Enhancing capillary blood collection: The influence of nicotinic acid and nonivamide.

BACKGROUND: Nicotinic acid and nonivamide are often applied topically during capillary blood collection to induce vasodilation. These molecules may have an influence on immune effector cell activity in nearby tissues. This study investigates whether the induction of flushing by nicotinic acid and nonivamide causes an inflammatory response that influences the composition of immune cells present in a capillary blood sample. METHODS: Females aged between 18 and 30 years old provided capillary blood samples. Experimental samples were taken from an earlobe treated with nicotinic acid and nonivamide with controls obtained from the untreated earlobe. Immunophenotypic analyses were conducted using polychromatic flow cytometry to determine whether any changes occurred in leucocyte subpopulations (CD3, CD4, CD8, CD19, CD56, and CD14) and granulocytic functional-related surface antigen markers (CD11b, CD18, CD16b, and CD66b). RESULTS: No significant differences were observed between experimental and control samples in the mean percent of parent for the lymphocyte, monocyte, or granulocyte subpopulations, or in the median fluorescence intensity of particular surface markers expressed on these leucocytes. CONCLUSION: The topical application of nicotinic acid and nonivamide is a possible method to improve capillary blood collection for immunological assessments. The use of these agents may increase the safety and compliance of patients who suffer from needle phobia or are unable to provide venous blood samples.

Loss of catalytically inactive lipid phosphatase myotubularin-related protein 12 impairs myotubularin stability and promotes centronuclear myopathy in zebrafish.

X-linked myotubular myopathy (XLMTM) is a congenital disorder caused by mutations of the myotubularin gene, MTM1. Myotubularin belongs to a large family of conserved lipid phosphatases that include both catalytically active and inactive myotubularin-related proteins (i.e., "MTMRs"). Biochemically, catalytically inactive MTMRs have been shown to form heteroligomers with active members within the myotubularin family through protein-protein interactions. However, the pathophysiological significance of catalytically inactive MTMRs remains unknown in muscle. By in vitro as well as in vivo studies, we have identified that catalytically inactive myotubularin-related protein 12 (MTMR12) binds to myotubularin in skeletal muscle. Knockdown of the mtmr12 gene in zebrafish resulted in skeletal muscle defects and impaired motor function. Analysis of mtmr12 morphant fish showed pathological changes with central nucleation, disorganized Triads, myofiber hypotrophy and whorled membrane structures similar to those seen in X-linked myotubular myopathy. Biochemical studies showed that deficiency of MTMR12 results in reduced levels of myotubularin protein in zebrafish and mammalian C2C12 cells. Loss of myotubularin also resulted in reduction of MTMR12 protein in C2C12 cells, mice and humans. Moreover, XLMTM mutations within the myotubularin interaction domain disrupted binding to MTMR12 in cell culture. Analysis of human XLMTM patient myotubes showed that mutations that disrupt the interaction between myotubularin and MTMR12 proteins result in reduction of both myotubularin and MTMR12. These studies strongly support the concept that interactions between myotubularin and MTMR12 are required for the stability of their functional protein complex in normal skeletal muscles. This work highlights an important physiological function of catalytically inactive phosphatases in the pathophysiology of myotubular myopathy and suggests a novel therapeutic approach through identification of drugs that could stabilize the myotubularin-MTMR12 complex and hence ameliorate this disorder.

QT Prolongation After His Bundle Pacing: What Is the Mechanism?

An 82-year-old woman with nonischemic cardiomyopathy underwent cardiac resynchronization therapy by the use of His bundle pacing. After the procedure, the patient had repolarization abnormality with severely prolonged QTc and anterior inferior T-wave inversions, likely resulting from memory T waves associated with the correction of long-standing left bundle branch block. These changes could be potentially arrhythmogenic. (Level of Difficulty: Intermediate.).

Shoulder injury related to vaccine administration (SIRVA) after COVID-19 vaccination.

OBJECTIVE: The global fight against COVID-19 has required mass vaccination clinics as well as mass recruitment of personnel, including many who may not regularly administer intramuscular deltoid immunizations, potentially increasing the incidence of improper intramuscular injection. Shoulder injury related to vaccine administration (SIRVA) is a well-described, preventable injury resulting from improper injection into anatomic structures adjacent to the deltoid muscle leading to mechanical and chemical trauma augmented by an inflammatory immune response to the vaccine and/or adjuvants. SIRVA is best described in the setting of influenza vaccination, and little is known about it as it pertains to COVID-19 vaccination. This study aims to describe SIRVA in the current pandemic, increase clinician awareness, and offer considerations for prevention. METHODS: To identify clinical characteristics of patients with post-COVID-19-vaccination shoulder injuries, we performed a systematic review of the cases of vaccination-related shoulder injuries reported in the literature and conducted a review of the public Vaccine Adverse Event Reporting System (VAERS). RESULTS: We identified 305 cases of SIRVA in the VAERS database and 28 cases of SIRVA in the setting of COVID-19 vaccination from the literature (n = 333). Patients had a mean age of 51.8 years and a median of 51.5 (range: 19-90) years. Of these, 76.3% were female and 23.7% male. Most patients sought medical evaluation with 54 of the 305 VAERS cases reporting utilizing emergency services. Of patients with imaging-confirmed SIRVA (n = 95), the most common diagnoses were adhesive capsulitis and bursitis, and the most common symptoms were pain (97.7%) and limited range of motion (68.1%). Most patients reported requiring treatment with the majority receiving physical therapy (56.3%), followed by cortisone injection (34.4%). Other modalities used were non-steroidal anti-inflammatory drugs, oral steroids, and surgery. Only 5 patients from this group reported recovery while 60 stated they had not yet recovered. Of those, 23.3% reported disability. CONCLUSION: SIRVA should be regarded as an under-reported, significant cause of post-vaccination morbidity. In the setting of COVID-19 mass vaccination, clinicians must be aware of signs and symptoms of SIRVA as well as appropriate diagnostic modalities and treatment options. Additionally, standardization and proper education regarding injection technique and appropriate needle length is imperative to reducing harm.

A Case of Leishmaniasis Infantum Kala-Azar in an Immunocompetent 49-Year-Old Man.

An immunocompetent 45-year-old Cuban-American man presented with worsening knee pain and swelling despite antibiotic therapy. On physical examination, the patient was ill-appearing, cachectic, with a protuberant abdomen and massive splenomegaly. In addition, he had a 10 cm area of peripheral hyperemia with central necrosis in the medial left knee that was non-tender and non-fluctuant. Initial lab work demonstrated pancytopenia, hyponatremia, hypoalbuminemia, and anemia of chronic inflammation. Peripheral smear showed microcytic, hypochromic red blood cells with mild anisopoikilocytosis. and leukopenia with slight left shift and metamyelocytes. Bone marrow biopsy demonstrated amastigotes and kinetoplasts within white blood cells and extracellular space consistent with leishmaniasis. Centers for Disease Control and Prevention (CDC) testing with PCR returned positive for Leishmaniasis infantum. The patient received two courses of amphotericin B lipid complex (ABLC) with a 28-day course of miltefosine, which resulted in clinical improvement. This case illustrates the unique pathology that can affect immigrants and highlights the need to increase health provider awareness of foreign pathologies in areas with large migrant populations.

Bleomycin-Induced Lung Injury After Intravenous Iron Administration.

Bleomycin is an antibiotic that is often used as a chemotherapeutic agent due to its antitumor activities against a variety of malignancies. A feared and often fatal side effect of this drug is a pulmonary injury causing inflammation that can progress to pulmonary fibrosis. Bleomycin damages lung endothelial cells by the production of free radicals that can only occur when it is bound to certain metals in the body. It forms a complex with iron and once activated by iron reduction, it destroys deoxyribonucleic acid (DNA). Therefore, it is suggested that the availability of iron in the body may play a role in the pathogenesis of bleomycin toxicity although no related cases have been documented. This is a case of a 75-year-old female with no prior history of pulmonary disease who was diagnosed with Hodgkin's lymphoma and received 12 doses of bleomycin over the course of six cycles of chemotherapy. She then presented to the hospital with respiratory failure five months after her completion of treatment. Interestingly, one month prior to presentation, she was given two intravenous iron infusions of ferumoxytol five days apart for the treatment of iron deficiency anemia. Within a week of receiving the iron, she developed dyspnea with a nonproductive cough. About a month after she developed these symptoms, she presented to the hospital and was found to be hypoxic with any activity and was subsequently placed on oxygen via nasal cannula. Her lung imaging showed new reticulonodular and patchy infiltrates bilaterally concerning for pneumonitis and her physical examination was significant for black discoloration of her fingertips and toes along with expiratory rhonchi heard throughout her lungs. During the hospitalization, her oxygen requirements increased, and the patient ended up in the intensive care unit on bilevel positive airway pressure. Her lung imaging, rapid progression, and skin findings made the clinical diagnosis of bleomycin toxicity. Out of concern that the intravenous iron may have played a role in the toxicity, iron chelation was attempted. The patient was given two doses of deferoxamine over two consecutive days and her symptoms of dyspnea along with her oxygen requirements improved. Unfortunately, these positive effects only lasted a few days and the patient continued to decline and ultimately passed away. This case raises many questions regarding iron's role in bleomycin toxicity, including if intravenous iron infusions may increase the risk of pulmonary injury from bleomycin. There are currently no guidelines or recommendations that suggest withholding iron supplementation in patients undergoing chemotherapy with bleomycin. There is also insufficient evidence to support the routine use of iron chelation in a patient that presents with bleomycin-induced lung injury. However, some studies suggest that iron chelation may play a role in preventing pulmonary toxicity. It may also lessen the severity of the toxicity or improve some of the related symptoms, thus warranting further research.

Portal and Mesenteric Vein Thrombosis Associated with Decompression Sickness in a 48-Year-Old Deep Sea Self-Contained Underwater Breathing Apparatus (SCUBA) Diver.

BACKGROUND Deep sea diving can cause decompression illness which comprises both decompression sickness and arterial gas embolism. Decompression sickness is a clinical diagnosis with symptoms including dizziness, joint pain, rash, and myalgias and is due to nitrogen bubbles that form in tissues during ascent. These gas bubbles can be clinically silent even in the absence of decompression sickness and can rarely predispose a patient to venous thrombus, for which the role of hyperbaric oxygen (HBO) is undefined. The following case describes a male diver who developed portal and mesenteric venous thrombosis secondary to silent nitrogen venous bubbles. CASE REPORT A 48-year-old man developed abdominal pain 1 day after diving to a maximum depth of 13.7 m, without clinical symptoms of decompression sickness after surfacing. He presented to the Emergency Department 10 days later, and magnetic resonance angiogram revealed a diagnosis of gas containing superior mesenteric and portal vein thrombus. Due to the lack of guidelines of HBO with the presence of a thrombus and timing since onset, HBO therapy was not pursued. Oral anticoagulation was initiated, and symptoms resolved. CONCLUSIONS This patient developed gastrointestinal illness 1 day after diving that was later found to be due to thrombosis. Other etiologies were ruled out, making silent nitrogen bubbles within the venous system the most likely etiology. Vascular thrombosis is a rare complication of diving and lacks guidelines for treatment. While HBO is a known treatment for decompression sickness, there are no clinical guidelines for diving-associated thrombi, representing an area for further research.

Subdural hematoma expansion in relation to measured mean and peak systolic blood pressure: A retrospective analysis.

Objective: Subdural hematomas (SDH) account for an estimated 5 to 25% of intracranial hemorrhages. Acute SDH occur secondary to rupture of the bridging veins leading to blood collecting within the dural space. Risk factors associated with SDH expansion are well documented, however, there are no established guidelines regarding blood pressure goals in the management of acute SDH. This study aims to retrospectively evaluate if uncontrolled blood pressure within the first 24 h of hospitalization in patients with acute SDH is linked to hematoma expansion as determined by serial CT imaging. Methods: A single center, retrospective study looked at 1,083 patients with acute SDH, predominantly above age 65. Of these, 469 patients met the inclusion criteria. Blood pressure was measured during the first 24 h of admission along with PT, INR, platelets, blood alcohol level, anticoagulation use and antiplatelet use. Follow-up CT performed within the first 24 h was compared to the initial CT to determine the presence of hematoma expansion. Mean systolic blood pressure (SBP), peak SBP, discharge disposition, length of stay and in hospital mortality were evaluated. Results: We found that patients with mean SBP <140 in the first 24 h of admission had a lower rate of hematoma expansion than those with SBP > 140. Patients with peak SBP > 200 had an increased frequency of hematoma expansion with the largest effect seen in patients with SBP > 220. Other risk factors did not contribute to hematoma expansion. Conclusions: These results suggest that blood pressure is an important factor to consider when treating patients with SDH with medical management. Blood pressure management should be considered in addition to serial neurological exams, repeat radiological imaging, seizure prophylaxis and reversal of anticoagulation.

A Case of Toxicity from Cannabidiol Gummy Ingestion.

A 56-year-old male with no known history of substance abuse and no known prior medical conditions presented via ambulance to the emergency department after being found by coworkers with bizarre behavior, vomiting, and slurred speech. He had legally purchased cannabidiol (CBD) gummies marketed for pain and anxiety relief at a gas station several hours prior. Vitals upon arrival were temperature 36.8 Celsius, heart rate (HR) 79, respiratory rate (RR) 12, blood pressure (BP) 113/60, and oxygen saturation (O2) of 84% on room air that improved upon arousal. Physical exam showed an obese man in no acute distress with a depressed level of consciousness but who awoke to painful stimuli. Neuro exam was significant for dysarthric, hypophonic speech. Labs were significant for a primary respiratory acidosis with concomitant mild lactic acid elevation, normal bicarbonate, and normal anion gap. A comprehensive urine toxicology screen including cannabis was negative. Vital signs three hours after presentation deteriorated, showing: HR 47, RR 8-12, BP 88/52, O2 78%. Electrocardiogram (EKG) revealed sinus bradycardia. The patient progressively became more obtunded and required constant stimuli in order to maintain a patent airway. Non-invasive positive pressure ventilation was not administered due to persistent emesis. The patient underwent supportive care with intravenous fluids, oxygen, anti-emetics, continuous stimulation, and close neurologic monitoring with full recovery by the following morning. Further, patient history revealed that he had consumed two packages of CBD gummies, totaling 370 mg total of CBD (serving size on the package was 30 mg). He felt the products were healthy and safe based on packaging and therefore did not believe they would have any adverse effects. CBD is one of many cannabinoids found in marijuana and marijuana-derived products. It is generally considered safe unlike its more psychoactive counterpart, tetrahydrocannabinol (THC), which has been linked to seizures, respiratory depression, and cardiovascular complications. CBD has surged in popularity recently, being marketed in oils, capsules, and candies as a health supplement, claiming to treat a wide variety of medical conditions such as glaucoma, pain, and even having beneficial effects on cancer prevention. Most currently available studies do not look at isolated CBD nor their synthetic equivalents, and purity is not guaranteed, thus leading to unforeseen side effects and toxicities. Moreover, these compounds do not show on traditional toxicology screens, posing a diagnostic dilemma for physicians. This case of respiratory depression and cardiovascular compromise in a relatively healthy man is just one example of the importance of considering synthetic CBD toxicity in the differential diagnosis, as there is little data available for recognizing and treating this condition.

Rare Complication of Pneumomediastinum and Pneumopericardium in a Patient with COVID-19 Pneumonia.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently discovered coronavirus which has caused a global outbreak of severe pneumonia with complications leading to hypoxic respiratory failure, acute respiratory distress syndrome (ARDS), cytokine storm, disseminated intravascular coagulation (DIC), and even gastrointestinal symptoms. While ground-glass opacity (GGO) is a typical radiographic finding associated most frequently with COVID-19 pneumonia, other less commonly noted atypical radiographic lung features include isolated lobar or segmental consolidation without GGO, discrete small nodules (centrilobular, "tree-in-bud"), lung cavitation, and smooth interlobular septal thickening with pleural effusion. Pneumomediastinum in COVID-19 patients has rarely been reported. A finding of pneumopericardium is unusual too. This report discusses the case of a young male with COVID-19 pneumonia who was found to have both these features on computed tomographic (CT) scans of his chest on presentation.