C5 palsy following esophageal diverticulum resection.

Background: C5 palsy (C5P) is a recognized potential postoperative complication of cervical spine surgery but has rarely been reported following an open esophageal diverticulectomy. Methods: A 61-year-old underwent an open esophageal diverticulectomy for symptomatic Zencker's diverticulum. Results: Postoperatively, she presented with right upper extremity weakness and sensory deficits consistent with a C5P that was later confirmed by electromyography. Conclusion: The potential for C5P after esophageal diverticulectomy for symptomatic Zencker's diverticulum is rare. Postoperative recognition and appropriate management are critical to recovery.

The impact of emergency department crowding and patient boarding on resident point-of-care ultrasound education.

Objectives: Emergency department (ED) crowding negatively affects patient care, but the effect on resident education has been difficult to quantify. We aimed to describe the relationship between ED crowding and residents' ability to meet point-of-care ultrasound (POCUS) education goals. Methods: We retrospectively reviewed medical records from November 2021 to June 2023 at an academic level 1 trauma center, where emergency medicine residents complete longitudinal POCUS scanning shifts throughout 3 years of training. Residents are expected to complete ≥14 scans per scanning shift. We assessed whether completing the goal POCUS scans on a scanning shift (success: ≥14 scans, near-success: 10‒13, failure: <10) was associated with the average National Emergency Department Overcrowding Scale (NEDOCS) score or patient boarding hours during each scanning shift. Ordinal logistic regression was performed, controlling for the type of POCUS device available and the presence of medical students, interns, ultrasound faculty, and multiple residents. Results: Over 125 scanning shifts, 1340 scans were performed. Residents met the expected number of POCUS scans for 26.4% of scanning shifts, with 34.4% near-success and 39.2% failure. The average NEDOCS was 157.4 ± 31.9. POCUS success was associated with a lower mean NEDOCS (142 vs. 169, p < 0.001). After controlling for covariates, every 10-point increase in NEDOCS was associated with 17% lower odds of achieving the goal (odds ratio [OR] = 0.83, 95% confidence interval [CI] 0.73‒0.94, p = 0.003). Other significant factors were having only one resident on a scanning shift, which was associated with lower odds of success (OR = 0.41, 95% CI 0.18‒0.97, p = 0.043), and having a cart-based POCUS device available in addition to a handheld POCUS device, which was associated with higher odds of success (OR = 13.58, 95% CI 5.53‒33.38, p < 0.001). Conclusion: As ED crowding increased, residents were increasingly likely to fail to meet their POCUS education goals.

Metastatic choroid plexus papilloma presenting as a sellar mass: A case report and literature review.

Background: Choroid plexus papillomas (CPPs) are rare neoplasms arising from choroid plexus epithelium representing <1% of all intracranial tumors. Symptoms vary based on location and regional mass effect; however, hydrocephalus is common due to cerebrospinal fluid flow obstruction and/or overproduction. Distant site metastasis or de novo formation in extraventricular sites is rare. Case Description: A 57-year-old female with a history of a 4th ventricular CPP status post resection in 2004 and 2018 with subsequent gamma knife therapy in 2019 presented with increased thirst and urination. Since her initial surgery, she has experienced significant gait imbalance, diplopia, dysphagia, and right-sided hemiparesis and hemisensory loss. Magnetic resonance imaging revealed a new 1.5 × 1.8 cm suprasellar lesion. She underwent a left supraorbital craniotomy for tumor resection, with pathology revealing metastatic World Health Organization grade II CPP. Conclusion: Extraventricular manifestation of CPP is rare. De novo or metastatic involvement of the sella has seldom been reported. Treatment should target gross total surgical resection. Adjuvant chemotherapy and radiation may be useful in higher-grade lesions.

Intracranial malignant peripheral nerve sheath tumor: A case report and comprehensive literature review.

Background: Malignant peripheral nerve sheath tumors (MPNSTs) are rare malignant soft-tissue sarcomas arising from peripheral nerves. Little data exist regarding MPNST originating intracranially. Here, we present a 7th/8th nerve complex MPNST, discuss the treatment strategy and patient outcome, and provide a comprehensive review of existing literature. Methods: Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, PubMed and crossed references were queried, yielding 37 publications from 1952 to the present. Fifty-three cases of primary intracranial and extra-axial MPNST were identified. Results: We additionally report a 40-year-old female presented with acute onset dizziness and subsequent hearing loss with associated right-sided facial numbness. Magnetic resonance imaging revealed a 0.5 cm × 1.7 cm enhancing lesion within the right internal auditory canal extending into the cerebellopontine angle. The patient was initially treated with retro sigmoid craniotomy for tumor resection followed by a trans labyrinth approach for residual tumor resection. She completed adjuvant fractionated radiation therapy and underwent facial nerve transfer to restore complete hemifacial paralysis. The most common cranial nerves involved were V and VIII (43.4% each), with 66% of patients male and 34% female. The average age was 43.4 ± 17.4 years. The mean survival time for reported non-survivors after tissue diagnosis was 15 ± 4 months. Two-year survival for patients receiving gross total resection was 33.3% versus 22.8% with subtotal resection. Conclusion: MPNSTs comprise a group of highly aggressive neoplasms that rarely arise intracranially. Gross total surgical resection should be pursued when feasible.

Pseudogout mimicking cervical spine osteomyelitis and ventral epidural abscess: A case report and literature review.

Background: Calcium pyrophosphate deposition disease (CPPD), also known as "pseudogout," is a crystal deposition arthropathy involving the synovial and periarticular tissues. Pseudogout rarely presents in the axial spine. Here, we present the case of an 80-year-old female patient admitted after a mechanical fall, initially misdiagnosed on computed tomography (CT)/magnetic resonance studies with cervical osteodiscitis/ventral epidural abscess that proved to be pseudogout. Case Description: An 80-year-old female was admitted after a mechanical fall. The initial cervical CT scan showed multilevel degenerative changes with an acute C6 anterior wedge compression fracture, focal kyphosis, C5-6 disc space collapse, and endplate destruction. The magnetic resonance imaging showed marked contrast enhancement of the C5-6 vertebral bodies and disc space. An interventional radiology-guided biopsy of the C5-6 vertebral bodies and disc space was consistent with calcium pyrophosphate deposits, was diagnostic for pseudogout, and was negative for infection. She was managed conservatively with a rigid collar and seven days of oral prednisone. Conclusion: CPPD involvement in the axial spine is rare. Prompt pathologic diagnosis should be pursued to rule out an infectious process.

Facile Determination of the Poisson's Ratio and Young's Modulus of Polyacrylamide Gels and Polydimethylsiloxane.

Polyacrylamide hydrogels (PAH gel) and polydimethylsiloxane (PDMS, an elastomer) are two soft materials often used in cell mechanics and mechanobiology, in manufacturing lab-on-a-chip applications, among others. This is partly due to the ability to tune their elasticity with ease in addition to various chemical modifications. For affine polymeric networks, two (of three) elastic constants, Young's modulus (E), the shear modulus (G), and Poisson's ratio (ν), describe the purely elastic response to external forces. However, the literature addressing the experimental determination of ν for PAH (sometimes called PAA gels in the literature) and the PDMS elastomer is surprisingly limited when compared to the literature that reports values of the elastic moduli, E and G. Here, we present a facile method to obtain the Poisson's ratio and Young's modulus for PAH gel and PDMS elastomer based on static tensile tests. The value of ν obtained from the deformation of the sample is compared to the value determined by comparing E and G via a second independent method that utilizes small amplitude shear rheology. We show that the Poisson's ratio may vary significantly from the value for incompressible materials (ν = 0.5), often assumed in the literature even for soft compressible hydrogels. Surprisingly, we find a high degree of agreement between elastic constants obtained by shear rheology and macroscopic static tension test data for polyacrylamide hydrogels but not for elastomeric PDMS.

Platelet distribution width (PDW) as a significant correlate of COVID-19 infection severity and mortality.

SARS-CoV-2 infection may cause a wide spectrum of symptoms, from asymptomatic, to mild respiratory symptoms and life-threatening sepsis. Among the clinical laboratory biomarkers analyzed during COVID-19 pandemic, platelet indices have raised great interest, due to the critical involvement of platelets in COVID-19-related thromboinflammation. Through an electronic literature search on MEDLINE, CINAHL, PubMed, EMBASE, Web of Science, and preprint servers we performed and updated a systematic review aimed at providing a detailed analysis of studies addressing the potential clinical utility of platelet distribution width, platelet distribution width (PDW), in laboratory medicine, exploring the possible association between increased PDW levels, disease severity, and mortality in COVID-19. Our systematic review revealed a wide heterogeneity of COVID-19 cohorts examined and a lack of homogenous expression of platelet indices. We found that 75 % of studies reported significantly elevated PDW values in COVID-19 infected cohorts compared to healthy/non-COVID-19 controls, and 40 % of studies reported that patients with severe COVID-19 showed increased PDW values than those with less-than-severe illness. Interestingly, 71.4 % of studies demonstrated significant increased PDW values in non survivors vs. survivors. Overall, these results suggest that platelets are critically involved as major players in the process of immunothrombosis in COVID-19, and platelet reactivity and morphofunctional alterations are mirrored by PDW, as indicator of platelet heterogeneity. Our results confirm that the use of PDW as prognostic biomarkers of COVID-19 sepsis still remains debated due to the limited number of studies to draw a conclusion, but new opportunities to investigate the crucial role of platelets in thrombo-inflammation are warranted.

Is antiviral treatment at the acute phase of COVID-19 effective for decreasing the risk of long-COVID? A systematic review.

PURPOSE: Preliminary evidence suggests a potential effect of antiviral medication used during the acute COVID-19 phase for preventing long-COVID. This review investigates if having received pharmacological treatment during acute SARS-CoV-2 infection may reduce the risk of long-COVID. METHODS: MEDLINE, CINAHL, PubMed, EMBASE, Web of Science databases, as well as medRxiv/bioRxiv preprint servers were searched up to July 15th, 2023. Articles comparing the presence of long-COVID symptoms between individuals who received or not a specific medication, particularly antivirals, during the acute phase of SARS-CoV-2 infection were included. Methodological quality was assessed using the Newcastle-Ottawa Scale or Cochrane's Risk of Bias (Rob) tool. RESULTS: From 517 studies identified, 6 peer-reviewed studies and one preprint met all inclusion criteria. The sample included 2683 (n = 4) hospitalized COVID-19 survivors and 307,409 (n = 3) non-hospitalized patients. The methodological quality was high in 71% of studies (n = 5/7). Two studies investigating the effects of Nirmaltrevir/Ritonavir and three studies the effect of Remdesivir reported conflicting results on effectiveness for preventing long-COVID. Three studies investigating the effects of other medication such as Dexamethasone (n = 2) or Metformin (n = 1) found positive results of these medications for preventing long-COVID. CONCLUSION: Available evidence about the effect of medication treatment with antivirals during acute COVID-19 and reduced risk of developing long-COVID is conflicting. Heterogeneous evidence suggests that Remdesivir or Nirmaltrevir/Ritonavir could have a potential protective effect for long-COVID. A limited number of studies demonstrated a potential benefit of other medications such as Dexamethasone or Metformin, but more studies are needed.

New Twist on the Light-Switch Effect: Controlling the Fate of Excited States with pH in a 4-Hydroxy-thiazol-extended Ruthenium(II) Dppz Complex.

We present a pH-dependent study of the excited state dynamics of a novel Ru complex bearing a 4-hydroxy thiazol-substituted dppz (dipyridophenazine) ligand (RuTzOH) and its deprotonated form (RuTzO-). We combine steady-state and time-resolved absorption and emission spectroscopy with electrochemical investigations to characterize the excited state relaxation, which upon photoexcitation at 400 nm is determined by a multitude of initially populated MLCT states for both complexes. Subsequently, for RuTzOH, two long-lived excited states are populated, leading to dual emission from the complexes, a feature that vanishes upon deprotonation. Upon deprotonation, the electron density on the dppz moiety increases significantly, leading to rapid energy populating ligand-centered states and thus deactivating the initially excited MLCT states.

Thymoma metastatic to the epidural thoracic spine.

Background: Thymomas rarely metastasize to the spine. Here, we present a 69-year-old female diagnosed with stage IV thymoma, which subsequently developed a symptomatic epidural thoracic spinal lesion causing thoracic myelopathy. Case Description: The patient initially presented with paraspinal rib pain, lower extremity weakness, and gait imbalance. The magnetic resonance revealed a T10 vertebral body lesion with epidural extension causing severe spinal cord compression. A T9-T10 hemilaminotomy for tumor resection was performed; this was followed by adjuvant chemotherapy and radiation. Gross total resection was achieved, and the final pathology was metastatic thymoma. Postoperatively, the patient significantly improved. Conclusion: Metastatic thymomas to the thoracic spine are rare. For those presenting with epidural lesions causing myelopathy, surgical resection is beneficial and may be accompanied by adjunctive radiation and chemotherapy.

Infusion reactions to adeno-associated virus (AAV)-based gene therapy: Mechanisms, diagnostics, treatment and review of the literature.

The use of adeno-associated virus (AAV) vectors in gene therapy has demonstrated great potential in treating genetic disorders. However, infusion-associated reactions (IARs) pose a significant challenge to the safety and efficacy of AAV-based gene therapy. This review provides a comprehensive summary of the current understanding of IARs to AAV therapy, including their underlying mechanisms, clinical presentation, and treatment options. Toll-like receptor activation and subsequent production of pro-inflammatory cytokines are associated with IARs, stimulating neutralizing antibodies (Nabs) and T-cell responses that interfere with gene therapy. Risk factors for IARs include high titers of pre-existing Nabs, previous exposure to AAV, and specific comorbidities. Clinical presentation ranges from mild flu-like symptoms to severe anaphylaxis and can occur during or after AAV administration. There are no established guidelines for pre- and postadministration tests for AAV therapies, and routine laboratory requests are not standardized. Treatment options include corticosteroids, plasmapheresis, and supportive medications such as antihistamines and acetaminophen, but there is no consensus on the route of administration, dosage, and duration. This review highlights the inadequacy of current treatment regimens for IARs and the need for further research to improve the safety and efficacy of AAV-based gene therapy.

Outcomes of Extracorporeal Life Support in Children with Meningococcal Septicemia: A Retrospective Cohort Study.

Meningococcal disease is associated with high mortality despite aggressive antibiotic therapy and intensive care support. Patients may develop refractory hypotension and acute respiratory distress syndrome in which extracorporeal membrane oxygenation (ECMO) could serve as a life-saving rescue therapy. However, there is limited data regarding the outcomes of ECMO support in the setting of meningococcal disease. This retrospective analysis of prospectively collected data from Extracorporeal Life Support Organization registry (1989-2019) enrolled children (29 days-18 years old) with Neisseria meningitidis infection receiving ECMO for any support type and mode. A total of 122 patients underwent a single course of ECMO support, equating to 122 ECMO runs. The overall survival-to-discharge rate was 46.7%. Patients receiving pulmonary venovenous (VV) ECMO had the highest survival-to-discharge of 85.7%, while those receiving venoarterial (VA) ECMO for pulmonary indications had a survival of 32.4%. Patients receiving VA ECMO support for cardiac indications had a survival-to-discharge rate of 60.9%. Those needing extracorporeal cardiopulmonary resuscitation (ECPR) had a poor survival (14.3%). Hemorrhagic complications were common, occurring in 43.4% of patients, but not found to be associated with mortality (complication was present in 47.7% of deceased and 38.6% of survivors, p = 0.31). Multivariable logistic regression analysis revealed that neurologic complications were associated with increased odds of mortality (odds ratio: 44.11; 95% confidence interval: 4.95-393.08). ECMO can be utilized as rescue therapy in children with refractory cardiopulmonary failure in setting of meningococcemia. Patients who require pulmonary VV or cardiac ECMO have the best ECMO outcomes. However, the use of ECMO in those suffering cardiac arrest (ECPR) should be undertaken with caution.

Giant primary intracranial multi-fossa leiomyosarcoma involving the frontal sinus, ethmoid air cells, anterior fossa, middle fossa, and intraventricular space: A case report and literature review.

Background: Leiomyosarcomas (LMSs) is a type of sarcoma that arises from smooth muscle and generally presents in the abdomen. Although intracranial LMS has been identified before, most reported presentations have been in immunocompromised patients. Here, we present an intracranial LMS in an immunocompetent patient. Case Description: A 22-year-old male with a history of an atypical pineal parenchymal tumor of intermediate differentiation resected by suboccipital craniotomy at the age of 12 followed by adjuvant radiation therapy, presented with 3 weeks of decreased appetite, weight loss, and lethargy. He subsequently underwent transbasal approach skull base tumor resection. Histologic examination of the mass along with the patient's history of radiation was supportive of a low-grade, radiation-induced LMS arising from the anterior fossa of the skull or meninges and extends to the frontal sinus and ethmoid air cells. Conclusion: Primary intracranial LMS is an extremely rare diagnosis and presenting symptoms vary with the location and size of the tumor. Due to the poor specificity of clinical symptoms, diagnosis is often based on histology. The most common treatment is surgical resection. Adjuvant chemotherapy with various agents has been found to be somewhat effective outside the central nervous system. When LMS does occur, a history of immunocompromised state or previous radiation exposure is often present. Pathological confirmation is required for an appropriate diagnosis.

Percutaneous high cervical spinal cord stimulation for refractory trigeminal neuralgia.

Background: Trigeminal neuralgia (TN) is a debilitating pain that affects the dermatomes associated with the trigeminal nerve (V1, V2, and V3). Unfortunately, many medical treatments and surgical procedures fail to sufficiently modulate the pain associated with this condition. Case Description: This study presents two extreme cases of refractory TN (RTN) that progressed to atypical facial pain and describes successful mitigation of the neuralgia of said cases by percutaneous implantation of upper cervical spinal cord stimulation (SCS). The SCS was designed to target the descending spinal trigeminal tract. Conclusion: Together, these cases collaborate with the limited literature and further delineate the use and potential advantages of SCS in the treatment of RTN.

New Zealand patients have a higher melanoma burden in sentinel nodes and completion lymphadenectomy than patients in MSLT-II.

New Zealand has the highest rate of melanoma-related mortality in the world. Access to immunotherapy and radiology is limited and surgical treatment of regional disease remains important. A recent pilot study of a single health district observed a higher nodal melanoma burden than was reported in the second Multicentre Selective Lymphadenectomy Trial (MSLT-II). In this study, a series of regional censuses were undertaken covering the 10 years immediately prior to the publication of MSLT-II. The study population was seven District Health Boards covering 62.2% of the population of New Zealand across a 10-year period preceding MSLT-II. The primary outcomes measured were the size of sentinel lymph node metastases and non-sentinel node (NSN) positivity on completion lymph node dissection (CLND) for patients with a positive sentinel lymph node biopsy (SLNB). In the 2323 SLNB identified, the mean sentinel lymph node metastatic deposit size was larger compared to MSLT-II (2.55 vs. 1.07/1.11 mm). A greater proportion of New Zealand patients (44.2%) had metastatic deposits larger than 1 mm compared to MSLT-II (33.2/34.5%) and the rate of non-sentinel node involvement on CLND was also higher (22.2% vs. 11.5%). These findings indicate that New Zealand is a high-risk population for nodal melanoma metastases. Due to these differences, the conclusions of MSLT-II may not be able to be applied to melanoma patients in the 7 regions studied in New Zealand.

Discontinuity of marginal artery at splenic flexure and rectosigmoid junction: A systematic review and meta-analysis.

AIM: The aim of this study was to provide comprehensive evidence-based assessment of the discontinuity of the marginal artery at the splenic flexure (SF) and the rectosigmoid junction (RSJ). METHOD: A systematic review was conducted of literature published to 26 December 2022 in the electronic databases PubMed, SCOPUS and Web of Science to identify studies eligible for inclusion. Data were extracted and pooled into a meta-analysis using the Metafor package in R. The primary outcomes were the pooled PPEs of the marginal artery at the SF and the RSJ. The secondary outcome was the size of vascular anastomoses. RESULTS: A total of 21 studies (n = 2,864 patients) were included. The marginal artery was present at the splenic flexure in 82% (95% CI: 62-95) of patients. Approximately 81% (95% CI: 63-94%) of patients had a large macroscopic anastomosis, while the remainder (19%) had small bridging ramifications forming the vessel. The marginal artery was present at the RSJ in 82% (95% CI: 70-91%) of patients. CONCLUSION: The marginal artery may be absent at the SF and the RSJ in up to 18% of individuals, which may confer a higher risk of ischaemic colitis. As a result of high interstudy heterogeneity noted in our analysis, further well-powered studies to clarify the prevalence of the marginal artery at the SF and the RSJ, as well as its relationship with other complementary colonic collaterals (intermediate and central mesenteric), are warranted.

Effects of Different Types of Recombinant SARS-CoV-2 Spike Protein on Circulating Monocytes' Structure.

This study investigated the biological effects on circulating monocytes after challenge with SARS-CoV-2 recombinant spike protein. Whole blood collected from seven ostensibly healthy healthcare workers was incubated for 15 min with 2 and 20 ng/mL final concentration of recombinant spike protein of Ancestral, Alpha, Delta, and Omicron variants. Samples were analyzed with Sysmex XN and DI-60 analyzers. Cellular complexity (i.e., the presence of granules, vacuoles and other cytoplasmic inclusions) increased in all samples challenged with the recombinant spike protein of the Ancestral, Alpha, and Delta variants, but not in those containing Omicron. The cellular content of nucleic acids was constantly decreased in most samples, achieving statistical significance in those containing 20 ng/mL of Alpha and Delta recombinant spike proteins. The heterogeneity of monocyte volumes significantly increased in all samples, achieving statistical significance in those containing 20 ng/mL of recombinant spike protein of the Ancestral, Alpha and Delta variants. The monocyte morphological abnormalities after spike protein challenge included dysmorphia, granulation, intense vacuolization, platelet phagocytosis, development of aberrant nuclei, and cytoplasmic extrusions. The SARS-CoV-2 spike protein triggers important monocyte morphological abnormalities, more evident in cells challenged with recombinant spike protein of the more clinically severe Alpha and Delta variants.

Characteristics of Phase IV Clinical Trials in Oncology: An Analysis Using the ClinicalTrials.gov Registry Data.

The present study analyzed the characteristics of phase IV clinical trials in oncology using data from the ClinicalTrials.gov registry. The included trials were conducted between January 2013 and December 2022 and were examined for key characteristics, including outcome measures, interventions, sample sizes, and study design, different cancer types, and geographic regions. The analysis included 368 phase IV oncology studies. An amount of 50% of these studies examined both safety and efficacy, while 43.5% only reported efficacy outcome measures, and 6.5% only described safety outcome measures. Only 16.9% of studies were powered to detect adverse events with a frequency of 1 in 100. Targeted therapies accounted for the majority of included studies (53.5%), with breast (32.91%) and hematological cancers (25.82%) being the most frequently investigated malignancies. Most phase IV oncology studies lacked sufficient power to detect rare adverse events due to their small sample sizes and instead focused on effectiveness. To ensure that there is no gap in drug safety data collection and detection of rare adverse events due to limited phase IV clinical trials, there is a significant need for additional education and participation by both health care providers and patients in spontaneous reporting processes.