Clinical Anatomy of the Ligament of the Head of Femur

The ligament of the head of femur (LHF) has gained clinical attention recently and is reported to contribute to hip stability. This study explores its morphology and morphometry, information that may help inform surgical decision making. Gross anatomical dissections were undertaken on 229 embalmed hips from European (n = 105) and Thai (n = 124) adult cadavers to examine LHF anatomy. Ligament morphometry was statistically compared at different sites, between sexes and sides. The origin of ligamental arteries and absence of the ligament were documented. The LHF was pyramidal or quadrangular in shape. Sub‐synovial fibrous bands originated from the transverse acetabular ligament, edges of the acetabular notch, and acetabular floor; less frequently from the hip joint capsule. Distally, the ligament flattened and converged onto the fovea capitis. The ligament was 22.3 ± 4.4 mm long and was significantly wider (P = 0.001) and thicker (P = 0.0003) at the fovea, compared to its mid‐zone. Branches of the obturator artery entered the acetabular foramen inferomedially and penetrated the middle third of the LHF. Blood vessels ran within the LHF and appeared to enter the fovea. The ligament was absent in 2.8% of Thai hips and there were no significant sex or side differences in ligament dimensions. The morphology of the LHF is complex. While individual variation was apparent, blood vessels were seen in the distal ligament. Precise information on LHF morphometry and attachment sites will help inform appropriate graft dimensions and choice of fixation sites necessary for ligament reconstruction. Clin. Anat., 2018. © 2018 Wiley Periodicals, Inc. Clin. Anat., 2018. © 2018 Wiley Periodicals, Inc.     

Multicenter Evaluation of 434 Hospital Deaths From COVID-19: How Can We Improve End-of-Life Care During a Pandemic?

ContextThe pandemic has substantially increased the workload of hospital palliative care providers, requiring them to be responsive and innovative despite limited information on the specific end of life care needs of patients with COVID-19. Multi-site data detailing clinical characteristics of patient deaths from large populations, managed by specialist and generalist palliative care providers are lacking.ObjectivesTo conduct a large multicenter study examining characteristics of COVID-19 hospital deaths and implications for care.MethodsA multi-center retrospective evaluation examined 434 COVID-19 deaths in 5 hospital trusts over the period March 23, 2020 to May 10, 2020.ResultsEighty three percent of patients were over 70.32% were admitted from care homes. Diagnostic timing indicated over 90% of those who died contracted the virus in the community. Dying was recognized in over 90% of patients, with the possibility of dying being identified less than 48 hours from admission for a third. In over a quarter, death occurred less than 24 hours later. Patients who were recognized to be dying more than 72 hours prior to death were most likely to have access to medication for symptom control.ConclusionThis large multicenter study comprehensively describes COVID-19 deaths throughout the hospital setting. Clinicians are alert to and diagnose dying appropriately in most patients. Outcomes could be improved by advance care planning to establish preferences, including whether hospital admission is desirable, and alongside this, support the prompt use of anticipatory subcutaneous medications and syringe drivers if needed. Finally, rapid discharges and direct hospice admissions could better utilize hospice beds and improve care.     

Delusional parasitosis as presenting symptom of occipital lobe cerebrovascular accident

Delusional parasitosis manifests as a fixed, false belief that an individual is infested by living organisms. Primary delusional parasitosis is a psychiatric disorder with the delusion as an isolated manifestation, whereas secondary delusional parasitosis is a delusion occurring secondary to a psychiatric disorder, substance use, or medical illness. A 62-year-old woman with no psychiatric history presented to the Emergency Department with two to three months of “whole body itching” and seeing small insects crawling on her skin and in her hair. Exam of her skin and scalp was notable for no appreciable lesions, rashes, excoriations, or insects. Her neurologic exam was notable for full visual fields, and no localizing deficits. A non-contrast head CT demonstrated a nonspecific heterogeneous low-attenuation lesion within the medial right occipital lobe, and a follow up MRI confirmed a right posterior cerebral artery distribution subacute infarction. She was admitted for two days, and ultimately was discharged on aspirin and atorvastatin for secondary prevention. An emergency physician should remain vigilant in his/her assessment of patients with seemingly psychiatric symptoms, in particular elderly patients with no known psychiatric illnesses. Neuroimaging should be amongst studies considered in the evaluation of elderly patients presenting with new onset psychiatric complaints.     

Galectin-3 modulates postnatal subventricular zone gliogenesis

Postnatal subventricular zone (SVZ) neural stem cells generate forebrain glia, namely astrocytes and oligodendrocytes. The cues necessary for this process are unclear, despite this phase of brain development being pivotal in forebrain gliogenesis. Galectin-3 (Gal-3) is increased in multiple brain pathologies and thereby regulates astrocyte proliferation and inflammation in injury. To study the function of Gal-3 in inflammation and gliogenesis, we carried out functional studies in mouse. We overexpressed Gal-3 with electroporation and using immunohistochemistry surprisingly found no inflammation in the healthy postnatal SVZ. This allowed investigation of inflammation-independent effects of Gal-3 on gliogenesis. Loss of Gal-3 function via knockdown or conditional knockout reduced gliogenesis, whereas Gal-3 overexpression increased it. Gal-3 overexpression also increased the percentage of striatal astrocytes generated by the SVZ but decreased the percentage of oligodendrocytes. These novel findings were further elaborated with multiple analyses demonstrating that Gal-3 binds to the bone morphogenetic protein receptor one alpha (BMPR1α) and increases bone morphogenetic protein (BMP) signaling. Conditional knockout of BMPR1α abolished the effect of Gal-3 overexpression on gliogenesis. Gain-of-function of Gal-3 is relevant in pathological conditions involving the human forebrain, which is particularly vulnerable to hypoxia/ischemia during perinatal gliogenesis. Hypoxic/ischemic injury induces astrogliosis, inflammation and cell death. We show that Gal-3 immunoreactivity was increased in the perinatal human SVZ and striatum after hypoxia/ischemia. Our findings thus show a novel inflammation-independent function for Gal-3; it is necessary for gliogenesis and when increased in expression can induce astrogenesis via BMP signaling.     

Comparative analgesic efficacy of pregabalin administered according to either a prevention protocol or an intervention protocol in rats with cisplatin‐induced peripheral neuropathy

Chemotherapy‐induced peripheral neuropathy (CIPN) is a type of peripheral neuropathic pain that may be dose‐limiting in patients administered potentially curative cancer chemotherapy dosing regimens. In cancer survivors, persistent CIPN adversely affects patient quality of life and so adjuvant drugs (anticonvulsants eg pregabalin or antidepressants eg amitriptyline) are recommended for the relief of CIPN. However, most studies in rodent models of CIPN involve administration of single bolus doses of adjuvant drugs to assess pain‐relieving efficacy. Hence this study was designed to assess the efficacy of pregabalin administered to CIPN‐rats according to either a prevention or an intervention protocol. Groups of male Sprague‐Dawley rats received four single intraperitoneal bolus doses of cisplatin at 3 mg/kg at once‐weekly intervals to induce CIPN. For the prevention protocol, oral pregabalin (or vehicle) was administered to CIPN‐rats once‐daily for 21 consecutive days from day 0 to day 20 inclusive. For the intervention protocol, oral pregabalin was administered once‐daily for 21 consecutive days from day 28 to day 48, inclusive. Mechanical allodynia and mechanical hyperalgesia in the bilateral hindpaws were assessed just prior to each dose of cisplatin and at least once weekly until study completion (day 27, prevention protocol; or day 48, intervention protocol). Mechanical allodynia and mechanical hyperalgesia were also determined at the time of peak effect at about 2 hours post pregabalin/vehicle administration, once weekly until study completion. For the prevention protocol in CIPN‐rats, pregabalin alleviated mechanical hyperalgesia but not mechanical allodynia. For the intervention protocol, pregabalin alleviated both mechanical allodynia and mechanical hyperalgesia in the hindpaws.     

Aberrant accrual of BIN1 near Alzheimer’s disease amyloid deposits in transgenic models

Bridging integrator 1 (BIN1) is the most significant late‐onset Alzheimer’s disease (AD) susceptibility locus identified via genome‐wide association studies. BIN1 is an adaptor protein that regulates membrane dynamics in the context of endocytosis and membrane remodeling. An increase in BIN1 expression and changes in the relative levels of alternatively spliced BIN1 isoforms have been reported in the brains of patients with AD. BIN1 can bind to Tau, and an increase in BIN1 expression correlates with Tau pathology. In contrast, the loss of BIN1 expression in cultured cells elevates Aβ production and Tau propagation by insfluencing endocytosis and recycling. Here, we show that BIN1 accumulates adjacent to amyloid deposits in vivo. We found an increase in insoluble BIN1 and a striking accrual of BIN1 within and near amyloid deposits in the brains of multiple transgenic models of AD. The peri‐deposit aberrant BIN1 localization was conspicuously different from the accumulation of APP and BACE1 within dystrophic neurites. Although BIN1 is highly expressed in mature oligodendrocytes, BIN1 association with amyloid deposits occurred in the absence of the accretion of other oligodendrocyte or myelin proteins. Finally, super‐resolution microscopy and immunogold electron microscopy analyses highlight the presence of BIN1 in proximity to amyloid fibrils at the edges of amyloid deposits. These results reveal the aberrant accumulation of BIN1 is a feature associated with AD amyloid pathology. Our findings suggest a potential role for BIN1 in extracellular Aβ deposition in vivo that is distinct from its well‐characterized function as an adaptor protein in endocytosis and membrane remodeling.     

Linking Individuals with Substance Use Disorders (SUDs) in Primary Care to SUD Treatment: the Recovery Management Checkups–Primary Care (RMC-PC) Pilot Study

Linking individuals in primary care settings with substance use disorders (SUDs) to SUD treatment has proven to be challenging, despite the widespread use of Screening, Brief Intervention, and Referral to Treatment (SBIRT). This paper reports findings from a pilot study that examined the efficacy of the Recovery Management Checkups intervention adapted for primary care settings (RMC-PC), for assertively linking and engaging patients from Federally Qualified Health Centers into SUD treatment. Findings showed that patients in the RMC-PC (n=92) had significantly higher rates of SUD treatment entry and received more days of SUD treatment compared with those who receive the usual SBIRT referral (n=50). Receipt of RMC-PC had both direct and indirect effects, partially mediated through days of SUD treatment, on reducing days of drug use at 6 months post intake. RMC-PC is a promising intervention to address the need for more assertive methods for linking patients in primary care to SUD treatment.     

Physical property investigation of contemporary glass ionomer and resin-modified glass ionomer restorative materials

Objectives

The objective of this study was to investigate selected physical properties of nine contemporary and recently marketed glass ionomer cement (GIC) and four resin-modified glass ionomer cement (RMGI) dental restorative materials.

Materials and methods

Specimens (n = 12) were fabricated for fracture toughness and flexure strength using standardized, stainless steel molds. Testing was completed on a universal testing machine until failure. Knoop hardness was obtained using failed fracture toughness specimens on a microhardness tester, while both flexural modulus and flexural toughness was obtained by analysis of the flexure strength results data. Testing was completed at 1 h, 24 h, 1 week, and then at 1, 3, 6, and 12 months. Mean data was analyzed with Kruskal-Wallis and Mann-Whitney (p = 0.05).

Results

Physical properties results were material dependent. Physical properties of the GIC and RMGI products were inferior at 1 h compared to that at 24 h. Some improvement in selected physical properties were noted over time, but development processes were basically concluded by 24 h. A few materials demonstrated improved physical properties over the course of the evaluation.

Conclusions

Under the conditions of this study:

1. 1.

   GIC and RMGI physical property performance over time was material dependent;

2. 2.

   Polyalkenoate maturation processes are essentially complete by 24 h;

3. 3.

   Although differences in GIC physical properties were noted, the small magnitude of the divergences may render such to be unlikely of clinical significance;

4. 4.

   Modest increases in some GIC physical properties were noted especially flexural modulus and hardness, which lends support to reports of a maturing hydrogel matrix;

5. 5.

   Overall, GIC product physical properties were more stable than RMGI;

6. 6.

   A similar modulus reduction at 6 months for both RMGI and GIC produced may suggest a polyalkenoate matrix change; and

7. 7.

   Globally, RMGI products demonstrated higher values of flexure strength, flexural toughness, and fracture toughness than GIC materials.

Clinical relevance

As compared to RMGI materials, conventional glass ionomer restorative materials demonstrate more stability in physical properties.