Oleo gum resin of Ferula assa-foetida L. ameliorates peripheral neuropathy in mice

Ethnopharmacological relevance

According to the Chinese, European, Iranian and Indian traditional medicines, oleo gum resin of Ferula assa-foetida (asafoetida) has therapeutic effects on different kinds of diseases. Some of these effects are related to the diseases of nervous system such as hysteresis and convulsion. In recent studies, some anti-epileptic and neuroprotective roles were also considered for it and we examined its possible role on treatment of peripheral neuropathy.

Material and methods

in vitro studies were carried out to identify the response of isolated sciatic nerves to different concentrations of oleo gum resin of asafoetida solved in Lock?s solution. Then, in vivo studies were conducted to evaluate its effect on amelioration of peripheral neuropathy in mice. Peripheral neuropathy was induced by intraperiotoneal injection of high doses of pyridoxine in adult Balb/c male mice. Tail flick tests were performed to identify the incidence of neuropathy in animals. After 10 days treatment with asafoetida, the efficiency of treatment was assessed by behavioral, electrophysiological and histological studies.

Results

in vitro experiments confirmed that incubating the nerves in aqueous extract of oleo gum rein of asafoetida increased the amplitude and decreased the latent period of nerve compound action potential (CAP). Nerve conduction velocity (NCV) and amplitude of CAP also improved in asafoetida treated animals. Histological and behavioral studies showed that asafoetida was able to facilitate the healing process in peripheral nerves.

Conclusions

in vitro experiments showed that asafoetida is a nerve stimulant and its administration in neuropathic mice exerted neuroprotecting effects through stimulating axonal regeneration and remyelination and decrement of lymphocyte infiltration.     

Fatal gastrointestinal hemorrhage after a single dose of dabigatran

Introduction. Dabigatran (Pradaxa) is a new oral anticoagulant approved by the Food and Drug Administration (FDA), available internationally and indicated as an alternative to warfarin for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Dabigatran does not require laboratory monitoring and its kinetics allow for a more rapid onset of action with a time to peak concentration of 1.25-1.5 h. We are reporting a fatality resulting from gastrointestinal bleeding after the ingestion of a single dose of dabigatran 150 mg. Case details. A 92-year-old man with a medical history of chronic obstructive pulmonary disease, hypothyroidism, and atrial flutter presented to the emergency department with complaints of weakness and rectal bleeding. He was seen by his Cardiologist the day before and was found to be in new atrial fibrillation. He was prescribed dabigatran 150 mg twice daily for anticoagulation therapy. He took one dose of dabigatran 150 mg at 2200 and woke up the following morning before 0900 with profuse rectal bleeding. The initial vital signs in the emergency department, approximately 11 h after ingestion, were heart rate 72 beats/min, blood pressure 62/30 mmHg, and lab work showed hemoglobin 9.9 g/dL, international normalization ratio (INR) 1.99, blood urea nitrogen (BUN) 66 mg/dL, and creatinine (SCr) 1.4 mg/dL (creatinine clearance (CrCl) 24.2 mL/min). He was resuscitated with intravenous fluids, two units of packed red blood cells, two units of fresh frozen plasma, platelets, and vitamin K 10 mg intravenously. He was also given an unknown dose of erythromycin early in his hospital stay. An actively bleeding gastric ulcer was discovered and treated with local epinephrine injections. Approximately 48 h after his exposure, he received an additional two units of blood to treat his decreasing blood pressure (98/41 mmHg). On day three, his hemoglobin and hematocrit were stable at 10 g/dL and 30%, INR 1.6, he was extubated and off vasoactive medications. Day six of hospitalization, he began having maroon stools, his hemoglobin decreased to 8.1 g/dL and his platelets to 81 × 1000/mcL. On day seven, the hemoglobin decreased to 6.4 mg/dL. Despite aggressive resuscitative efforts and supportive care, he died. Discussion. This case demonstrates the potential of a single dose of dabigatran 150 mg to result in a fatal gastrointestinal hemorrhage. This patient was started on the maximum dose with a CrCl 33.9 mL/min and on admission CrCl 24.2 mL/min, suggesting underlying renal insufficiency.     

The evaluation of the clinical effect of topical St Johns wort (Hypericum perforatum L.) in plaque type psoriasis vulgaris: a pilot study

In this case series, ten patients with plaque-type psoriasis were treated with Hypericum perforatum ointment. The hypericum ointment was applied to one side of each patient's body and the vehicle to the opposite side twice daily for 4 weeks in a single blinded manner. Modified psoriasis area severity index (PASI) scores were significantly lowered where the formulated ointment had been applied. In determining PASI scores, three factors, erythema, scaling and thickness, were evaluated; all were significantly lower where the formulated ointment had been applied (P = 0.01, P = 0.004, P = 0.04). Hypericum perforatum ointment applied twice daily may be effective in reducing PASI scores in mild plaque-type psoriasis, however, further larger studies need be conducted to achieve a more conclusive result.     

A molecularly integrated grade for meningioma

BackgroundMeningiomas are the most common primary intracranial tumor in adults. Clinical care is currently guided by the World Health Organization (WHO) grade assigned to meningiomas, a 3-tiered grading system based on histopathology features, as well as extent of surgical resection. Clinical behavior, however, often fails to conform to the WHO grade. Additional prognostic information is needed to optimize patient management.MethodsWe evaluated whether chromosomal copy-number data improved prediction of time-to-recurrence for patients with meningioma who were treated with surgery, relative to the WHO schema. The models were developed using Cox proportional hazards, random survival forest, and gradient boosting in a discovery cohort of 527 meningioma patients and validated in 2 independent cohorts of 172 meningioma patients characterized by orthogonal genomic platforms.ResultsWe developed a 3-tiered grading scheme (Integrated Grades 1-3), which incorporated mitotic count and loss of chromosome 1p, 3p, 4, 6, 10, 14q, 18, 19, or CDKN2A. 32% of meningiomas reclassified to either a lower-risk or higher-risk Integrated Grade compared to their assigned WHO grade. The Integrated Grade more accurately identified meningioma patients at risk for recurrence, relative to the WHO grade, as determined by time-dependent area under the curve, average precision, and the Brier score.ConclusionWe propose a molecularly integrated grading scheme for meningiomas that significantly improves upon the current WHO grading system in prediction of progression-free survival. This framework can be broadly adopted by clinicians with relative ease using widely available genomic technologies and presents an advance in the care of meningioma patients.     

Occult infection in pseudarthrosis revision after spinal fusion

Background ContextPseudarthrosis after attempted spinal fusion is yet not sufficiently understood and presents a surgical challenge. Occult infections are sometimes observed in patients with pseudarthrosis and no inflammatory signs of infection. The prevalence of such occult infection and its association with patient demographics and inflammatory markers are largely unknown.PurposeTo determine the prevalence of unexpected low-grade infection in spinal pseudarthrosis revision surgery, and to evaluate whether such infection is associated with patient demographics and inflammatory markers.Study DesignRetrospective observational study.Patient SampleOne-hundred-and-twenty-eight patients who underwent thoracolumbar revision surgery due to presumed aseptic pseudarthrosis after spinal instrumentation.Outcome MeasuresCulture-positive infections or noninfectious pseudarthrosis.MethodsSamples were routinely taken for microbiological examination from all adults (n=152) who underwent revision surgery for presumed aseptic thoracolumbar pseudarthrosis between 2014 and 2019. A full intraoperative microbiological workup (at least three intraoperative tissue samples) was done for 128 (84%) patients, and these patients were included in further analyses. Patient characteristics, medical history, inflammatory markers, and perioperative data were compared between those with and without microbiologically-confirmed infection based on samples obtained during pseudarthrosis revision.ResultsThe microbiological workup confirmed infection in 13 of 128 cases (10.2%). The predominant pathogen was Cutibacterium acnes (46.2%), followed by coagulase-negative staphylococci (38.5%). The presence of infection was associated with the body mass index (30.9±4.7 kg/m² [infected] vs. 28.2±5.6 kg/m² [controls], p=.049), surgery in the thoracolumbar region (46% vs. 18%, p=.019), and a slightly higher serum C-reactive protein level on admission (9.4±8.0 mg/L vs. 5.7±7.1 mg/L, p=.031). Occult infection was not associated with age, sex, prior lumbar surgeries, number of fused lumbar levels, American Society of Anesthesiologist score, Charlson Comorbidity Index, presence of diabetes mellitus, and smoking status.ConclusionsOccult infections were found in 10% of patients undergoing pseudarthrosis revision after spinal fusion, even without preoperative clinical suspicion. Occult infection was associated with higher body mass index, fusions including the thoracolumbar junction, and slightly higher C-reactive protein levels. Intraoperative microbiological samples should be routinely obtained to exclude or identify occult infection in all revision surgeries for symptomatic pseudarthrosis of the spine, as this information can be used to guide postoperative antibiotic treatment.     

Residual motion of different posterior instrumentation and interbody fusion constructs

Purpose

To elucidate residual motion of cortical screw (CS) and pedicle screw (PS) constructs with unilateral posterior lumbar interbody fusion (ul-PLIF), bilateral PLIF (bl-PLIF), facet-sparing transforaminal lumbar interbody fusion (fs-TLIF), and facet-resecting TLIF (fr-TLIF).

Methods

A total of 35 human cadaver lumbar segments were instrumented with PS (n = 18) and CS (n = 17). Range of motion (ROM) and relative ROM changes were recorded in flexion/extension (FE), lateral bending (LB), axial rotation (AR), lateral shear (LS), anterior shear (AS), and axial compression (AC) in five instrumentational states: without interbody fusion (wo-IF), ul-PLIF, bl-PLIF, fs-TLIF, and fr-TLIF.

Results

Whereas FE, LB, AR, and AC noticeably differed between the instrumentational states, AS and LS were less prominently affected. Compared to wo-IF, ul-PLIF caused a significant increase in ROM with PS (FE + 42%, LB + 24%, AR + 34%, and AC + 77%), however, such changes were non-significant with CS. ROM was similar between wo-IF and all other interbody fusion techniques. Insertion of a second PLIF (bl-PLIF) significantly decreased ROM with CS (FE -17%, LB -26%, AR -20%, AC -51%) and PS (FE − 23%, LB − 14%, AR − 20%, AC − 45%,). Facet removal in TLIF significantly increased ROM with CS (FE + 6%, LB + 9%, AR + 17%, AC of + 23%) and PS (FE + 7%, AR + 12%, AC + 13%).

Conclusion

bl-PLIF and TLIF show similarly low residual motion in both PS and CS constructs, but ul-PLIF results in increased motion. The fs-TLIF technique is able to further decrease motion compared to fr-TLIF in both the CS and PS constructs.

     

Rare Case of Dysphagia

Wound botulism is exceedingly rare and occurs almost exclusively among injection drug users. In 2008 there was a case of wound botulism in a noninjecting drug user reported to the Centers for Disease Control and Prevention (CDC). We report a case of a Caucasian male developing dysphagia due to wound botulism after having a motorcycle accident that left him with open fractures. The CDC was contacted and the patient was transferred to medical intensive care unit to be emergently started on hepatavalent Clostridium botulinum antitoxin. Early suspicion of wound botulism is essential for effective therapy with antitoxin in this life-threatening disease. If not suspected, this patient would likely have died. Nevertheless, the delay in diagnosis and treatment resulted in the patient’s suffering dysphagia and neurological deficits. The patient required a percutaneous endoscopic gastrostomy tube and months of dysphagia therapy, supportive care, and rehabilitation. Our aim is to increase the awareness for wound botulism when a patient presents with dysphagia and diplopia after suffering open wounds. If suspected early, the morbidity and mortality from this disease can be prevented.