Evaluation of three different 99mTc-based mock-venom agents for lymphoscintigraphy studies in preclinical models of peripheral snakebite envenomation.

Snakebite envenomation is one of the major public health concerns across many countries; with the WHO designating it as a 'priority neglected tropical disease' and stressing for a need to develop novel therapeutic strategies to reduce death and disability rate by end of 2030. Since a major component of venom; the high molecular weight (HMw) toxins enter the bloodstream through lymphatic system, research is focusing on modulating the lymphatic flow rate after topical application of suitable drug candidates. Present study compared the suitability of three radiopharmaceutical agents, namely 99mTc-Sulfur colloid (SC), 99mTc-Phytate (Phy) and 99mTc-Human serum albumin (HSA), to be used as mock-venom agent in studying modulation in lymphatic flow rate in preclinical models of peripheral snakebite envenomation using lymphoscintigraphy studies. The study was performed in 72 Sprague Dawley rats; divided into six groups of 12 rats each. Control groups were given intradermal injection (1.29-1.48 MBq in 100 µl normal saline) of either 99mTc-Phy/ 99mTc-SC/ 99mTc-HSA into the tail as 'mock-venom'. In respective test groups, commercially available topical formulation (Anobliss® Cream) containing Nifedipine (Nif; 0.3% w/w) and Lidocaine (Lid; 1.5% w/w) was applied topically over the animals' lower body (tail and hind limbs) immediately within 20s of administering intradermal injection of the radiopharmaceutical. Any modulation in lymph transit time from periphery to systemic circulation was assessed using lymphoscintigraphy by taking dynamic gamma-scintigraphy images of 60s each till 1 h post-injection of the test radiopharmaceuticals. Significant difference in movement of the three radiopharmaceuticals was noted in terms of their lymphatic movement. 99mTc-Phy did not show significant travel through the lymphatics and the liver was faintly visualized in control as well as test intervention groups. In case of 99mTc-SC, significant changes in movement of the radiotracer after topical application of Nif/Lid in the test intervention groups were clearly noted in comparison to control (P < 0.05). Multiple numbers of lymph nodes (LNs) could be clearly visualized in control (5 ± 1 LNs) and test intervention groups (3 ± 1 LNs). Liver uptake was more prominent in control animals and it reduced significantly in test intervention groups. On the other hand, 99mTc-HSA showed lesser number of lymph nodes and higher accumulation in liver as compared to 99mTc-SC, suggesting very fast movement of this radiopharmaceutical. Results indicates that 99mTc-SC could be used as a suitable agent to mimic lymphatic transit behavior of HMw toxin components of snake venom and could therefore be used as a model in studying the effect of any test pharmacological intervention in modulating lymphatic transit rate. Additional advantage could be a significant reduction in the need for sacrificing large number of animals, particularly during initial screening phase of drug development cycle.

The Role of Point-of-Care Ultrasound (POCUS) in Envenomation by a Desert Viper.

BACKGROUND There are few reports of crotaline envenomation in Qatar, where clinically significant snakebite is infrequently encountered. This report presents a case that resulted in significant hematotoxicity. The report introduces the concept that there may be a role for point-of-care ultrasound (POCUS) as an Emergency Department (ED) bedside imaging tool in the early evaluation of crotaline snakebites. CASE REPORT A 53-year-old Bangladeshi male without any prior medical history or allergies presented to the ED at the Hamad General Hospital stating that a sand-colored snake with a large head had bitten him on an uncovered part of his distal right leg leading to moderate swelling. Baseline laboratory testing showed a single laboratory suggestion of hematotoxicity (borderline elevation in prothrombin time) and moderately elevated lactate, indicating the potential for localized tissue destruction. POCUS demonstration of subcutaneous edema extending proximal to the knee was interpreted as suggesting the bite may be sufficiently serious to warrant administration of antivenom as the swelling crosses a major joint. CONCLUSIONS The presentation of the current case provides useful information for crotaline envenomation evaluation and management in Qatar and surrounding Middle Eastern countries. The mainstays of therapy are early suspicion of hematotoxicity, close observation for soft tissue, and timely treatment with appropriate antivenom. The case presented also provides a suggestion that ED ultrasound (POCUS) may be of assistance in assessing and predicting subcutaneous edema extent in patients with crotaline envenomation.

Ultrasonography of sudden swollen tongue in a calf.

BACKGROUND: In cattle, the lingual diseases are primarily diagnosed postmortem by histopathological examination of the affected tongues obtained after the death or during necropsy. In humans, ultrasonography has been used to provide differential diagnoses, and for preoperative or intraoperative planning of glossectomy in various lingual diseases. This is a bovine clinical case report, in which ultrasonography for sudden swelling of the tongue, which was possibly caused by snake bite, was utilized as a preoperative indication to perform a glossectomy. CASE PRESENTATION: An eight-month-old female Japanese black calf presented with sudden swelling of the tongue with well-defined discoloration in the cranial region. A 10-MHz linear probe on a portable-type ultrasound machine (MyLabOne VET, Esaote Co., Genova, Italy) was applied to the ventral surface of the tongues in the affected case, and also in five healthy calves under sedation to observe normal tongues. Ultrasonography of the swollen tongue in this case revealed that the ventral lingual muscular layers were severely thickened compared with those of normal tongues. However, the muscle layers were regularly aligned with the echogenic muscular fibers. This resembled the lingual muscular architectures of normal tongues. Color-flow Doppler ultrasonography revealed that blood flow was weakened in the small peripheral vessels in the spaces between the lingual muscular structures, and was lacking in the deep lingual artery between the apex and base of the tongue. This finding was very different than that of normal tongues, which exhibited weakened or rich blood flows. Based on ultrasonographic findings, this case was treated with glossectomy. After recovery, the calf grew up normally with a normal appetite and rumination, and did not exhibit mouth pain behavior. Histopathologically, hemorrhagic necrotic changes, together with focal formation of fibrin thrombus in the lingual blood vessels in the affected tongue, were noted. CONCLUSIONS: To the best of our knowledge, the present report is the first description of lingual ultrasonography performed in cattle. In this case, ultrasonography enabled visualization of decreased vascularity, which might be associated with hemorrhage or formation of fibrin thrombus in the suddenly swollen tongue presented.

Use of infrared thermography in a case of systemic envenomation by the coral snake Micrurus frontalis (Duméril et al., 1854) in Sao Paulo, Brazil.

Infrared thermography is a technique that quantifies the thermal (infrared) radiation emitted by an object and produces a high-resolution, digital thermal image of it. Medically, this technique is used to visualize the body's surface temperature distribution in a non-invasive, safe, and convenient fashion. However, to the best of our knowledge, the use of infrared thermography for assessing the systemic effects of envenomation by coral snakes has not been reported. In this case report, we describe the use of this technique in the management of a case of snakebite in Sao Paulo, Brazil. A 51-year-old woman was bitten on the back of the right hand by Micrurus frontalis, a species of coral snake, 10 min prior to her arrival at the hospital. Infrared imaging performed at admission revealed elevated temperatures at the bite site and in the elbow, as well as the preservation of a normal distal thermal gradient in both hands. A few minutes later, the patient developed muscle weakness in the upper limbs and in the eyelids, and infrared imaging showed an alteration of the thermal gradient in both hands, reflecting the systemic action of the venom. Following these observations, the patient was treated with the specific antivenom and was discharged 48 h post admission. At the two-week follow-up, the thermal image obtained showed no anomalies, indicating the recovery of the patient. Hence, infrared thermography can be very useful in the early identification of systemic neurotoxicity in cases of Micrurus snake bites, facilitating the decision to prescribe the antivenom.

Pituitary dysfunction in survivors of Russell's viper snake bite envenomation: A prospective study.

PURPOSE: Endocrinal insufficiency caused by vasculotoxic snake envenomation is under-recognized and is mostly confined to a specific geographic area. We conducted a prospective study to determine the prevalence and pattern of pituitary-target gland insufficiencies caused by snake envenomation. MATERIALS AND METHODS: The hormonal evaluation of patients who had suffered from vasculotoxic snake envenomation was done at baseline and at 6 months of follow-up. Those patients with a documented hormonal insufficiency underwent magnetic resonance imaging (MRI) of the hypothalamo-pituitary area. The severity of envenomation was assessed by the acute physiology and chronic health evaluation II (APACHE-II) score, the sepsis-related organ failure assessment (SOFA) score, and the snake bite severity score (SBSS) for all patients. RESULTS: Seventy-six patients were seen during the study period, of which 60 were available for a repeat hormonal evaluation at 6 months, with the majority of patients belonging to the middle age group (mean age, 37.6 ± 14.9 years). The mean lag period at presentation was 32 ± 20 h. Thirty-five patients (46.1%) had coagulopathy, 20 patients (26.3%) had acute kidney injury (AKI), and 8 of 76 patients (10.5%) needed renal replacement therapy (RRT) in the form of hemodialysis. Six patients (out of 41 with vasculotoxic bites) developed chronic hypopituitarism, which was in continuation with the acute hypopituitarism that they developed. Growth hormone and glucocorticoid deficiencies were the most common endocrinopathies observed. The occurrence of hypopituitarism was observed only in patients with a vasculotoxic snake bite (due to Russell's viper); coagulopathy, renal insufficiency, or any of the scoring tools did not predict the occurrence of hypopituitarism. CONCLUSION: Acute asymptomatic and chronic symptomatic or asymptomatic hypopituitarism are important sequelae of viper bite in a small proportion of patients and can occur in the presence of normal pituitary imaging. Routine prospective pituitary hormone screening should be done in all patients within the first 6 months of envenomation by the vasculotoxic snakebite as chronic pituitary dysfunction can often occur in these patients.

Ultrasound findings in 42 patients with cytotoxic tissue damage following bites by South African snakes.

BACKGROUND: Snakebites that have cytotoxic venom can cause significant soft tissue swelling. Assessing the site and degree of swelling using ultrasound as a non-invasive technique would be an important tool for instituting appropriate treatment. METHODS: Forty-two patients who presented to a referral hospital in South Africa with cytotoxic swelling of the limbs from snakebite were assessed using ultrasound. The envenomed limb of each patient was scanned at the point of maximal swelling and compared with the unaffected limb at the same site. Data were presented as an expansion coefficient defined as the ratio of the thickness of tissue structure (subcutaneous tissue or muscle compartment) in the envenomed limb to that in the unaffected limb. A p value of 0.05 was regarded as significant, and 95% CIs were expressed throughout. RESULTS: The majority of bites were in the upper limb (27/42). Twenty-five patients were children less than 12 years. Tissue expansion was noted in both the subcutaneous and muscle compartments of the envenomed limbs. The site of swelling was predominantly in the subcutaneous tissues, while swelling in muscle compartment was limited (the mean expansion coefficient for subcutaneous tissues was 2.0 (CI 1.7 to 2.3) vs 1.06 (CI 1.0 to 1.1), respectively). The difference between the groups was significant (p<001). One case, confirmed as compartment syndrome, showed marked swelling in the muscle group. CONCLUSIONS: Basic ultrasound techniques may be used to identify the site and degree of tissue swelling from cytotoxic envenomation. It is a non-invasive, painless procedure that can assist the clinician to assess the injured limb and may also be of benefit to monitor the progression of swelling.

Osteonecrosis of Interphalangeal Joint of Thumb Two Months after Rattlesnake Bite.

This case report details the osteonecrosis of the interphalangeal (IP) joint of the thumb two months after a rattlesnake bite. It describes the clinical presentation, imaging studies, histological review, pathology review, and review of literature. Our patient was a fifty-one year-old male who obtained a poisonous snakebite to the thumb. While in the hospital for acute treatment, a blood blister was debrided. He was seen two weeks after discharge for further debridement of epidermolysis. Patient presented one month later with a hand x-ray demonstrating bony erosions, and a bone scan showing active changes in the IP joint of his right thumb. He was taken to the OR for further debridement and definitive diagnosis. Pathology results confirmed osteonecrosis with negative bone cultures. The clinical presentation, diagnosis, and operative management of osteonecrosis offer a unique challenge, especially in a patient presenting with osteonecrosis from a poisonous snakebite.

Negative predictive value of excluding an embedded snake foreign body by ultrasonography.

OBJECTIVE: Numerous reputable sources for healthcare providers advocate routine imaging to rule out an embedded tooth or fang after a snake bite. The objective of this study was to determine whether these foreign bodies can be reliably excluded by bedside ultrasonography. METHODS: All emergency medicine (EM) residents and faculty at a single institution were invited to participate. Two sets of 5 ultrasound gel phantoms were prepared using a method previously validated to have the same density as human tissue. In the first set of 5 phantoms, 1 snake fang was embedded to simulate a retained foreign body. Similarly, in the second set of 5 phantoms, 1 snake tooth was also embedded. Participants were asked to identify the presence or absence of a foreign body in each phantom using bedside ultrasonography. Year of training and confidence in excluding a snake foreign body were also recorded. RESULTS: Each participant (n=27) performed ultrasound imaging on 10 phantoms for a total of 270 samples. Range of experience included postgraduate year 1 (25.9%), postgraduate year 2 (29.6%), postgraduate year 3 (33.3%), and graduates of EM residency (11.1%). The sensitivity and negative predictive value for ruling out an embedded fang was 92.6% and 98.1%, respectively. The sensitivity and negative predictive value for ruling out an embedded tooth was 77.8% and 93.7%, respectively. Among all the phantoms, there was a sensitivity of 85.2% and a negative predictive value of 96%. CONCLUSION: Bedside ultrasonography performed by an EM physician is a feasible option to rule out embedded foreign bodies after a snake bite if imaging is warranted.

Point of care ultrasound strikes again.

The article by Vohra and colleagues, "Sonographic Signs of Snakebites", is reviewed and offers a novel use of ultrasound to assess the severity of soft tissue injury due to crotaline envenomation. The authors have shown the feasibility and potential utility of this modality. Further studies are needed to determine the true value of these sonographic findings and how to apply them to patient care.

Sonographic signs of snakebite.

BACKGROUND: Crotaline snakebites are routinely assessed with serial external examinations. We sought to correlate external findings with changes observed on ultrasound imaging. METHODS: This was a prospective, observational study of consecutive rattlesnake envenomation in patients treated at a single hospital in central California. Information recorded for each case included clinical data, gross external examination, and ultrasound images of tissue edema, localized fluid collections, and video footage of muscle fasciculations. RESULTS: Thirteen patients were enrolled. Ultrasound imaging of the bitten extremity was consistent with external examination of the bitten limb. The most common sonographic finding was subcutaneous tissue edema. Edema and necrosis in 3 patients with rapidly progressive leg swelling spared the deeper muscle layers and fascial planes. In 2 patients with bites on the fingers, edema and tendon involvement were readily visualized using a water-bath technique (placement of the hand in a pool of water, allowing more detailed examination of the tissue planes). CONCLUSION: Ultrasound imaging may allow for a more complete understanding of the local effects of snakebite. We were also able to document normal deeper muscle integrity in cases with diffuse leg edema. More studies are needed to fully elaborate the strengths and limitations of bedside ultrasound as a diagnostic adjunct in envenomation assessment.

Calcific myonecrosis following snake bite: a case report and review of the literature.

INTRODUCTION: Calcific myonecrosis is a rare condition in which muscle in a limb compartment undergoes necrosis and becomes peripherally calcified with central liquefaction. The patient usually presents with a slowly progressive enlarged mass that sometimes can be misdiagnosed as soft tissue sarcoma. Most of the reported cases showed that the disease occurs often after trauma or compartment syndrome. However, the case of calcific myonecrosis following snake bite is rarely reported. CASE PRESENTATION: A 66-year-old Thai woman presented with a gradually progressive enlarged mass over a period of 10 years in her left leg. She had a history of untreated compartment syndrome after she was bitten by a snake (Malayan pit viper) in her left leg when she was 14-years old. At presentation, a plain X-ray showed a large soft tissue mass at the anterior compartment of her left leg. A sheet-like mass with an enlarged central cavity combined with peripheral calcification and cortical erosion of her tibia were observed. A biopsy was performed and the result was negative for neoplastic cells. During a 5-year follow-up, the mass progressively enlarged and then became infected and finally broke through the skin. She was treated by excision of the mass and administration of antibiotics. The wound completed healed at 1 month postsurgery. There was no wound complication or disease recurrence at 1 year postoperation. CONCLUSIONS: The diagnosis of calcific myonecrosis was done by history taking and radiographic interpretation. In an asymptomatic patient the management should be observation and clinical follow-up. A biopsy should be avoided due to the high rate of postoperative infection. Treatment of choice in a symptomatic condition is mass excision.

Adder bite on eyelid along with retained intraorbital fangs.

PURPOSE: Snake bite to the eye is a rare event. Most cases reported in the literature are due to boa constrictor bites. This is a rare case of snake bite from a common adder (Vipera berus) to the ocular adnexa along with a retained intraorbital tooth. METHOD: A 57-year-old man presented with a history of being bitten by an adder in the left eye upper lid 12 days previously while bending down to pick up a log at his farm. He developed a firm, tender lump in the medial part of his left upper eyelid. RESULT: A CT scan revealed an extraconal curved calcific dense foreign body, about 5 mm in length consistent with adder's tooth in the superomedial part of left orbit. CONCLUSION: There are few reports of adder bites on face, ear and neck. We report a rare case of adder bite on eyelid along with retained intraorbital fangs and its clinical outcome.

Exotic pathology of the hand and foot. A pictorial review.

In this article, the imaging findings of the most frequently encountered import pathology of the hand and foot are reviewed, including leprosy, loiasis, snake bites or penetration of spines of sea urchins in the hand and foot. Our objective is to familiarize the radiologist of the Western countries with these diseases, which are still prevalent in developing areas. Due to the rising traveling to foreign countries and continuous immigration, it is important that these disorders be considered in the differential diagnosis in a specific population of asylum-seekers, economic refugees and any other group of persons traveling around the globe. Imaging findings on conventional radiography will be emphasized.

Reptile bite in pregnancy.

Reptile bites are rarely seen cases in emergency departments. But particularly in the warm summer months, the prevalence is relatively higher in rural areas. Snakebites during pregnancy is little known and only a few cases have been reported in the literature. However, in case of pregnancy, the outcomes may be different both for mother and the fetus. Interestingly, there is limited number of reptile bite cases during pregnancy in the literature. We report here a woman who was bitten at her 28th week of gestation. Obstetric consultation with ultrasonography was performed and seen that fetus was normal according to a 28-week gestation. We infused four vials of antiserum in a period of 1 h in a saline solution. In all, 30 min after the initiation of the antiserum infusion, the lesion started to regress. Her obstetric consultation was repeated 1 h, 36 h, and before discharge were performed and seen that the fetus was normal. After a period of five days, the patient and fetus were evaluated once more, and nothing was abnormal for both.

Cortical blindness: an unusual sequela of snake bite.

Several ophthalmic effects may follow snake bite; this report describes an instance of cortical blindness that resulted from snake bite.

Lymphatic flow rates and first-aid in simulated peripheral snake or spider envenomation.

OBJECTIVES: To demonstrate and define normal lymphatic transit times by lymphoscintigraphy and to evaluate the efficacy of the currently recommended first-aid measures for the management of snake or spider envenomation. SETTING: The nuclear medicine department of a major teaching hospital. PARTICIPANTS AND DESIGN: Twenty-four subjects received either intradermal or subcutaneous injections of 99mtechnetium antimony sulfur colloid (0.1 mL) in both hands/forearms and feet/legs. This simulated a snake or spider bite. Fifteen of the subjects had first-aid in the form of firm bandages and splints applied to an upper and a lower limb immediately after injection. MAIN OUTCOME MEASURES: The progress of the radiotracer was followed with a large field of view gamma camera. If no egress of radiotracer was seen in the bandaged limbs, the subject walked until radioactivity was detected. RESULTS: The mean (+/- SEM) periphery-to-systemic circulation transit time after subcutaneous injection was 58 (+/- 7) minutes. The first-aid was found to be very effective when applied with bandage pressures ranging from 40 to 70 mmHg (5.3-9.3 kPa) in the upper limb and 55 to 70 mmHg (7.3-9.3 kPa) in the lower limb. Lower and higher bandage pressures were ineffective. However, despite first-aid measures, egress of radiotracer, even in the upper limbs, was seen in all subjects who walked for 10 minutes or more. CONCLUSIONS: Firm pressure bandaging is an effective means of restricting the lymphatic flow of toxins after envenomation, provided the bandage is applied within the defined pressure range. Strict limb immobilisation is necessary to minimise lymphatic flow, and walking after upper or lower limb envenomation will inevitably result in systemic envenomation despite first-aid measures.