Clinical characteristics & outcome of SARS-CoV-2 infected neonates presenting to paediatric emergency.

Background & objectives: Data on neonatal COVID-19 are limited to the immediate postnatal period, with a primary focus on vertical transmission in inborn infants. This study was aimed to assess the characteristics and outcome of COVID-19 in outborn neonates. Methods: All neonates admitted to the paediatric emergency from August 1 to December 31, 2020, were included in the study. SARS-CoV-2 reverse transcription- (RT)-PCR test was done on oro/nasopharyngeal specimens obtained at admission. The clinical characteristics and outcomes of SARS-CoV-2 positive and negative neonates were compared and the diagnostic accuracy of a selective testing policy was assessed. Results: A total of 1225 neonates were admitted during the study period, of whom SARS-CoV-2 RT-PCR was performed in 969. The RT-PCR test was positive in 17 (1.8%). Mean (standard deviation) gestation and birth weight of SARS-CoV-2-infected neonates were 35.5 (3.2) wk and 2274 (695) g, respectively. Most neonates (11/17) with confirmed COVID-19 reported in the first two weeks of life. Respiratory distress (14/17) was the predominant manifestation. Five (5/17, 29.4%) SARS-CoV-2 infected neonates died. Neonates with COVID-19 were at a higher risk for all-cause mortality [odds ratio (OR): 3.1; 95% confidence interval (CI): 1.1-8.9, P=0.03]; however, mortality did not differ after adjusting for lethal malformation (OR: 2.4; 95% CI: 0.7-8.7). Sensitivity, specificity, accuracy, positive and negative likelihood ratios (95% CI) of selective testing policy for SARS-CoV-2 infection at admission was 52.9 (28.5-76.1), 83.3 (80.7-85.6), 82.8 (80.3-85.1), 3.17 (1.98-5.07), and 0.56 (0.34-0.93) per cent, respectively. Interpretation & conclusions: SARS-CoV-2 positivity rate among the outborn neonates reporting to the paediatric emergency and tested for COVID-19 was observed to be low. The selective testing policy had poor diagnostic accuracy in distinguishing COVID-19 from non-COVID illness.

Population Pharmacokinetics of Fixed Dose Combination of Ceftriaxone and Sulbactam in Healthy and Infected Subjects.

Increased antibacterial resistance (ABR) and limited drug discovery warrant optimized use of available antibiotics. One option is to rationally combine two antibiotics (fixed dose combination (FDC)) that may delay or prevent emergence of ABR in notorious pathogen. Major concern with FDC is the mutual interaction of its components that might influence their pharmacokinetic (PK) profile, requiring reassessing of whole formulation (adding cost and time). The interaction can be identified by comparing PK profile of a drug present in FDC with its independent entity. An open-label, crossover, single-dose comparative PK study of FDC (ceftriaxone and sulbactam) with their individual reference formulations was performed in 24 healthy adult subjects. No mutual PK interactions between ceftriaxone and sulbactam were observed. Pharmacokinetic data was used to develop a population-PK model to understand between-subject variability (BSV). Pharmacokinetics of ceftriaxone/sulbactam was explained by one and two compartment models, respectively. The subject's "weight" was identified as a covariate explaining BSV. Both internal and external validations (healthy/infected subjects) were done. The model-derived population-PK parameters of FDC's active components in infected subjects were similar to literature reported values of individual components. Efficacies of various FDC dosage regimens over a range of minimum inhibitory concentrations (MICs) were assessed by Monte Carlo simulations using population-PK parameters of infected/healthy subjects. In infected subjects, 3 g FDC/24 h can treat bacteria with MIC ≤8 µg/mL, while for MIC 8-32 µg/mL, 3 g FDC/12 h is recommended. Lastly, the developed population-PK model was successfully used to predict drug exposure in pediatric population.

L-asparginase administration reduces white blood cell count and prevents tumor lysis syndrome in children with hyperleukocytic acute lymphoblastic leukemia.

BACKGROUND: The management of hyperleukocytosis currently involves intensive supportive care for preventing tumor lysis syndrome (TLS)-associated metabolic abnormalities as well as cytoreduction procedures to reduce the white blood cell (WBC) count. These procedures are often equipment-intensive and may not be practised in developing countries with limited resources. Hence, it is not clear what would be the most effective strategy to manage hyperleukocytosis and prevent TLS. PROCEDURE: All children ≤12 years, diagnosed with acute lymphoblastic leukemia (ALL) and hyperleukocytosis (WBC count >100 × 10(9)/l) were administered L-asparginase (L-asp, 6,000 U/m(2), i.m.) along with standard supportive care consisting of hydration, oral allopurinol administration and alkalization. The complete blood counts and biochemical parameters were monitored for 72 h. After 48 h, if the WBC count was >100 × 10(9)/l, a repeat dose of L-asp was administered. RESULTS: Twenty-one children (9 boys and 12 girls) with hyperleukocytic ALL were treated with L-asp. The median age of the children was 5.3 years (range 2-11 years). The median initial WBC count was 249 × 10(9)/l (range 151-476 × 10(9)/l). Twenty children received only one dose of L-asp. The mean reduction in WBC count achieved by treatment was 15.7, 42.0, 61.0, 76.4, 85.5 and 90.8% at 12, 24, 36, 48, 60 and 72 h, respectively. None of the patients developed TLS. CONCLUSIONS: Chemical cytoreduction by administering L-asp is an effective means of managing hyperleukocytosis and preventing TLS.

Acute free-floating carotid artery thrombus causing stroke in a young patient: unique etiology and management using endovascular approach.

Atherosclerotic disease accounts for 20%-30% of strokes in the general population. In young adults, it is an unexpected event and its causes involve diverse pathologies. Herein, we describe a unique case of acute embolic stroke in a young adult patient due to the presence of a large clot in the right common and internal carotid arteries, as a result of an extrinsic cause. Surgical clot retrieval was considered unsafe at that point in time in view of the active inflammatory changes surrounding the affected vessels. This was eventually treated with a novel endovascular technique, a unique alternative to open surgery, with excellent clinical outcome. To our knowledge, the penumbra system has never been used for thrombus removal in a nonacute setting.

Modification of the sandwich technique to preserve flow in the hypogastric artery after endovascular repair of aortoiliac aneurysmal disease: our initial experience with two cases.

BACKGROUND: To describe modification of the sandwich technique to preserve flow in the hypogastric artery after endovascular repair of aortoiliac aneurysmal disease in patients with challenging anatomy. METHODS AND RESULTS: The sandwich technique has been proposed as an option in patients with aortoiliac aneurysmal disease, in whom standard iliac branch device may not be technically feasible. We feel that even with the sandwich technique, there are issues with adequately treating these aneurysms in patients with short common iliac arteries with critical landing zones and in those with narrow-caliber external iliac arteries. We describe our experience with two patients we operated on using a modification of the originally described technique and their follow-up. CONCLUSIONS: The modification of the sandwich technique is a promising alternative technique that would be useful in situations where standard endovascular grafts cannot be used in patients with challenging anatomy.

Embolization of carotid-cavernous fistula via direct percutaneous puncture of the inferior ophthalmic vein.

Carotid-cavernous fistulas (CCFs) are anomalous connections between the carotid circulation and the cavernous sinus, and may cause significant morbidity. Endovascular treatment of these lesions can be challenging if typical transvenous routes are inaccessible. We describe a case of a Barrow type D carotid-cavernous fistula in which transvenous embolization was attempted via the inferior petrosal sinus (IPS). No connection was found to the fistula, and the superior ophthalmic vein (SOV) was thrombosed. A novel direct percutaneous puncture of the IOV was performed with ultrasound guidance showing that this is a safe alternative route of CCF access and embolization when the IPS and SOV are inaccessible.

Severe neonatal pulmonary artery hypertension rescued with vasopressin.

An inborn term neonate weighing 2600 g developed meconium aspiration syndrome at birth. Baby had respiratory failure requiring high-frequency oscillatory ventilation support at 15 hours of life. He additionally developed hypotension with left ventricular dysfunction noted on point-of-care echocardiography (POCE), which required dopamine and epinephrine infusions. At 28 hours of life, he was started on inhaled nitric oxide (iNO), followed by milrinone due to hypoxaemic respiratory failure and the POCE revealed severe pulmonary artery hypertension (PAH). As PAH was refractory to iNO and milrinone, vasopressin was added which resulted in rapid improvement in oxygenation and normalisation of pulmonary artery pressures. Baby was weaned off from vasoactive support in the next 120 hours. Vasopressin proved to be the rescue agent in this case of iNO refractory PAH without any side effects during therapy. Baby was successfully extubated on day 18 and was discharged with a normal neurological examination finding.

Revascularization of an occluded brachiocephalic vein using Outback-LTD re-entry catheter.

A 78-year-old man with end-stage renal disease and a right brachial-cephalic upper arm direct hemodialysis access presented with symptomatic central venous occlusion. The right brachiocephalic vein occlusion in this patient was refractory to wire traversal. Sharp recanalization of the central venous occlusion was done with an Outback LTD re-entry catheter (Cordis Corporation, a Johnson & Johnson Company, Miami, Fla). The track was balloon dilated and stented. When the conventional management options fail, this technique may be used to salvage a precious dialysis access and to relieve the patient from symptoms of central venous hypertension.

Long-term follow-up of the treatment of renal angiomyolipomas after selective arterial embolization with alcohol.

STUDY TYPE: Therapy (case series). LEVEL OF EVIDENCE: 4. OBJECTIVE: To present our institution's experience of selective embolization of renal angiomyolipomas with alcohol and the long-term follow up data. PATIENTS AND METHODS: This retrospective study included 34 patients treated between October 1997 and October 2007 (29 women and five men, mean age 44 years). Of these patients, nine had tuberous sclerosis, 14 were bilateral and 16 were multifocal. Indications for treatment were previous haemorrhage (14), size >4 cm (19) and increasing size over a short period (one). The largest treated lesion was 24.4 cm, and the mean (range) size was 11.9 (2.9-24.4) cm. All patients were treated by selective embolization using a mixture of alcohol and lipiodol. Three patients also had coiling of aneurysms and two patients had additional embolization with polyvinyl alcohol particles. The follow-up was both radiological and clinical, with recurrence defined as growth by >2 cm or symptoms requiring further treatment. RESULTS: The technical success rate was 100%, with only one significant complication of non-target renal embolization, with self-limiting effects. Minor complications included 11 patients with post-embolization syndrome, all of which settled with conservative measures. The mean (range) combined radiological and clinical follow-up was 44.2 (12-116) months, with all patients having a follow-up of >1 year. Radiological success was achieved in 97%, with only one lesion growing by >2 cm. The combined clinical and radiological success rate was 85%, with two patients undergoing surgery, two having repeat embolization and one currently offered surgery due to a recent increase in size. CONCLUSION: Our study provides long-term evidence that selective arterial embolization with alcohol is a safe and effective method for improving clinical symptoms (85%) and preventing tumour progression (97%) in patients with renal angiomyolipoma.

Endovenous laser therapy in the treatment of lower-limb venous ulcers.

PURPOSE: To assess the efficacy of endovenous laser therapy (EVLT) in the treatment of lower-limb venous ulcers secondary to venous reflux. MATERIALS AND METHODS: Forty-four of 139 patients referred for EVLT from January 2004 to August 2007 had nonhealing venous ulcers. Preprocedural duplex ultrasound (US) was performed to document saphenous venous reflux secondary to saphenofemoral/saphenopopliteal junction incompetence, deep venous insufficiency, and deep vein thrombosis. Follow-up intervals were within 1 week, monthly until ulcer healing, and every 6 months thereafter. Mean follow-up period was 35.8 months (range, 8.1-59.3 months). RESULTS: Mean great saphenous vein (GSV) diameter and length treated were 9.9 mm (range, 5.5-16.0 mm) and 36.7 cm (range, 20.0-60.0 cm). Mean laser energy used was 3,292 J (range, 1,392-4,971 J). Mean energy deposited per centimeter of vein was 93.6 J/cm (range, 45.2-182.0 J/cm). Mean laser time was 232 seconds (range, 99-347 sec). Fifteen patients with follow-up duplex US had no GSV flow at 6 months, with nonvisualization indicating complete obliteration. Ulcer healing occurred as early as 1 week after the procedure in some patients. Cumulative healing rates at 1, 3, 6, and 12 months were 82.1%, 92.5%, 92.5%, and 97.4%, respectively. No ulcer had recurred at 1 year, but ulcers recurred in five patients at 14, 14, 23, 35, and 52 months after EVLT, respectively. One patient with a nonhealing ulcer 2 years after treatment developed well differentiated squamous cell carcinoma. CONCLUSIONS: Ulcer epithelization occurred with continued GSV occlusion and loss of flow. Most ulcers healed within 3 months with no recurrence at 1 year. Nonhealing ulcers should undergo biopsy to exclude malignant transformation.

Transcranial Doppler in the Detection and Management of Arterial Vasospasm after Aneurysmal Subarachnoid Haemorrhage.

Delayed cerebral ischaemia (DCI) and cerebral infarction is a much-feared complication of aneurysmal subarachnoid haemorrhage (aSAH). It has been largely attributed to focal hypoperfusion from reversible cerebral arterial narrowing, "vasospasm," from the effects of prolonged exposure of the arteries to perivascular blood and oxy-haemoglobin. Transcranial Doppler (TCD) provides a non-invasive method for detecting and monitoring vasospasm. We report a 38-year-old lady who developed sudden dizziness and catastrophic generalised headache with neck pain (Pain Score 10/10) while voiding her bowels. She subsequently became drowsy and was brought to hospital. On examination, she was already alert and orientated. Blood pressure was 175/109 mm Hg. Her neurological examination was normal but for severe neck stiffness to passive flexion. Computed tomography of the brain showed extensive SAH. Cerebral angiography revealed a 6 × 3 mm aneurysm along the posteromedial aspect of the supraclinoid left internal carotid artery. She underwent aneurysm coiling that night. She was given intravenous and then oral nimodipine. TCD monitoring of the circle of Willis on day 14 detected very high velocities in the right and left middle cerebral arteries, mean velocity 187 and 141 cm/s, middle cerebral artery/internal carotid artery ratio 6.03 and 4.15, suggestive of severe and moderate vasospasm, respectively. She did not develop any related neurological symptoms or deficits. She was maintained in a euvolemic state and given high volumes of intravenous saline (2.4 L/day). Repeat TCD 7 days later was normal. The intravenous saline was gradually tailed off and she was subsequently discharged. TCD has an important role in the non-invasive detection and monitoring of vasospasm after aSAH.

Limb-Shaking Transient Ischemic Attacks in a Patient with Previous Bilateral Neck Irradiation: The Role of Collateral Flow.

Nasopharyngeal carcinoma (NPC) is commonly treated with bilateral neck radiation, which is closely associated with the complication of carotid-occlusive disease. This leads to cerebral hemodynamic compromise and possible ischemic stroke. Another manifestation is limb-shaking transient ischemic attacks (LS-TIAs), characterized by rhythmic jerks which can be easily mistaken as a focal motor seizure. We describe a case of unilateral LS-TIAs from bilateral carotid occlusion that resolved with contralateral carotid revascularization. Our patient is a 65-year-old gentleman who had no significant co-morbidities other than a past history of bilateral neck irradiation for NPC 8 years before. He presented with left-sided limb weakness and subsequently left-sided limb involuntary movements whenever he sat up or stood. His symptoms did not respond to anti-epileptic therapy. Clinical and neurological examination was significant for a left pronator drift and weak left finger abduction. Computed tomography and magnetic resonance imaging of the brain revealed infarcts in the right periventricular and watershed areas; MR angiogram showed bilateral internal carotid artery occlusion. Single photon emission computed tomography showed reduced blood flow in the right frontal, temporal, and parietal regions, that reduced further after acetazolamide challenge. He was diagnosed as having LS-TIA secondary to carotid-occlusive disease. Attempts at endovascular opening the right internal carotid artery failed. Following successful left carotid angioplasty and stenting, his symptoms gradually resolved. The left internal carotid artery remained patent at the 3-month follow-up; the right side remained occluded. Our case supports the hypothesis that LS-TIAs are due to hemodynamic compromise and may respond to improved collateral cerebral blood flow.

Small Intracranial Aneurysms and Subarachnoid Hemorrhage: Is the Size Criterion for Risk of Rupture Relevant?

The current understanding is that small intracranial aneurysms (<7 mm) are not at a significant risk for rupture. However, there have been several published series of rupture and subarachnoid hemorrhage from aneurysms <5 mm. Three cases of intracranial aneurysms rupturing at <3 mm are presented in this paper. Patient age ranged between 38 and 57 years. The aneurysms were located in different parts of the circulation in the brain. This case series highlights that the size criterion alone is not adequate when evaluating patients with unruptured brain aneurysms for observational follow-up or treatment.

Isolated Focal Basilar Artery Stenosis with Acute Stroke Treated with Emergency Thrombectomy and Stenting.

Strokes due to basilar artery (BA) stenosis/occlusion are devastating. As it is an uncommon cause of stroke, its optimal management is not clearly defined. We present the case of a 68-year-old male with a background history of hypertension, hyperlipidaemia, and smoking who developed a sudden onset of reduced consciousness, myoclonic jerks, generalised weakness, and nausea due to an occluded mid-segment BA with right occipital and left cerebellar infarcts. Emergent cerebral angiography was performed and he was immediately treated by clot retrieval and, due to underlying arterial stenosis, the immediate placement of a stent within 3 h of symptom onset. He had complete neurological recovery within 1 week, with no neurological deficits. He remained well at follow-up 3 months later. Emergency revascularisation of stroke due to BA occlusion should be considered as a treatment option.

Transcranial Color-Coded Duplex Ultrasound for Assessing Cerebrovascular Reserve in Intracranial Dissection with Aneurysm.

Intracranial artery dissection (IAD) is an uncommon cause of cerebral ischemia. It may lead to symptoms due to rupture of subadventitial aneurysms or thromboembolism from subintimal disruption. Severe stenosis may lead to reduced cerebrovascular reserve (CVR). While there are many methods of assessing CVR, we report a case of IAD with hemodynamic complications diagnosed by transcranial color-coded duplex (TCCD) ultrasonography. Our patient is a 38-year-old female who presented with a 2-month history of nausea, then feeling faint whenever she got up suddenly. On the day of admission, she had gotten up to walk, felt nauseous, and the left upper limb felt "funny," after which she lost consciousness. Clinical and neurological examination was normal. Brain magnetic resonance (MR) imaging was normal. MR angiogram and subsequent computed tomography (CT) angiogram showed flow attenuation in the M1 segment of the right middle cerebral artery (RMCA), with a possible flap. Catheter angiography was suggestive of a dissection with 2.7 mm pseudoaneurysm. TCCD showed very high velocities in the RMCA. The Breath-Holding Index (BHI) was 0.56, suggestive of reduced CVR in the RMCA territory. Acetazolamide-enhanced single-photon emission CT showed reduced right frontal CVR. She was given clopidogrel for secondary prevention, and has remained well. BHI as measured by TCCD is a new method for assessing CVR in patients with cerebral ischemia.

Postnephrectomy fistula between the renal artery stump and inferior vena cava treated with Amplatzer vascular plug: gray-scale and Doppler sonographic findings.

Fistulous communication between the renal artery stump and the inferior vena cava is a rare complication of nephrectomy. We report a case of an adult male in whom a fistula was detected on investigation for persistent postoperative anemia. The fistula was initially identified with Doppler sonography and subsequently confirmed on a catheter angiogram. It was successfully occluded percutaneously with an Amplatzer vascular plug. The plug had a distinctive appearance on subsequent sonographic studies that was useful for follow-up evaluation.

Renal nutcracker syndrome in a young lady: unusual findings and endovascular management.

Nutcracker syndrome (NCS) is caused by compression of left renal vein (LRV), usually between the aorta and the superior mesenteric artery (SMA). This can lead to obstruction of flow into the inferior vena cava and secondary left renal venous hypertension. Despite potential serious consequences, diagnosing NCS is often challenging, circuitous and commonly delayed. We report an extremely unique case of NCS. A 34-year-old woman presented with left flank pain and discomfort. On investigation, it was found that high pressure in the LRV, due to compression by the SMA, had led to a large venous aneurysm that had caused pelviureteric junction obstruction and hydronephrosis. Management was with stenting of the LRV and coil embolisation of the venous aneurysm with excellent clinical outcome.

Biological activities of Ocimum sanctum L. fixed oil--an overview.

Seeds of Ocimum sanctum L. (Labiatae; popularly known as 'Tulsi' in Hindi and 'Holy Basil' in English) contain a pale yellow colored fixed oil. The oil possesses antiinflammatory activity due to dual inhibition of arachidonate metabolism supplemented by antihistaminic activity. The antiinflammatory activity is not dependent on the pituitary adrenal axis. The oil possesses antipyretic activity due to prostaglandin inhibition and peripherally acting analgesic activity. The oil has been found to be effective against formaldehyde or adjuvant induced arthritis and turpentine oil induced joint edema in animals. Lipoxygenase inhibitory, histamine antagonistic and antisecretory activities of the oil contribute towards antiulcer activity. The oil can inhibit enhancement of vascular capillary permeability and leucocyte migration following inflammatory stimulus. The LD50 of the oil is 42.5 ml/kg and long-term use of oil at 3 ml/kg dose does not produce any untoward effects in rats. The oil contains a-linolenic acid, an omega-3 fatty acid, which on metabolism produces eicosapentaenoic acid and the same appears to be responsible for the biological activity. The oil has hypotensive, anticoagulant and immunomodulatory activities. Antioxidant property of the oil renders metabolic inhibition, chemoprevention and hypolipidaemic activity. Presence of linolenic acid in the oil imparts antibacterial activity against Staphylococcus aureus. The oil alone or in combination with cloxacillin, a beta-lactamase resistant penicillin, has been found to be beneficial in bovine mastitis, an inflammatory disorder resulting from staphylococcal infection. Existence of anti-inflammatory, analgesic and antibacterial activities in single entity i.e. fixed oil appears to be unique.

Posterior fossa dural arteriovenous fistula presenting clinically as a carotid-cavernous fistula treated by a direct access cavernous sinus approach.

Dural arteriovenous fistulas (dAVFs) represent approximately 10-15% of all cerebral vascular malformations. Although dAVFs can occur anywhere in the brain, they occur most frequently in the cavernous and transverse-sigmoid sinuses. Posterior fossa dAVFs presenting clinically as carotid-cavernous fistulae (CCF) are rarely encountered in clinical practice. We discuss and illustrate an unusual case of a left posterior fossa dAVF that presented clinically with chemosis and early visual impairment, similar to that of CCF. This was subsequently treated by a direct access cavernous sinus approach. We describe the technique used to access the cavernous sinus directly in cases where conventional transvenous and transarterial routes have been exhausted.