriculoperitoneal (VP) shunt placement underwent conversion to a third ventriculostomy and shunt removal. Eight months after the procedure his condition deteriorated. with evidence of raised ICP, and he underwent emergency insertion of another VP shunt, but remained in a vegetative state and died of complications. Neuropathological examinations in two cases demonstrated that the third ventriculostomy was not patent, and there was also evidence of increased ICP. Late failure of third ventriculostomy resulting in death is a rare complication. Delay in recognition of recurrent ICP symptoms and a false feeling of security on the part of family and caregivers because of the absence of a shunt and the belief that the hydrocephalus has been cured may contribute to fatal complications after third ventriculostomy. Patients with third ventriculostomies should be followed in a manner similar to patients with cerebrospinal fluid shunts.

Manchineel dermatitis in North American students in the Caribbean.

We report an outbreak of Manchineel dermatitis and ophthalmitis in four students from North America who visited the island of Bequia, West Indies. The exposure resulted from taking shelter during a rain storm under a Manchineel tree. Manchineel exposure and ingestion can lead to severe and even fatal disease.

An unusual presentation of copper metabolism disorder and a possible connection with Niemann-Pick type C.

Abnormal copper metabolism has been linked with neurological disorders, such as Wilson and Menkes disease. Another disorder causing symptoms similar to copper metabolism disorder is Niemann-Pick type C. However, a definite pathophysiological connection between Niemann-Pick type C and copper metabolism disorders has never been established. The authors present an adolescent with an unusual presentation of copper deficiency-dysarthria, ataxia, and vertical gaze paresis, without significant cognitive degeneration or pathological magnetic resonance imaging (MRI). The patient was found to carry 2 mutations in the NPC1 gene. A possible link, explaining how copper deficiency might induce the Niemann-Pick phenotype might involve overproduction of cholesterol and inhibition of acid sphingomyelinase. We suggest that copper metabolism disorders be included in the differential diagnosis for ataxia and dysarthria, even in cases with unusual presentations. Moreover, should the connection between copper and Niemann-Pick be validated, screening for copper metabolism disorders may be advisable in Niemann-Pick type C patients and vice-versa.

Neuroinflammation and demyelination in multiple sclerosis after allogeneic hematopoietic stem cell transplantation.

OBJECTIVE: To evaluate the effects of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on the brains of persons with and without multiple sclerosis (MS) by means of postmortem histopathological examination. DESIGN: Postmortem histopathology, case studies, and case-control studies. Patients Four patients with MS who died at a median of 4.5 months (range, 3-9 months) after allo-HSCT for a concomitant hematologic malignant neoplasm; 5 patients without MS who died at a median of 10.0 months (1-29 months) after allo-HSCT; and 5 control subjects without MS who did not undergo allo-HSCT. SETTING: Referral centers. Intervention Allogeneic hematopoietic stem cell transplantation. MAIN OUTCOME MEASURES: Morphological features and immunohistochemical features, including the quantitative measures of chronic inflammatory cells. RESULTS: Demyelinating and inflammatory activities of MS persisted after allo-HSCT in all of the patients with MS. Active and chronic active MS lesions exhibited significantly higher numbers of CD3+ T cells and CD8+ cytotoxic T cells and significantly higher scores of CD68+ microglia/macrophages than did chronic inactive lesions or normal-appearing white matter. The normal-appearing brains of allo-HSCT recipients who did not have MS were found to have significantly higher numbers of CD3+ T cells and CD8+ cytotoxic T cells and higher scores of CD68+ microglia/macrophages compared with the controls; however, no demyelination was identified in these non-MS samples. CONCLUSION: Allo-HSCT fails to halt the demyelination and inflammation of MS.

Case Report: Exotropia Surgery in CPEO.

Exotropia in a patient with CPEO was managed with bilateral medial rectus resections. Molecular genetic analysis of DNA from a skeletal muscle biopsy confirmed a deletion of the mitochondrial DNA. The resected muscle tendon was subjected to transmission electron microscopy, revealing muscle fibre variability and ragged red fibres with mitochondrial abnormalities.