Esophagogastric junction outflow obstruction: Where are we now in diagnosis and management?

Esophagogastric junction outflow obstruction (EGJOO) is a major motility disorder based on the Chicago Classification of esophageal motility disorders. This entity involves a heterogenous group of underlying etiologies. The diagnosis is reached by performing high-resolution manometry. This reveals evidence of obstruction at the esophagogastric junction, manifested by an elevated integrated relaxation pressure (IRP) above a cutoff value (IRP threshold varies by the manometric technology and catheter used), with preserved peristalsis. Further tests like endoscopy, timed barium esophagram, and cross-sectional imaging can help further elucidate the underlying etiology and rule out mechanical causes. Treatment is tailored to the underlying cause. Similar to achalasia, treatment targeting lower esophageal sphincter disruption like pneumatic dilation, peroral endoscopic myotomy, and botulinum injection are used in patients with functional EGJOO and persistent symptoms.

Effective and rapid treatment of wound botulism, a case report.

BACKGROUND: The latest news shows several cases of contaminated heroin that is found in different parts all over Europe. This information can be helpful for the emergency doctors to find the correct diagnosis of wound botulism in patients who are intravenous drug users. CASE PRESENTATION: We describe a case of a 40-year-old man who presented to the emergency department in 2016. He suffered from mild dysarthria, diplopia, dysphagia and ptosis since two days. The CT-scan of the cerebrum and the liquor were without any pathological results. We found out that the patient is an intravenous drug user and the clinical examination showed an abscess in the left groin. So we treated him with the suspected diagnosis of wound botulism. In the emergency operation we split the abscess, made a radical debridement and complementary treated him with a high dose of penicillin g and two units of botulism antitoxin. The suspected diagnosis was confirmed a few days later by finding the Toxin B in the abscess and in the patient's serum. In the following days the neurological symptoms decreased and the wound healing was without any complications. The patient left the hospital after nine days; the antibiotic therapy with penicillin g was continued for several days. In a following examination, 14 days after the patient's discharge of the hospital, no further symptoms were found and the abscess was treated successfully without any problems. CONCLUSION: Because wound botulism is a very rare disease it can be challenging to the attending physician. This case shows a fast treatment with full recovery of the patient without any further disabilities, which can be used for the future.

mRNA mediates passive vaccination against infectious agents, toxins, and tumors.

The delivery of genetic information has emerged as a valid therapeutic approach. Various reports have demonstrated that mRNA, besides its remarkable potential as vaccine, can also promote expression without inducing an adverse immune response against the encoded protein. In the current study, we set out to explore whether our technology based on chemically unmodified mRNA is suitable for passive immunization. To this end, various antibodies using different designs were expressed and characterized in vitro and in vivo in the fields of viral infections, toxin exposure, and cancer immunotherapies. Single injections of mRNA-lipid nanoparticle (LNP) were sufficient to establish rapid, strong, and long-lasting serum antibody titers in vivo, thereby enabling both prophylactic and therapeutic protection against lethal rabies infection or botulinum intoxication. Moreover, therapeutic mRNA-mediated antibody expression allowed mice to survive an otherwise lethal tumor challenge. In conclusion, the present study demonstrates the utility of formulated mRNA as a potent novel technology for passive immunization.

Recent developments with metalloprotease inhibitor class of drug candidates for botulinum neurotoxins.

Botulinum Neurotoxins are the most poisonous of all toxins with lethal dose in nanogram quantities. They are potential biological warfare and bioterrorism agents due to their high toxicity and ease of preparation. On the other hand BoNTs are also being increasingly used for therapeutic and cosmetic purposes, and with that the chances of accidental overdose are increasing. And despite the potential damage they could cause to human health, there are no post-intoxication drugs available so far. But progress is being made in this direction. The crystal structures in native form and bound with substrate peptides have been determined, and these are enabling structure-based drug discovery possible. High throughput assays have also been designed to speed up the screening progress. Substrate-based and small molecule inhibitors have been identified. But turning high affinity inhibitors into clinically viable drug candidates has remained a challenge. We discuss here the latest developments and the future challenges in drug discovery for Botulinum neurotoxins.

Virtual trainer for intra-detrusor injection of botulinum toxin to treat urinary incontinence.

Here we introduce a new virtual reality (VR) based simulation system for training the urological procedure of intra-detrusor botulinum toxin (Botox®) injections into the bladder. 6 cases with different bladder anatomy and 3 subtasks are included in the curriculum; this design is guided by several expert urologists according to clinical needs and experience. These virtual bladder models can be deformed by a cystoscope model or penetrated by a needle model. Data of location and dose per injection are collected during the training. After compared among various options, magnetic motion-tracking devices are chosen and integrated onto replicas of cystoscopic instruments as the VR interface for the specific operation. A web/database based learning management platform (LMP) is developed for online data access and validation studies of the training system.

[Wound botulism in heroin addicts in Germany]. / Wundbotulismus bei Heroinabhängigen in Deutschland.

HISTORY AND ADMISSION FINDINGS: 5 heroin addicts (aged 31-44 years; 1 female, 4 men) presented with a history of blurred vision and diplopia followed by dysarthria. 3 of the patients also developed respiratory failure requiring long-term ventilatory support. Physical examination revealed cranial nerve deficits and abscesses at injection sites in 3 of them. DIAGNOSIS: In 4 patients wound botulism was diagnosed on the basis of symptoms, course of the illness and response to specific treatment. Clostridium botulinum was grown from wound swab in one patient. TREATMENT AND COURSE: Two of the patients, having been injected with antitoxin immediately after admission, were discharged almost symptom-free after only a few days. Adjuvant antibiotics and, in 3 patients, surgical débridement of the abscesses were needed. CONCLUSIONS: Progressive cranial nerve pareses in addicts who inject drugs intravenously or intramuscularly should raise the suspicion of wound botulism and require hospitalization. While indirect demonstration of toxin supports the diagnosis, false-negative results are common.

Preventing ptosis after botulinum treatment.

In a series of 33 blepharospasm patients who had the side effect of ptosis following therapeutic botulinum toxin type A (Botox: Allergan, Inc., Irvine, CA, U.S.A.) injection, we administered 41 injections of human botulinum immune globulin (IG) following injections of the toxin to test the dosage and timing of IG injection and its effectiveness in limiting or avoiding ptosis. An IG dose of 3.2 x 10(-3) international units (IU) per unit of Botox was effective in blocking toxin effect when injected into the same tissue site within 4 hours. An IG dose of 1.6 x 10(-2) to 3.2 x 10(-2) into the levator of the eye having more frequent ptosis in 19 patients reduced the incidence of ptosis to 11%. The fellow (control) eye had a ptosis incidence of 37%. No orbital hemorrhage or other adverse effect occurred from the IG or its injection.

Botulismo por herida en la provincia de Mendoza / Wound botulism in Mendoza

Se presenta una paciente con botulismo por herida, la forma menos frecuente del botulismo humano. Es la primera observación confirmada en Mendoza. Se trata de una paciente de sexo femenino, con el antecedente de herida punzante en rodilla derecha por una rama de árbol caída. Ingresó a terapia intensiva infantil con trastornos deglutorios, somnolencia y dificultad en la marcha. Presentaba además hipotonía generalizada, reflejo fotomotor lento, nistagmus y diplopía. Ante la sospecha de botulismo por herida, se envió material de la misma y sangre para estudio, detectándose en las dos muestras toxina botulímica tipo A. En el cultivo se aisló Clostridium botulinum tipo A. La evolución de la paciente, con el apoyo de asistencia respiratoria mecánica, antibiótico y antitoxina, fue al comienzo satisfactoria, pero falleció bruscamente a los 20 días del ingreso por una descompensación hemodinámica. Se hace una actualización del diagnóstico clínico y muy detalladamente del laboratorio; también algunas consideraciones sobre diagnóstico diferencial, tratamiento y prevención. El botulismo por herida debe sospecharse en aquellos pacientes que tengan factores de riesgo traumático o por abuso de drogas y que presenten trastornos simétricos de los pares craneales y debilidad muscular descendente