WHO informal consultation on revision of guidelines on evaluation of similar biotherapeutic products, virtual meeting, 30 June - 2 July 2021.

The WHO informal consultation was held to promote the revision of WHO guidelines on evaluation of similar biotherapeutic products (SBPs) adopted by the Expert Committee on Biological Standardization (ECBS) in 2009. It was agreed in the past consultations that the evaluation principles in the guidelines are still valid, but a review was recommended to provide more clarity and case-by-case flexibility. The opportunity was therefore taken to review the experience and identify areas where the current guidance could be more permissive without compromising its basic principles, and where additional explanation could be provided regarding the possibility of reducing the amount of data needed for regulatory approval. The meeting participants applauded the leading role taken by the WHO in providing a much-needed streamlined approach for development and evaluation of SBPs which will provide efficient and cost-effective product development and increase patient access to treatments. It was recognized that the principles as currently described in the draft WHO guidelines are based on sound science and experience gained over the last fifteen years of biosimilar approvals. However, since these guidelines when finalised will constitute the global standard for biosimilar evaluation and assist national regulatory authorities in establishing revised guidance and regulatory practice in this complex area, it was felt that further revision and clarity on certain perspectives in specific areas was necessary to dispel uncertainties arising in the current revised version. This report describes the principles in the draft guidelines, including topics discussed and consensus reached.

Zeolite-based monoliths for water softening by ion exchange/precipitation process.

In this work, the design of a monolithic softener obtained by geopolymer gel conversion is proposed. The softener used consists in a geopolymeric macroporous matrix functionalized by the co-crystallization of zeolite A and X in mixture. The dual nature of the proposed material promotes a softening process based on the synergistic effect of cation exchange and alkaline precipitation. A softening capacity of 90% and 54% for Ca2+ and Mg2+ respectively was attained in 24 h. In fact, the softener reported a Cation Exchange Capacity (CEC) value of 4.43 meq g-1. Technical features such as density, porosity and mechanical resistance were also measured. The use of this monolithic softener can improve performance and sustainability of hardness removal from tap water, reducing the production of sludge and adding the possibility to partially regenerate or reuse it.

Effect of carbonaceous fillers on adsorption behavior of multifunctional diatomite-based foams for wastewater treatment.

Nowadays the study of the potential applications of multifunctional materials for environmental remediation is one of the main goals of the materials engineering. Multifunctional porous materials, MPMs, incorporate, all in once, different and multiple functionalities that make them suitable for several uses and can satisfy many purposes at the same time. Multifunctional diatomite-based foams with a hierarchical porosity, already produced and characterized to be applied in building as well as aerospace sectors, are proposed as adsorbents for inorganic and organic pollutants removal from wastewaters. Then, the effect of the addition of different carbonaceous nanofillers (graphite, graphene and graphene oxide) on the water purification efficiency of the adsorbent was evaluated. Firstly, pristine MPM showed the best performance in adsorbing Indigo Carmine due to its intrinsic chemism and hierarchical porosity (at macro-, micro- and nano-level), but it is not the best with respect to the Cd2+ adsorption, if compared with the nanocomposites. Among the nanocomposite products, both graphene- and graphene oxide-MPM samples showed a significantly improved adsorption capacity towards Cd2+. This behavior is due to the synergistic effect of the finer morphology, higher available foam surface, and the highly exfoliated fillers, graphene and graphene oxide, which permit a better dispersion into the matrix.

Percutaneous implant of Denver peritoneo-venous shunt for treatment of refractory ascites: a single center retrospective study.

OBJECTIVE: Refractory ascites is defined as a lack of response to high doses of diuretics or the development of diuretic related side effects, which compel the patient to discontinue the diuretic treatment. Current therapeutic strategies include repeated large-volume paracentesis and transjugular intrahepatic portosystemic shunts (TIPS). Peritoneovenous shunt (Denver shunt) should be considered for patients with refractory ascites who are not candidates for paracentesis or TIPS. This study presents our case series in the implant of Denver peritoneovenous shunt. PATIENTS AND METHODS: Sixty-two patients underwent percutaneous placement of Denver shunt between November 2003 and July 2014. There were 36 men and 26 women. Ascites was secondary to alcoholic cirrhosis in six patients, cryptogenic cirrhosis in six, and virus-related cirrhosis in fifty of them. Liver cirrhosis was classified as Child B in 22 patients and Child C in 40 (no patient was Child A). RESULTS: All implants were successfully performed. There were no intraoperative problems or lethal complications; our patients were hospitalized for 2 or 3 days. Postoperative complications included: infection of the shunt in 3 patients (4.8%), shunt obstruction in 4 (6.4%) and transient abdominal pain in 4 (6.4%). Significant symptomatic relief was obtained in all patients. CONCLUSIONS: The percutaneous placement of a Denver shunt is a technically feasible and effective method for symptomatic relief of refractory ascites.

Health effects of occupational exposure to acrylamide using hemoglobin adducts as biomarkers of internal dose.

OBJECTIVES: This study assessed the health effects of occupational acrylamide exposure using hemoglobin (Hb) adducts as biomarkers of internal dose. METHODS: Two hundred and ten tunnel workers exposed for about 2 months to a chemical-grouting agent containing acrylamide and N-methylolacrylamide underwent a health examination. Blood samples were drawn for the analysis of Hb adducts of acrylamide. Fifty workers claiming recently developed or deteriorated symptoms of the peripheral nervous system (PNS) were referred to a neurophysiological examination. Workers with Hb-adduct levels exceeding 0.3 nmol/g globin attended follow-up examinations 6, 12, and 18 months after exposure cessation. RESULTS: Forty-seven workers had Hb-adduct levels within the normal background range (0.02-0.07 nmol/g globin), while the remaining 163 had increased levels up to a maximum of 17.7 nmol/g globin. Clear-cut dose-response associations were found between the Hb-adduct levels and PNS symptoms. Thirty-nine percent of those with Hb-adduct levels exceeding 1 nmol/g globin experienced tingling or numbness in their hands or feet. A no-observed adverse effect level of 0.51 nmol/g globin was estimated for numbness or tingling in the feet or legs. For 23 workers there was strong evidence of PNS impairment due to occupational exposure to acrylamide. All but two had recovered 18 months after the cessation of exposure. CONCLUSIONS: Occupational exposure to a grouting agent containing acrylamide resulted in PNS symptoms and signs. The use of Hb adducts of acrylamide as a biomarker of internal dose revealed strong dose-response associations. The PNS symptoms were, however, generally mild, and in almost all cases they were reversible.

Effect of acid precipitation on retention and excretion of elements in man.

From a population of 8918 farmers, 237 were selected whose consumption of locally produced foods was high. The subjects' water sources, private wells, were of different degrees of acidity. Significant associations between pH (median 6.7, range 4.7-8.6) of the drinking water and element concentrations were found. The correlation was negative for aluminium (Al; median 0.07 mumol/l), cadmium (Cd; 0.44 nmol/l), copper (Cu; 0.24 mumol/l) and lead (Pb; 1.9 nmol/l), and positive for calcium (Ca; 0.62 mmol/l) and magnesium (Mg; 0.21 mmol/l). Associations could not be found between the pH of, or element concentrations in, the water and concentrations of A1 (0.17 mumol/l), Mg (0.86 mmol/l) and selenium (Se; 1.0 mumol/l) in plasma, Cd (2.0 nmol/l), Pb (0.19 mumol/l) and mercury (Hg; 13 nmol/l) in blood, or A1 (12 mumol/mol creatinine) and Cu (11 mumol/mol creatinine) in urine. The concentrations of Hg in blood and Se in plasma were related to fish consumption, Cd and Pb in blood to smoking, A1 in urine to antacid intake, Pb in blood to rifle activities and hunting, and Hg in blood to hunting. Acid precipitation has an effect on element concentrations in drinking water, but not on the retention of those elements in the subjects investigated.

[Circumscribed peritonitis of colonic origin]. / Peritoniti circoscritte di origine colica.

The Authors present their personal experience of circumscribed peritonitis of colic origin. They review some physiopathological aspects of these peritonitis and then emphasize the new therapeutic possibilities offered by percutaneous prick echo or TC guided.