The Use of High Initial Doses of Botulinum Toxin Therapy for Cervical Dystonia Is a Risk Factor for Neutralizing Antibody Formation—A Monocentric Cross-Sectional Pilot Study

Background and Objectives: The present study aims to analyze the complex patient/treating physician interaction at onset of botulinum toxin (BoNT) therapy in patients with idiopathic cervical dystonia (CD) and the influence of high initial doses on long-term outcomes. Materials and Methods: A total of 74 CD patients with well-documented courses of BoNT treatment were consecutively recruited after written informed consent. Patients had to rate the amount of improvement of CD in percent of severity of CD at onset of BoNT therapy. They had to draw the course of disease severity (CoD) of CD from the onset of symptoms until the onset of BoNT therapy and from the onset of BoNT therapy until recruitment. The remaining severity of CD was estimated by the treating physician using the TSUI score. Demographic- and treatment-related data were extracted from the charts of the patients. Seventeen patients with suspected secondary treatment failure (STF) were tested for the presence of antibodies. Results: Depending on the CoD before BoNT therapy, three patient subgroups could be distinguished: rapid onset, continuous onset and delayed onset groups. Time to BoNT therapy, increase in dose and improvement were significantly different between these three groups. In the rapid onset group, with the highest initial doses, the best improvement was reported, but the highest number of patients with an STF and with neutralizing antibodies was also observed. Conclusion: The use of high initial doses in the BoNT therapy of CD is associated with a rapid response and quick success; however, it leads to an elevated risk for the development of a secondary treatment failure and induction of neutralizing antibodies.

Significant Long-Lasting Improvement after Switch to Incobotulinum Toxin in Cervical Dystonia Patients with Secondary Treatment Failure

Under continuous long-term treatment with abo- or onabotulinum toxin type A (BoNT/A), ~10 to 15% of patients with cervical dystonia (CD) will develop neutralizing antibodies and reduced responsiveness over an ~10-year treatment period. Among the botulinum neurotoxin type A preparations so far licensed for CD, incobotulinum toxin A (incoBoNT/A; Xeomin®) is the only one without complex proteins. Whether CD patients with treatment failure under abo- or onaBoNT/A may still respond to incoBoNT/A is unknown. In this cross-sectional, retrospective study, 64 CD patients with secondary treatment failure after abo- or onaBoNT/A therapy who were switched to incoBoNT/A were compared to 34 CD patients exclusively treated with incoBoNT/A. The initial clinical severity of CD, best outcome during abo- or onaBoNT/A therapy, severity at the time of switching to incoBoNT/A and severity at recruitment, as well as all corresponding doses, were analyzed. Furthermore, the impact of neutralizing antibodies (NABs) on the long-term outcome of incoBoNT/A therapy was evaluated. Patients significantly improved after the switch to incoBoNT/A (p < 0.001) but did not reach the improvement level obtained before the development of partial secondary treatment failure or that of patients who were exclusively treated with incoBoNT/A. No difference between abo- and onaBoNT/A pretreatments or between the long-term outcomes of NAB-positive and NAB-negative patients was found. The present study demonstrates significant long-term improvement after a switch to incoBoNT/A in patients with preceding secondary treatment failure after abo- or onaBoNT/A therapy and confirms the low antigenicity of incoBoNT/A.

Analysis of the Physicochemical Characteristics of Distillery Wastewater at Habib Sugar Mills, Nawabshah

The aim of this study is to perceive the level of significant physicochemical characteristics of Distillery Wastewater (DWW) at Habib Sugar Mills, Nawabshah, Pakistan. Five locations in the mill namely spent wash, digester tank, distillery, primary treatment, and secondary treatment were selected for analysis of pH, Total Dissolved Solids (TDS), Total Suspended Solids (TSS), and Chemical Oxygen Demand (COD) of the samples. The samples were taken on a weekly basis for four succeeding months, from January 2021 to April 2021 and the experiments were carried out in the laboratory by adopting standard procedures. The results revealed that the pH of the samples from spent wash was the lowest, whereas secondary treatment samples had the highest. On the contrary, the highest concentrations of TDS, TSS, and COD were found in the samples taken from the spent wash and the lowest from the secondary treatment. The pH values were found abruptly increasing in the digester tank due to the addition of calcium carbonate in the stream of wastewater after the spent wash. The COD concentration was found to rapidly decrease, from more than 106000mg/l in the spent wash to around 35000mg/l in the digester tank samples, and then to gradually decrease up to the final point of disposal. Overall, TDS, TSS, and COD values were higher during April, January, and February and lower during March. The level of pH was extremely low in the spent wash and did not meet the lower limits of standards and the other examined parameters exceeded the upper limits of WHO standards.

Secondary Treatment of Facial Asymmetry in Hemifacial Microsomia

Hemifacial microsomia is most often diagnosed at birth and comprises varying degrees of malformations of one side of the face. Depending on the malformations involved, multiple procedures are required as primary treatment approaches, often embedded in an interdisciplinary concept from birth to adolescence. However, with regard to the symmetry of the face, soft tissue and bony discrepancies between the normal and the affected side often remain recognizable or even persist after surgery, resulting in lasting disturbed facial harmony. Such patients may have a high burden of disease. In our case report, we present the clinical course of a 39-year-old female with hemifacial microsomia, who was suffering persistent facial asymmetry after primary treatment comprising surgery on the mandible and soft tissue augmentation with the use of a free muscle flap. By means of virtual planning tools and patient-specific implants for genioplasty and bony augmentation in a first step followed by soft tissue augmentation with autologous fat cells in a second step, a very satisfactory result was achieved for both patient and medical staff. Hence, for secondary treatment of facial asymmetry in adulthood, a combined and step-by-step therapy addressing both soft and hard tissue seems to be the key to success.

Cost-effectiveness of using stone cone, balloon dilator, stone basket, and entrapment device in ureteroscopic laser lithotripsy for ureteric stones

Objective To evaluate the costs and stone-free rates of ureteroscopic laser lithotripsy (ULL) performed with and without auxiliary equipment and to compare first-time ULL with total treatment. Methods One hundred patients who underwent first-time ULL without the use of auxiliary equipment because its unavailability comprised the no-device ULL (ndULL) group. Additionally, 100 patients who underwent first-time ULL with the use of auxiliary equipment when necessary comprised the device ULL (dULL) group. Results In the ndULL and dULL groups, the stone-free rates after first-time ULL were 72% and 94% and the mean cost was US $1037 ± 15.10 and US $1452 ± 19.80 per case, respectively, with a statistically significant difference. The stone-free rates at the end of treatment were 98% and 99%, respectively, without a statistically significant difference. When secondary treatment costs were added to the first ULL costs after failed treatment, the mean total cost was US $1625 ± 12.60 in the ndULL group and US $1566 ± 11.01 in the dULL group without a statistically significant difference. Conclusions The stone-free rates and costs after first-time ULL were significantly different between the groups. However, after total treatment, there was no statistically significant difference between the two groups.

Antibiotic Resistance Genes and Potentially Pathogenic Bacteria in the Central Adriatic Sea: Are They Connected to Urban Wastewater Inputs?

Despite last decades’ interventions within local and communitarian programs, the Mediterranean Sea still receives poorly treated urban wastewater (sewage). Wastewater treatment plants (WWTPs) performing primary sewage treatments have poor efficiency in removing microbial pollutants, including fecal indicator bacteria, pathogens, and mobile genetic elements conferring resistance to antimicrobials. Using a combination of molecular tools, we investigated four urban WWTPs (i.e., two performing only mechanical treatments and two performing a subsequent conventional secondary treatment by activated sludge) as continuous sources of microbial pollution for marine coastal waters. Sewage that underwent only primary treatments was characterized by a higher content of traditional and alternative fecal indicator bacteria, as well as potentially pathogenic bacteria (especially Acinetobacter, Coxiella, Prevotella, Streptococcus, Pseudomonas, Vibrio, Empedobacter, Paracoccus, and Leptotrichia), than those subjected to secondary treatment. However, seawater samples collected next to the discharging points of all the WWTPs investigated here revealed a marked fecal signature, despite significantly lower values in the presence of secondary treatment of the sewage. WWTPs in this study represented continuous sources of antibiotic resistance genes (ARGs) ermB, qnrS, sul2, tetA, and blaTEM (the latter only for three WWTPs out of four). Still, no clear effects of the two depuration strategies investigated here were detected. Some marine samples were identified as positive to the colistin-resistance gene mcr-1, an ARG that threatens colistin antibiotics’ clinical utility in treating infections with multidrug-resistant bacteria. This study provides evidence that the use of sole primary treatments in urban wastewater management results in pronounced inputs of microbial pollution into marine coastal waters. At the same time, the use of conventional treatments does not fully eliminate ARGs in treated wastewater. The complementary use of molecular techniques could successfully improve the evaluation of the depuration efficiency and help develop novel solutions for the treatment of urban wastewater.