Dark urine as the initial manifestation of COVID-19: a case report

Background Rhabdomyolysis is defined as a syndrome consisting of muscle necrosis and the release of intracellular muscle components into the bloodstream. Although rhabdomyolysis has been previously reported as an initial presentation or late complication of COVID-19, the data on it is still limited, and currently, there is no single case of COVID-19 in the literature that describes creatine kinase levels of more than 30,000 IU/L. Case presentation A 50-year-old African–American male presented to the hospital with decreased urine output, dark urine color, and constipation for the past couple of days. He was found to have acute kidney injury, liver injury, and creatinine kinase of 359,910 IU/L, for which aggressive intravenous fluid therapy was given. Infectious workup resulted in positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction. Two days after admission, the patient became symptomatic from a coronavirus disease 2019: he developed fever and hypoxia, and was placed on supplemental oxygen and started on a 10-day course of dexamethasone. The patient responded well to the treatment and supportive care for coronavirus disease 2019 and was successfully discharged. Conclusion Clinicians should be cognizant of atypical coronavirus disease 2019 presentations. The spectrum of damage of coronavirus disease 2019 is still an evolving topic, and more research is required to reveal the exact mechanisms by which severe acute respiratory syndrome coronavirus 2 leads to rhabdomyolysis.

NICOLAU SYNDROME IN A CHILD FOLLOWING IV CLINDAMYCIN INJECTION-DECODING THE PURPLE PUZZLER

Nicolau syndrome is a rare complication of intramuscular injections caused by various drugs that present with intense pain and induration at the injection site. It is characterized by local aseptic skin necrosis and rarely, muscle necrosis on the injection site. It has rarely been reported to occur after intramuscular injections of anti-inammatory drugs, corticosteroids, local anesthetics, penicillin and interferon. Our literature review revealed no cases of Nicolau syndrome following intravenous (IV) clindamycin injections. Herein, we report a case of Nicolau syndrome that occurred after IV clindamycin injection in the left forearm of a 1.5-year child, that was notable because of the uniqueness of the syndrome coupled with the fact that it has not previously been reported after intravenous clindamycin injection.

SP5.2.5 A 4-year single-centre cohort study assessing outcomes in vascular surgery patients undergoing calf fasciotomies

Aims Acute compartment syndrome (ACS) is a surgical emergency. Delayed diagnosis and fasciotomy can result in irreversible muscle necrosis causing permanent disability and major amputation. This study compared patient outcomes following calf fasciotomies to prevent ACS (prophylactic) versus treat ACS (therapeutic) and early (within 6 hours of ACS diagnosis) versus delayed fasciotomies (beyond 6 hours) at a single vascular centre. Methods All patients undergoing calf fasciotomies between 1st January 2017 and 31st December 2020 were identified from a prospectively collected departmental database. Caldecott-approved data collection was conducted. The primary outcomes were wound infection, foot drop, muscle debridement, split-skin graft (SSG) requirement, vacuum dressing, 30-day amputation and death rates. Statistical analysis was performed using Fisher’s exact test. Results 73 patients (51 men, 22 women; median age 67, IQR 56-75 years) underwent calf fasciotomies (44 therapeutic and 29 prophylactic) mainly following acute thromboembolic ischaemia. Higher complication rates occurred among delayed (15) versus early (29) fasciotomy patients: wound infection (13.3% vs 3.4%), foot drop (20.0% vs 3.4%), muscle debridement (40.0% vs 24.1%), loss of anterior compartment (13.3%, 3.4%) need for SSG (29.5% vs 17.2%), vacuum dressing (46.7% vs 20.7%) and 30-day amputation rate (20.0% vs 13.8%) but lower 30-day death rate 13.3% vs 17.2%). None of these results were statistically significant. 34.1% of delayed fasciotomies were due to awaiting emergency theatre availability. Conclusion ACS patients undergoing calf fasciotomies are at high risk of complications including amputation and death. Ongoing education on mortality risk and early communication with emergency theatres are critical in their management.

Hematopoietic Prostaglandin D Synthase Inhibitor PK007 Decreases Muscle Necrosis in DMD mdx Model Mice

Duchenne muscular dystrophy (DMD) is characterized by progressive muscle weakness and wasting due to the lack of dystrophin protein. The acute phase of DMD is characterized by muscle necrosis and increased levels of the pro-inflammatory mediator, prostaglandin D2 (PGD2). Inhibiting the production of PGD2 by inhibiting hematopoietic prostaglandin D synthase (HPGDS) may alleviate inflammation and decrease muscle necrosis. We tested our novel HPGDS inhibitor, PK007, in the mdx mouse model of DMD. Our results show that hindlimb grip strength was two-fold greater in the PK007-treated mdx group, compared to untreated mdx mice, and displayed similar muscle strength to strain control mice (C57BL/10ScSn). Histological analyses showed a decreased percentage of regenerating muscle fibers (~20% less) in tibialis anterior (TA) and gastrocnemius muscles and reduced fibrosis in the TA muscle in PK007-treated mice. Lastly, we confirmed that the DMD blood biomarker, muscle creatine kinase activity, was also reduced by ~50% in PK007-treated mdx mice. We conclude that our HPGDS inhibitor, PK007, has effectively reduced muscle inflammation and fibrosis in a DMD mdx mouse model.

1001 Atraumatic Bilateral Compartment Syndrome; A Case Report

Introduction We present a rare case of lower leg atraumatic bilateral compartment syndrome (ABCS). To date there have only been three similar cases reported where no cause was identified. Case Study A 33-year-old male presented 12 hours following sudden onset lower leg pain. There was no history of trauma, drug, or alcohol use. On assessment he was in significant pain, not relieved by analgesia, and had clinically tense anterior compartments bilaterally. Both feet were held in fixed dorsiflexion. Creatinine kinase (CK) was 35,166 on admission. X-rays of both legs were normal. He was immediately taken to theatre for bilateral four compartment fasciotomies which revealed significant swelling in the anterior and lateral compartments with patchy pre-necrosis. Post-operatively he deteriorated, required intubation, and was admitted to ITU for acute haemofiltration to treat acute kidney injury secondary to rhabdomyolysis. Multiple operations were required for debridement, resulting in exposed tendons. Closure of the medial wounds was achieved primarily as an inpatient and he was discharged with bilateral lateral VAC dressings in situ. Lateral wounds were closed with Biodegradable Temporising Matrix followed by split skin grafting. In his second admission he suffered a pulmonary embolism. Literature Review and Discussion 20 case of ABCS have been reported, largely attributable to drugs, alcohol, or leg position. Most cases had an element of diagnostic delay. In addition to compartment pressure monitoring, testing CK can demonstrate muscle necrosis and supports the decision to proceed to surgery.

Suspected Compartment Syndrome and Rhabdomyolysis after “Pseudoephedrine” Use: A Case Report

Acute compartment syndrome and rhabdomyolysis are two life threatening diagnoses that cannot be missed in the emergency room. The increased pressure in the closed compartments of extremities can eventually lead to loss of peripheral pulses, decreased tissue perfusion, and ultimately muscle necrosis. This breakdown of muscle byproducts will ultimately lead to kidney damage and rhabdomyolysis. Although the most common cause of compartment syndromes are secondary orthopedic causes such as lower extremity fractures there are known documented toxicological causes. (1,2) Pseudoephedrine, a sympathomimetic amine, is commonly used in the treatment of nasal congestion. Its primary mechanism directly acts on the adrenergic receptor system which stimulates release of stored norepinephrine from neurons. Its alpha-adrenergic effect is believed to be the cause of vasoconstriction in the body (3) Clinically, intoxication from sympathomimetic drugs have produced toxidromes with prominent features such as tachycardia, hypertension, hyperthermia, agitation, and delirium. However, it is incredibly rare to see an association with pseudoephedrine overdose and rhabdomyolysis and compartment syndrome. There are documented cases where sympathomimetic drugs have been associated with compartment syndrome (2,4,5) This case of a 29-year-old male with suspected pseudoephedrine abuse highlights the need for consideration of rhabdomyolysis and compartment syndrome being a possible complication from pseudoephedrine overdose.

Characterization of Coxsackievirus A6 Strains Isolated From Children With Hand, Foot, and Mouth Disease

Coxsackievirus A6 (CVA6) is a key pathogen causing hand, foot and mouth disease (HFMD). However, there are currently no specific antiviral drugs or vaccines for treating infections caused by CVA6. In this study, human rhabdomyosarcoma (RD), African green monkey kidney (Vero), and human embryonic lung diploid fibroblast (KMB17) cells were used to isolate CVA6 from 327 anal swab and fecal samples obtained during HFMD monitoring between 2009 and 2017. The VP1 genes of the isolates were sequenced and genotyped, and the biological characteristics of the representative CVA6 strains were analyzed. A total of 37 CVA6 strains of the D3 gene subtypes were isolated from RD cells, all of which belonged to the epidemic strains in mainland China. Using the adaptive culture method, 10 KMB17 cell-adapted strains were obtained; however, no Vero cell-adapted strains were acquired. Among the KMB17 cell-adapted strains, only KYN-A1205 caused disease or partial death in suckling mice, and its virulence was stronger than its RD cell-adapted strain. The pathogenic KYN-A1205 strain caused strong tropism to the muscle tissue and led to pathological changes, including muscle necrosis and nuclear fragmentation in the forelimb and hindlimb. Sequence analysis demonstrated that the KYN-A1205 strain exhibited multiple amino acid mutations after KMB17 cell adaptation. Moreover, it showed strong pathogenicity, good immunogenicity and genetic stability, and could be used as an experimental CVA6 vaccine candidate.

Progressive increases in creatine kinase activity in an anorexic cat with necrotising myopathy

Case summary A 5-year-old castrated male domestic shorthair cat with weight loss and reduced appetite was evaluated for increased and progressively rising creatine kinase (CK) activity. The cat had recently been diagnosed with hepatic lipidosis. Muscle biopsy and histopathology revealed mild myonecrosis and phagocytosis without obvious inflammatory cell infiltrates. Resolution of necrotising myopathy was observed after a short course of anti-inflammatory prednisolone and nutritional supplementation. Relevance and novel information This is the first report of a necrotising myopathy in a cat associated with progressively increasing CK activity and decreased appetite. Anorexia in cats has been associated with increased CK activity, but an underlying cause of this CK elevation has only been postulated. Here we document muscle necrosis and muscle stiffness in a cat with anorexia.

Mechanics of dystrophin deficient skeletal muscles in very young mice and effects of age

The MDX mouse is an animal model of Duchenne muscular dystrophy, a human disease marked by an absence of the cytoskeletal protein, dystrophin. We hypothesized that (1) dystrophin serves a complex mechanical role in skeletal muscles by contributing to passive compliance, viscoelastic properties, and contractile force production and (2) age is a modulator of passive mechanics of skeletal muscles of the MDX mouse. Using an in vitro biaxial mechanical testing apparatus, we measured passive length-tension relationships in the muscle fiber direction as well as transverse to the fibers, viscoelastic stress-relaxation curves, and isometric contractile properties. To avoid confounding secondary effects of muscle necrosis, inflammation, and fibrosis, we used very young 3-week-old mice whose muscles reflected the pre-fibrotic and pre-necrotic state. Compared to controls, 1) muscle extensibility and compliance were greater in both along fiber direction and transverse to fiber direction in MDX mice and 2) the relaxed elastic modulus was greater in dystrophin-deficient diaphragms. Furthermore, isometric contractile muscle stress was reduced in the presence and absence of transverse fiber passive stress. We also examined the effect of age on the diaphragm length-tension relationships and found that diaphragm muscles from 9-months old MDX mice were significantly less compliant and less extensible than those of muscles from very young MDX mice. Our data suggest that the age of the MDX mouse is a determinant of the passive mechanics of the diaphragm; in the pre-fibrotic/pre-necrotic stage, muscle extensibility and compliance, as well as viscoelasticity, and muscle contractility are altered by loss of dystrophin.

RhoA/ROCK2 signalling is enhanced by PDGF-AA in fibro-adipogenic progenitor cells in DMD

ABSTRACTThe lack of dystrophin expression in Duchenne muscular dystrophy (DMD) leads to muscle necrosis and replacement of muscle tissue by fibro-adipose tissue. Although the role of some growth factors in the process of fibrogenesis has been previously studied, the pathways that are activated by PDGF-AA in muscular dystrophies have not been described so far. Herein we report the effects of PDGF-AA on the fibrotic process in muscular dystrophies by performing a quantitative proteomic study in DMD isolated fibro-adipogenic precursor cells (FAPs) treated with PDGF-AA. In vitro studies showed that RhoA/ROCK2 pathway is activated by PDGF-AA and induces the activation of FAPs. The inhibition of RhoA/ROCK signalling pathway by C3-exoenzyme or fasudil attenuated the effects of PDGF-AA. The blocking effects of RhoA/ROCK pathway were analysed in the dba/2J-mdx murine model with fasudil. Grip strength test showed an improvement in the muscle function and histological studies demonstrated reduction of the fibrotic area. Our results suggest that blockade of RhoA/ROCK could attenuate the activation of FAPs and could be considered a potential therapeutic approach for muscular dystrophies.