Investigation of an outbreak of metallo-ß-lactamase producing Pseudomonas aeruginosa linked to the water distribution system in a Hematopoietic Stem Cell Transplantation Unit.

Introduction: Pseudomonas aeruginosa (PA) is an opportunistic pathogen. Metallo-ß-lactamase producing PA (MBL-PA) poses a problematic issue given limited available treatments. In Argentina, it accounts for less than one percent of healthcare-associated infections. Objectives: To describe an outbreak of verona integron-encoded metallo-ß-lactamase (VIM) Pseudomonas aeruginosa in a Hematopoietic Stem Cell Transplantation Unit (HSCTU), and the strategies implemented to control it. Materials and methods: Investigation of an outbreak by MBL-PA in an HSCTU in May 2023. Active case search, environmental sampling, identification and susceptibility pattern of strains, mitigation strategies. Case: patient admitted to the HSCTU with positive sample for MBL-PA after 48 hours of admission. Mitigation strategies: biweekly rectal swabbing, contact precautions, dedicated nursing staff, waterless patient care, and disinfection of bacterial reservoirs. Results: In May 2023 two cases were identified. A retrospective search determined an additional case. One (10%) of the environmental samples was positive for VIM type MBL-PA in the drain of the hand hygiene station in the nurse's office. Strains were susceptible to colistin and fosfomycin and intermediate to aztreonam. Incidence density (ID) of colonization and infection by MBL-PA in the HSCTU were .68/1,000 patient-days (pd) and 0, respectively, in the second semester of 2022. In the first semester of 2023, ID rose to 2.93/1,000 pd for colonization and .73/1,000 pd for infection.Mitigation strategies aimed at reducing exposure of immunocompromised hosts to water. No new cases have been identified since. Conclusions: We report an MBL-PA outbreak probably linked to the water distribution system in an HSCTU, and mitigation strategies put in place.

Estado actual del trasplanterenopancreático / Current status of the kidney-pancreas transplant

RESUMEN El trasplante de páncreas es un tratamiento alternativo para la diabetes. Sus modalidades e indicaciones son: 1) trasplante de páncreas simultáneo con riñón para pacientes con diabetes mellitus tipo 1 o con nefropatía diabética en estadio terminalen tratamiento sustitutivo o próximo al mismo; 2) trasplante de páncreas después de riñón parapacientes condiabetes mellitustipo 1 con un trasplante renal funcionante; 3) trasplante de páncreas aislado parapacientes con diabetes mellitustipo 1 con hipoglucemias aperceptivas que requieren internaciones o rescate de terceros. Algunos pacientes con diabetes mellitus tipo 2 seleccionados pueden ser candidatos a trasplante de páncreas. La selección de donantes es muy importante, el donante ideal es fallecido por traumatismo craneoencefálico, menor de 45 años, con un peso entre 30 y 90 kg, con un IMC menor a 30kg/m2, hemodinámicamente estable y sin antecedentes de paro cardiorespiratorio ni hipotensión sostenida. Hay varias estrategias de derivación de la función endócrina (sistémica y portal) y exócrina (entérica o vesical), la más utilizada es la derivación sistémica y entérica. En el manejo perioperatorio se destacan estrategias para mantener una buena presión de perfusión tisular, un control estricto de glucemia, para prevenir la trombosis del injerto debe implementarse un plan de antiagregación y anticoagulación, todo lo anterior junto a una profilaxis antibiótica, antifúngica y antiviral. Los esquemas clásicos de inmunosupresión incluyen una inducción con esteroides y anticuerpos deplecionantes de linfocitos T y un mantenimiento con un triple esquema con esteroides, tacrolimus y micofenolato. La clasificación de Banffdistingue rechazos celulares y humorales. La base del tratamiento del rechazo celular incluye pulsos de esteroides y anticuerpos deplecionantes de linfocitos T, mientras que los rechazos humorales requieren de plasmaféresis e inmunoglobulina endovenosa. Las principales complicaciones postoperatorias son el sangrado, la pancreatitis, la trombosis del injerto y las fístulas anastomóticas. En cuanto a los resultados, el trasplante de páncreas presenta, a cinco años, una supervivencia del paciente del 90% y un 77% del injerto pancreático. Las modalidades de trasplante solitario presentan menor supervivencia alejada del injerto. En Argentina hay una actividad de trasplante de páncreas de entre 60 y 80 trasplantes anuales. La reglamentación del INCUCAIprevé la inscripción anticipada en lista de espera de pacientes con nefropatía terminal con depuración de creatinina menor a 30ml/min.

ABSTRACT Pancreas transplantation is an alternative treatment for diabetes. Its modalities and indications are the following: 1) simultaneous pancreas and kidney transplantation: type 1 diabetes mellitus patients with end-stage diabetic nephropathy (in replacement treatment or close to it); 2) pancreas transplantation after kidney: type 1 diabetes mellitus patients with a functioning kidney transplant; 3) isolated pancreas transplantation: type 1 diabetes mellitus patients with unperceived hypoglycemia requiring hospitalization or rescue by third parties. Some of the screened type 2 diabetes mellitus patients may be pancreas transplantation candidates. Choosing a donor is very important: the ideal donor should be a deceased one who died due to intracranial injury, under 45 years of age, weighing between 30 and 90 kg, with a BMI below 30kg/m2, hemodynamically stable and having no history of cardiopulmonary arrest or sustained hypotension. There exist various strategies to divert the endocrine function (systemic and portal) and the exocrine function (vesical or enteric), systemic and enteric diversion being the most commonly used. Among the techniques which stand out during perioperative management, we could mention maintaining a good tissue perfusion, a strict glycemic control, an antiaggregation/anticoagulation plan to prevent graft thrombosis and antibiotic, antifungal and antiviral prophylactic treatment. Classic immunosuppression schemes consist of induction with T cell depleting steroids and antibodies and keeping a three-drug treatment including steroids, tacrolimus and mycophenolate. Banff classification draws a distinction between cellular and humoral rejection. The basis for cellular rejection treatment includes steroid-pulse therapy and T-cell depleting antibodies, while humoral rejection requires plasmapheresis and endovenous immunoglobulin. The main postoperative complications are bleeding, pancreatitis, graft thrombosis and anastomosis fistula. As for the results, the survival rate 5 years after pancreas transplantation is 90% for patients and 77% for pancreatic grafts. Isolated transplantation presents a lower long-term survival of the graft. In Argentina, between 60 and 80 pancreas transplants are performed every year. INCUCAI regulations provide for early registration on the waiting list for patients suffering from end-stage nephropathy with a creatinine clearance lower than 30 mL/min.

Anti-Hla donor-specific antibody monitoring in pancreas transplantation: Role of protocol biopsies.

In kidney transplantation, de novo donor-specific antibodies (DSA) correlate with poor graft survival, and Consensus Guidelines recommend a protocol biopsy. In pancreas transplantation, DSA are also associated with poor graft outcomes; however, there are no recommendations on protocol biopsies. We started an antibody screening protocol on pancreas transplant patients at 0, 3, 6, 12 months, and yearly. Patients with DSA or high MFI non-DSA were considered for protocol biopsies of both organs. Results: 143 pancreas recipients were screened. 84 patients had negative antibodies throughout the study, 11 patients were found to have antibodies at graft dysfunction, and 48 patients had positive antibodies at screening without acute organ dysfunction (study group). Among the 30 non-DSA patients, 9 had protocol simultaneous pancreas and kidney biopsies performed with negative results in all of them. In contrast, among the 18 DSA patients, 15 had these biopsies performed, and 47% presented with subclinical rejection of the kidney, the pancreas, or both. In addition, some of the DSA patients without a protocol biopsy presented with rejection during the first 15 months of follow-up. Conclusion: We conclude that protocol biopsies of both grafts may play a role in the follow-up of pancreas transplant patients with de novo DSA appearance.

Graft dysfunction in simultaneous pancreas kidney transplantation (SPK): Results of concurrent kidney and pancreas allograft biopsies.

Simultaneous pancreas and kidney transplants offer significant therapeutic advantages but present a diagnostic approach dilemma in the diagnosis of rejection. Because both organs are from the same donor, the kidney has been treated traditionally as the "sentinel" organ to biopsy, presumably representing the status of both allografts. Truly concurrent biopsy studies, however, are needed to confirm this hypothesis. We examined 101 concurrent biopsies from 70 patients with dysfunction in either or both organs. Results showed concurrent rejection in 23 of 57 (40%) of cases with rejection; 19 of 57 (33.5%) and 15 of 57 (26.5%) showed kidney or pancreas only rejection, respectively. The degree and type of rejection differed in the majority (13 of 23, 56.5%) of cases with concurrent rejection, with the pancreas more often showing higher rejection grade. Taking into account pancreas dysfunction, a positive kidney biopsy should correctly predict pancreas rejection in 86% of the instances. However, the lack of complete concordance between the 2 organs, the discrepancies in grade and type of rejection, and the tendency for higher rejection grades in concurrent or pancreas only rejections, all support the rationale for pancreas biopsies. The latter provide additional data on the overall status of the organ, as well as information on nonrejection-related pathologies.

Nefropatía por IgA. revisión y conducta terapéutica a propósito de un caso clínico / Therapeutic management of an IgA nephropathy case and disease review

La Nefropatía por Inmunoglobulina A (NIgA), también conocida como enfermedad de Berger, fue descrita por primera vez en 1968 por Berger e Hinglais. Se trata de una enfermedad heterogénea, tanto desde el punto de vista clínico, como histológico, caracterizada por la presencia de depósitos mesangiales de IgA. La clínica de presentación es extremadamente variable, pudiendo manifestarse desde microhematuria aislada hasta un deterioro agudo de la función renal por una glomerulonefritis extracapilar superpuesta. Inicialmente se la consideraba una entidad de buen pronóstico, pero con el paso del tiempo y a partir de un mayor conocimiento de la NIgA, se constató que la realidad era otra y que del 20 al 30% de los pacientes a los 20 años evolucionaban a la insuficiencia renal crónica (IRC) terminal y otro 20% mostraba una pérdida significativa de la función renal. En el presente artículo se describe un caso clínico de un paciente en el que se detectan casualmente marcadores de daño renal en la orina, y en quien los hallazgos histológicos observados en la biopsia renal modificaron su pronóstico y la conducta terapéutica. A partir de este caso clínico se realiza una actualización sobre la Nefropatía por IgA

Inmunoglobulin A (NIgA) Nephropathy also known as Berger disease, was described for the first time in 1968 by Berger and Hinglais. It is a heterogeneous disease, not only from clinical point of view but also from the histologicalone. Characterized by the presence of IgA mesangials deposits. Clinical presentation is extremely variable and can vary from isolated microhematuria up to a severe damage of renal function due to superimposed extracapillary glomerulonephritis. Initially it was considered an entity with good prognosis, but over time and more knowledge about IgAN, it was shown that 20 to 30% of 20 years old patients evolved to end stage renal failure and other 20% had important renal function loss. In the present article we describe a case of a patient in whom we detected by chance renal damage markers in the urine, and then the histologic findings observed in renal biopsy, modified the prognosis and therapeutic procedure. From this clinical case, we performed an update on IgA Nephropathy

[Clinical practice guideline for ANCA-associated vasculitis with renal involvement]. / Vasculitis asociada a ANCA con compromiso renal: guía de práctica clínica.

The ANCA-associated vasculitis (AAV) is a group of systemic conditions characterized by inflammation and necrosis in small and medium vessels. AAV with different levels of disease severity could respond to different therapeutics protocols. Early diagnosis and treatment could significantly improve the outcome of the disease. The objective was to investigate the quality evidence in different therapeutical protocols proposed to AAV with renal involvement in pediatrics and adults patients and evaluate the ANCA applicability in AAV diagnosis and outcome. Using methodological search filters, we identified literature in Medline, Embase, Lilacs and Cochrane Trials Register published between 1997 and July 2015. From 4236 articles, 59 were included. The quality of evidence was assessed using the check list designed by the Cochrane Renal Group. The strength of recommendation was determinated by Levels of Evidence (Oxford Centre for Evidence-based Medicine). On the basis of current evidence, 20 recommendations were elaborated for the treatment and monitoring of patients with AAV with renal involvement in several clinical scenarios, in order to provide physicians a rational approach in daily clinical practice.

Hypercalcemia secondary to granulomatous disease caused by the injection of methacrylate: a case series.

Association of dysregulated calcium homeostasis and granulomatous disease is well established. There exist reports in the literature of granulomatous reactions produced by silicones associated with hypercalcemia. In this case series we report four young women that underwent methacrylate injections in gluteus, thighs and calves that developed granulomas with posterior appearance of hypercalcemia. This complication presented as subacute around 6 months after the procedure. The four patients have as common elements the presence of moderate to severe renal insufficiency, suppressed PTH and elevated calcitriol levels for the degree of renal function. In the image studies, two patients presented in the nuclear magnetic resonance of the gluteus hypodense nodular images compatible with granulomas. Two patients had a positron emission tomography performed showing increased metabolic activity in the muscles of the gluteal region compatible with granulomas. Two patients had a partial surgical resection of the gluteal lesions with the finding of methacrylate associated to foreign body granulomas. In these patients hypercalcemia was treated with oral or local injections of corticoids, intravenous bisphosphonates or ketoconazole with good response. Although the prevalence of this complication with methacrylate injection is not common, hypercalcemia secondary to granulomas should be considered in the differential diagnosis of patients with hypercalcemia when there is a history of this procedure, and especially if they have a reduction in their renal function.