Snowed In: A Case Report on the Utilization of Ultrasound in the Diagnosis of Fractures.

The standard convention for diagnosing bone fractures is through radiography. However, radiography can miss fractures depending on the type of injury or if human error is present. This may be due to improper patient positioning leading to superimposing bones being captured in the image, obscuring pathology. As of late, ultrasound has been gaining traction in terms of its utilization for diagnosing fractures, which radiography can miss at times. Here we present a case of a 59-year-old female who was diagnosed using ultrasound with an acute fracture that was initially missed on X-ray. We present a case of a 59-year-old female with a past medical history significant for osteoporosis who presented to an outpatient clinic for evaluation of acute left forearm pain. She reported sustaining a mechanical fall forward to the ground three weeks before bracing herself with her forearms, immediately developing left upper extremity pain lateralized to the forearm. Upon initial evaluation, forearm radiographs were obtained and showed no evidence of acute fractures. She then underwent a diagnostic ultrasound that showed an obvious fracture of the proximal radius, distal to the radial head. Upon reviewing initial radiograph films, it was evident that the proximal ulna was superimposed over the radius fracture as a proper neutral anteroposterior view of the forearm was not taken. The patient then underwent a computed tomography (CT) scan of her left upper extremity, which confirmed the presence of a healing fracture. We present a case in which ultrasound is an excellent adjunct when a fracture cannot be identified on plain film radiography. Its utilization should be well-known and considered more often in the outpatient setting.

Osteopathic Manipulative Treatment and the Management of Headaches: A Scoping Review.

Headaches have been studied and treated since nearly 7,000 BC because of their significant global impact. Current headache treatment modalities are various and have a wide variety of targets, but medications are the most common. Since conventional medical treatments have several side effects, alternative remedies such as osteopathic manipulative treatment (OMT) should be considered. OMT can assist in the management of various health conditions, such as low back pain, neck pain, and headaches. The purpose of this scoping review is to evaluate recent findings regarding the efficacy of OMT modalities in the management of headaches such as tension-type headaches (TTH) and migraines. This study was designed as a scoping review to gather evidence on the efficacy of OMT modalities in the management of headaches. Following PRISMA guidelines, four databases were used to search for articles published between 2010 and 2022 that reported the use of OMT and manual therapy for TTH and migraines. Databases used include Embase, PubMed, Medline, and Web of Science. The following keywords were used: treatment, therapy, Headache, migraine, craniosacral, muscle energy, myofascial release, trigger point, osteopathic, and manipulation. The initial search yielded 473 unique articles after removing duplicates. After screening based on the inclusion and exclusion criteria, and after further analysis, 15 articles were selected. Data reports of OMT and manual therapy efficacy and/or effectiveness in treating TTH and migraine were analyzed. Articles included were randomized control studies (13 of 15, 86.6%), one pilot study (one of 15, 6.7%), and one case series (one of 15, 6.7%), which were divided into TTH (nine of 15, 60%) and Migraine Headaches (six of 15, 40%). All articles reported significant headache improvement in at least one measurement. Of all treatments analyzed, single technique interventions (seven of 15, 47%) and multiple technique interventions (eight of 15, 53%) were identified. Among the techniques used, Myofascial Release was the most common (nine of 15, 60%). The articles presented provide evidence of the significant benefits of manual therapy. Because of the limitations of traditional medicine, OMT can be used either as an alternative or adjuvant therapy for headaches. Evidence suggests the positive impact it can provide on headache management, but the number of randomized control trials and population samples should be increased to support its recommendation. This demonstrates how different osteopathic techniques can provide therapeutic effects on TTH, MH, and potentially other types of headaches. A preference for myofascial release was observed, which can be due to the fast relief from the physiologic effect on tissue movement. This review study demonstrates the benefits OMT has on decreasing headache frequency, intensity, and duration in TTH and migraines. OMT has shown to be beneficial, especially for patients seeking alternative non-pharmaceutical and non-invasive treatments. Further studies are needed to evaluate the effects of different OMT techniques, and different combinations of treatments, on other types of headaches.

Ibrutinib in Refractory or Relapsing Primary Central Nervous System Lymphoma: A Systematic Review.

Primary Central Nervous System Lymphoma (PCNSL) is a rare variant of Non-Hodgkin Lymphoma (NHL) representing 1-2% of all NHL cases. PCNSL is defined as a lymphoma that occurs in the brain, spinal cord, leptomeninges, or eyes. Efforts to treat PCNSL by traditional chemotherapy and radiotherapy have generally been unsuccessful as a significant proportion of patients have frequent relapses or are refractory to treatment. The prognosis of patients with Refractory or Relapsed (R/R) PCNSL is abysmal. The optimal treatment for R/R PCNSL is poorly defined as there are only a limited number of studies in this setting. Several studies have recently shown that ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, has promising results in the treatment of R/R PCNSL. However, these are preliminary studies with a limited sample size. In this systematic review, we explored and critically appraised the evidence about the efficacy of the novel agent ibrutinib in treating R/R PCNSL.

Updates on the Role of Spinal Cord Stimulation in the Management of Non-Surgical Chronic Lower Back Pain.

Studies have shown that spinal cord stimulation (SCS) therapy is effective in the management of chronic low back pain. It plays a role by minimizing the intensity of chronic pain, improving the quality of life index, reducing the intake of narcotic analgesics, and increasing the functional improvement in the working environment. However, spinal cord stimulation therapy is not universal because of the complications in the procedure itself, the invasive nature of the treatment, and cost-effectiveness. Therefore, the proper selection of the patients is necessary to get the maximum benefit from the treatment. The study's main objective is to determine the role of spinal cord stimulation in treating non-surgical patients with chronic low back pain. The article will review the mechanism, outcomes, efficacy, predisposing factors in the success and failure of the treatment and indications, contraindications, and selection of patients undergoing spinal cord stimulation therapy. A manual search of the literature was done using databases like Google Scholar and PubMed using the keywords: spinal cord, stimulation, chronic, and low back pain. A total of 37 articles were included in the study after considering the inclusion and exclusion criteria. Spinal cord stimulation therapy effectively treats refractory lower back pain, considering the technology and mechanism of action. The authors conclude that spinal cord stimulation therapy can be used to manage chronic low back pain, other neuropathic pain, and ischemic pain when other standard treatment methods have failed and the pain persisted for more than six months.

The role of 5-aminolevulinic acid in brain tumor surgery: a systematic review.

Recently, 5-aminolevulinic acid (5-ALA) has been utilized as an adjuvant to the surgical resection of primary brain tumors and metastases. We conducted a systematic review of the literature to further understand the role of 5-ALA in neurosurgery. Our goal was to identify the utility of 5-ALA during resection by evaluating its sensitivity and specificity for different tumor types, as well as the extent of tumor resection achieved while using 5-ALA. A search of the literature was conducted using the PubMed database for the period January 1990 through May 2014. Surgical series in which 5-ALA was used for brain neoplasm resections were evaluated for tumor histology, sensitivity, specificity, extent of resection, complications, and outcomes. Twenty-two series, involving 1163 patients, were included in our review. 5-ALA sensitivity was highest in high-grade gliomas (85 %) and meningiomas (81 %). 5-ALA specificity was high in meningiomas (100 %), as well as metastases (84 %) and high-grade gliomas (82 %). Gross total resection (GTR) was achieved using 5-ALA in 66.2 % of all gliomas and 69.6 % of meningiomas, regardless of histological subtype. 5-ALA may be a useful tool in increasing the extent of resection and achieving GTR in intracranial tumors. The resection of tumors for which 5-ALA has high sensitivity and specificity, such as high-grade gliomas, may lead to an increase in extent of resection when compared to operations using only standard white light. Further evidence for the use of 5-ALA in meningiomas and certain subtypes of metastases may be needed to qualify its efficacy.

The role of adjuvant radiotherapy after gross total resection of atypical meningiomas.

BACKGROUND: Atypical meningiomas (AMs) frequently recur after gross total resection (GTR). OBJECTIVE: We conducted a meta-analysis to evaluate the benefit of adjuvant therapy after GTR of AMs. METHODS: A PubMed/MEDLINE search identified studies detailing AMs treated by GTR alone or GTR and adjuvant radiotherapy (RT) published between 1984 and 2012. Original data from 14 retrospective studies were combined and analyzed. Odds ratio (OR) and χ(2) testing were used when appropriate. Selected datasets were used to generate each variable, where available. RESULTS: A total of 757 patients (male/female ratio 9:10) with AMs were included; 72.52% (n = 549) of AMs were treated by GTR alone, and 27.47% (n = 208) underwent adjuvant RT after GTR to a median dose of 54 Gy. The crude recurrence rate was twice as high without adjuvant RT (33.7% vs. 15%, P = 0.005). The 1-year local control rate was 90% for GTR and 97% for GTR + RT (OR = 3.36, P = 0.11). The median 5-year local control rate was 62% for GTR and 73% for GTR + RT, respectively (OR = 1.71, P = 0.06). The 5-year overall survival for each group was 90% (OR = 0.97, P = 0.95). A total of 85% of recurrences were salvaged, 33% by RT and 67% by surgery. Radiation-related toxicity was <10%, at a median follow-up of 42 months. CONCLUSIONS: Postoperative RT for AMs may decrease risk for relapse of disease and improve local control, although most tumors are salvageable with surgery or radiation. Although the data suggest little or no impact of postoperative RT on survival, further investigation regarding the long-term efficacy and toxicity of radiation is warranted.

The role of whole-brain radiation therapy after stereotactic radiation surgery for brain metastases.

The benefit of whole-brain radiation therapy (WBRT) following stereotactic radiation surgery (SRS) for brain metastases is controversial. We conducted a systematic analysis of published literature to explore the outcome of brain metastases treated with SRS and WBRT versus SRS alone using PubMed and MEDLINE. Outcomes including survival, control, salvage therapy, and other quality of life measures were reported. Three randomized controlled trials involving 389 patients with 1 to 4 brain metastases were selected. In 2 of these trials (n = 190), the mean 1-year survival was 33.2% for SRS + WBRT and 38.7% for SRS alone (P = .5233); 1-year local control was 89% for SRS + WBRT and 71% for SRS alone (P < .001). Mean crude distant recurrence rate for SRS + WBRT was 36.6% and 54% for SRS alone (P < .001). Patients without WBRT were over 3 times more likely to require salvage therapy (P < .001). The addition of WBRT was associated with a decreased health-related quality of life assessment, mini mental status exam, and Hopkins Verbal Learning Test (P < .05). Five retrospective studies (n = 1122) were also included in a separate analysis and yielded findings that supported results from the randomized trials. Our systematic analysis demonstrates that adjuvant WBRT following SRS for the treatment of oligometastases in the brain is more effective at controlling local and distant recurrence than SRS alone, but there is no apparent benefit for survival or symptomology. The proven cognitive decline and neurotoxicity present with WBRT should be weighed against the benefit of local control. Prognosis of brain metastasis is poor regardless of current treatment and further exploration for alternative adjuvant treatment for SRS is warranted.

Intracellular matrix metalloproteinase-2 (MMP-2) regulates human platelet activation via hydrolysis of talin.

Matrix metalloproteinase (MMP) activity is generally associated with normal or pathological extracellular processes such as tissue remodelling in growth and development or in tumor metastasis and angiogenesis. Platelets contain at least three MMPs, 1, 2 and 9 that have been reported to stimulate or inhibit agonist-induced platelet aggregation via extracellular signals. The non-selective Zn+2 chelating MMP inhibitor, 1,10-phenanthroline, and the serine protease inhibitor, AEBSF, were found to inhibit all tested agonist-induced platelet aggregation reactions. In vitro analysis demonstrated that 1,10-phenanthroline completely inhibited MMP-1,2,and 9 but had little to no effect on calpain activity while the converse was true with AEBSF. We now demonstrate that MMP-2 functions intracellularly to regulate agonist-induced platelet aggregations via the hydrolytic activation of talin, the presumed final activating factor of glycoprotein (GP)IIb/IIIa integrin (the inside-out signal). Once activated GPIIb/IIIa binds the dimeric fibrinogen molecule required for platelet aggregation. The active intracellular MMP-2 molecule is complexed with JAK 2/STAT 3, as demonstrated by the fact that all three proteins are co-immunoprecipitated with either anti-JAK 2, or anti-STAT 3 antibodies and by immunofluorescence studies. The MMP-2 platelet activation pathway can be synergistically inhibited with the non-selective MMP inhibitor, 1,10-phenanthroline, plus a JAK 2 inhibitor. This activation pathway is distinct from the previously reported calpain-talin activating pathway. The identification of a new central pathway for platelet aggregation presents new potential targets for drug regulation and furthers our understanding of the complexity of platelet activation mechanisms.

Ablation of a Ca2+-activated K+ channel (SK2 channel) results in action potential prolongation in atrial myocytes and atrial fibrillation.

Small conductance Ca(2+)-activated K(+) channels (SK channels) have been reported in excitable cells, where they aid in integrating changes in intracellular Ca(2+) (Ca(2+)(i)) with membrane potential. We have recently reported the functional existence of SK2 channels in human and mouse cardiac myocytes. Moreover, we have found that the channel is predominantly expressed in atria compared to the ventricular myocytes. We hypothesize that knockout of SK2 channels may be sufficient to disrupt the intricate balance of the inward and outward currents during repolarization in atrial myocytes. We further predict that knockout of SK2 channels may predispose the atria to tachy-arrhythmias due to the fact that the late phase of the cardiac action potential is highly susceptible to aberrant excitation. We take advantage of a mouse model with genetic knockout of the SK2 channel gene. In vivo and in vitro electrophysiological studies were performed to probe the functional roles of SK2 channels in the heart. Whole-cell patch-clamp techniques show a significant prolongation of the action potential duration prominently in late cardiac repolarization in atrial myocytes from the heterozygous and homozygous null mutant animals. Moreover, in vivo electrophysiological recordings show inducible atrial fibrillation in the null mutant mice but not wild-type animals. No ventricular arrhythmias are detected in the null mutant mice or wild-type animals. In summary, our data support the important functional roles of SK2 channels in cardiac repolarization in atrial myocytes. Genetic knockout of the SK2 channels results in the delay in cardiac repolarization and atrial arrhythmias.