Treatment with rituximab for a patient with p-ANCA glomerulonephritis, alveolar bleeding and multiple relapses during haemodialysis
Tratamiento con rituximab en un paciente con glomerulonefritis p-ANCA, hemorragia alveolar y múltiples recidivas en hemodiálisis
Read
7028
Timeswas read the article
653
Total PDF
6375
Total HTML
Share statistics
array:20 [ "pii" => "X2013251410050798" "issn" => "20132514" "doi" => "10.3265/Nefrologia.pre2010.Aug.10535" "estado" => "S300" "fechaPublicacion" => "2010-11-01" "documento" => "article" "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/" "subdocumento" => "fla" "cita" => "Nefrologia (English Version). 2010;30:710-2" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 4144 "formatos" => array:3 [ "EPUB" => 286 "HTML" => 3459 "PDF" => 399 ] ] "Traduccion" => array:1 [ "es" => array:17 [ "pii" => "X0211699510050790" "issn" => "02116995" "doi" => "10.3265/Nefrologia.pre2010.Aug.10535" "estado" => "S300" "fechaPublicacion" => "2010-11-01" "documento" => "article" "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/" "subdocumento" => "fla" "cita" => "Nefrologia. 2010;30:710-2" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 6056 "formatos" => array:3 [ "EPUB" => 300 "HTML" => 5075 "PDF" => 681 ] ] "es" => array:9 [ "idiomaDefecto" => true "titulo" => "Tratamiento con rituximab en un paciente con glomerulonefritis p-ANCA, hemorragia alveolar y múltiples recidivas en hemodiálisis" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "710" "paginaFinal" => "712" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Treatment with rituximab for a patient with p-ANCA glomerulonephritis, alveolar bleeding and multiple relapses during haemodialysis" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M.A. Azancot, I. Agraz Pamplona, J. Fort Ros, A. Marín Valencia, I. Gil Carballeira, J. Camps Domenech" "autores" => array:6 [ 0 => array:2 [ "Iniciales" => "M.A." "apellidos" => "Azancot" ] 1 => array:2 [ "Iniciales" => "I." "apellidos" => "Agraz Pamplona" ] 2 => array:2 [ "Iniciales" => "J." "apellidos" => "Fort Ros" ] 3 => array:2 [ "Iniciales" => "A." "apellidos" => "Marín Valencia" ] 4 => array:2 [ "Iniciales" => "I." "apellidos" => "Gil Carballeira" ] 5 => array:2 [ "Iniciales" => "J." "apellidos" => "Camps Domenech" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "X2013251410050798" "doi" => "10.3265/Nefrologia.pre2010.Aug.10535" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X2013251410050798?idApp=UINPBA000064" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X0211699510050790?idApp=UINPBA000064" "url" => "/02116995/0000003000000006/v0_201502091423/X0211699510050790/v0_201502091424/es/main.assets" ] ] "itemSiguiente" => array:17 [ "pii" => "X201325141005078X" "issn" => "20132514" "doi" => "10.3265/Nefrologia.pre2010.Oct.10679" "estado" => "S300" "fechaPublicacion" => "2010-11-01" "documento" => "article" "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/" "subdocumento" => "fla" "cita" => "Nefrologia (English Version). 2010;30:712-3" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 4722 "formatos" => array:3 [ "EPUB" => 304 "HTML" => 4001 "PDF" => 417 ] ] "en" => array:8 [ "idiomaDefecto" => true "titulo" => "Kidney failure and diabetis. Diagnostic inertia?" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "712" "paginaFinal" => "713" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Insuficiencia renal y diabetes. ¿Inercia diagnóstica?" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig1" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "10679_108_11451_en_10679_18107_9922_es_10679_108_9922_es_5922_f1.jpg" "Alto" => 695 "Ancho" => 1042 "Tamanyo" => 564078 ] ] "descripcion" => array:1 [ "en" => "E.M: Postinfectious GN. Presence of subepithelial electron-dense deposits (humps)" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "R. Blanco García, J.J. Bravo López, A. Pérez, M. Moreiras Plaza" "autores" => array:4 [ 0 => array:2 [ "Iniciales" => "R." "apellidos" => "Blanco García" ] 1 => array:2 [ "Iniciales" => "J.J." "apellidos" => "Bravo López" ] 2 => array:2 [ "Iniciales" => "A." "apellidos" => "Pérez" ] 3 => array:2 [ "Iniciales" => "M." "apellidos" => "Moreiras Plaza" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "X0211699510050782" "doi" => "10.3265/Nefrologia.pre2010.Oct.10679" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X0211699510050782?idApp=UINPBA000064" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X201325141005078X?idApp=UINPBA000064" "url" => "/20132514/0000003000000006/v0_201502091649/X201325141005078X/v0_201502091649/en/main.assets" ] "itemAnterior" => array:17 [ "pii" => "X2013251410050802" "issn" => "20132514" "doi" => "10.3265/Nefrologia.pre2010.Aug.10563" "estado" => "S300" "fechaPublicacion" => "2010-11-01" "documento" => "article" "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/" "subdocumento" => "fla" "cita" => "Nefrologia (English Version). 2010;30:709-10" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 4378 "formatos" => array:3 [ "EPUB" => 289 "HTML" => 3673 "PDF" => 416 ] ] "en" => array:7 [ "idiomaDefecto" => true "titulo" => "Coexistence of anti-GBM antibodies and MPO-ANCA in a patient with systemic vasculitis and crescentic glomerulonephritis" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "709" "paginaFinal" => "710" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig1" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "10563_108_7732_en_10563_f1.jpg" "Alto" => 257 "Ancho" => 333 "Tamanyo" => 27773 ] ] "descripcion" => array:1 [ "en" => "Kidney biopsy showing crescentic glomerulonephritis (Masson trichrome, x100)." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "P. Fernandes, J.A. Lopes, L. Correia, S. Gonçalves, S. Jorge" "autores" => array:5 [ 0 => array:2 [ "Iniciales" => "P." "apellidos" => "Fernandes" ] 1 => array:2 [ "Iniciales" => "J.A." "apellidos" => "Lopes" ] 2 => array:2 [ "Iniciales" => "L." "apellidos" => "Correia" ] 3 => array:2 [ "Iniciales" => "S." "apellidos" => "Gonçalves" ] 4 => array:2 [ "Iniciales" => "S." "apellidos" => "Jorge" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "X0211699510050805" "doi" => "10.3265/Nefrologia.pre2010.Aug.10563" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X0211699510050805?idApp=UINPBA000064" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X2013251410050802?idApp=UINPBA000064" "url" => "/20132514/0000003000000006/v0_201502091649/X2013251410050802/v0_201502091649/en/main.assets" ] "en" => array:9 [ "idiomaDefecto" => true "titulo" => "Treatment with rituximab for a patient with p-ANCA glomerulonephritis, alveolar bleeding and multiple relapses during haemodialysis" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "710" "paginaFinal" => "712" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "M.A. Azancot, I. Agraz Pamplona, J. Fort Ros, A. Marín Valencia, I. Gil Carballeira, J. Camps Domenech" "autores" => array:6 [ 0 => array:3 [ "Iniciales" => "M.A." "apellidos" => "Azancot" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 1 => array:4 [ "Iniciales" => "I." "apellidos" => "Agraz Pamplona" "email" => array:1 [ 0 => "iagraz@vhebron.net" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] 2 => array:3 [ "Iniciales" => "J." "apellidos" => "Fort Ros" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 3 => array:3 [ "Iniciales" => "A." "apellidos" => "Marín Valencia" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 4 => array:3 [ "Iniciales" => "I." "apellidos" => "Gil Carballeira" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 5 => array:3 [ "Iniciales" => "J." "apellidos" => "Camps Domenech" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Sección de Nefrología, Hospital Vall d'Hebron, Barcelona, " "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] 1 => array:3 [ "entidad" => "Sección de Nefrología, Hospital Vall d'Hebron Barcelona, " "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Tratamiento con rituximab en un paciente con glomerulonefritis p-ANCA, hemorragia alveolar y múltiples recidivas en hemodiálisis" ] ] "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">To the Editor,</span></p><p class="elsevierStylePara">The treatment of vasculitis associated with ANCA is still a topic of interest. Corticosteroids and cyclophosphamide are still the cornerstone in the treatment of vasculitis associated with ANCA. We must also point out the use of rituximab, a chimeric anti-CD20 antibody which has already been studied in several series of patients and which seems to have a beneficial effect on refractory patients or those with intolerance to the first-line therapy. It has also been used with other types of primary glomerulonephritis.</p><p class="elsevierStylePara">Several outbreaks seem to appear during the course of vasculitis associated with ANCA. In patients with an established chronic disease on dialysis or kidney transplant recipients, relapse from the baseline disease is usually unlikely, but not impossible.</p><p class="elsevierStylePara">We present the case of a patient diagnosed with vasculitis associated with ANCA with lung and kidney disease being treated with renal replacement therapy with haemodialysis. He suffered multiple outbreaks despite treatment with cyclophosphamide, corticosteroids and mycophenalate sodium. However, on beginning treatment with rituximab, he achieved full remission from the disease and ANCA levels returned to normal.</p><p class="elsevierStylePara">A male of 65 years of age, ex-smoker, diabetic was admitted to hospital in 2005 due to minor haemoptysis, oedemas on lower limbs, polyneuropathy, deterioration in renal function, and creatinine levels of 6 mg/dl. He was found to have severe anaemia together with impaired renal function, proteinuria of 1.5 g/day, haematuria with dysmorphic red blood cells; he was positive for mpo-ANCA with a titre of 68.34 U/ml. A kidney biopsy was performed showing extracapillary glomerulonephritis with fibrinoid necrosis and crescent formations with negative immunofluorescence. In view of the diagnosis of pauci-immune extracapillary glomerulonephritis with pulmonary involvement, treatment was begun with 3 bolus of methylprednisolone at 1 g/day and monthly cyclophosphamide bolus. The patient was discharged with creatinine level of 2.9 mg/dl, and continued the treatment with monthly bolus cyclophosphamide and corticosteroids.</p><p class="elsevierStylePara">A year after the diagnosis, in 2006, still in treatment with cyclophosphamide and corticosteroids, he had a new outbreak of vasculitis with a deterioration in renal function (Cr of 10.4 mg/dl), an increase in proteinuria and p-ANCA levels (188 U/l), with no evidence of alveolar bleeding. He was treated with methylprednisolone bolus. In view of the severity of the outbreak and the lack of renal function improvement, he was given renal replacement therapy with haemodialysis.</p><p class="elsevierStylePara">During the follow-up, the patient was diagnosed with bronchiectasis, and was admitted on several occasions with superinfections of the lung.</p><p class="elsevierStylePara">In 2007, a year after the onset of haemodialysis and in remission from the disease, he was re-admitted with a new outbreak of vasculitis with an episode of haemoptysis, muscle pain, asthenia, and worsening of the anaemia. ANCA levels were 100 U/l. He was treated with corticosteroids and i.v. cyclophosphamide, with a remission in the outbreak. Six months later, still in treatment with cyclophosphamide, he had a new outbreak characterized by fever, asthenia, haemoptysis and ANCA of 193 U/l. Treatment was begun with corticosteroids and cyclophosphamide, and mycophenolate was added as a maintenance therapy but was badly tolerated due to a digestive disorder and was abandoned.</p><p class="elsevierStylePara">In view of the patient’s history of outbreaks of vasculitis despite the standard immunosuppressor treatment with cyclophosphamide, and the fact that he was undergoing renal replacement therapy with haemodialysis, it was decided to begin treatment with 4 doses (375 mg/m<span class="elsevierStyleSup">2</span>) of rituximab.</p><p class="elsevierStylePara">Later, the patient continued treatment with 4 bolus of cyclophosphamide per month, remaining in remission and with ANCA negativisation 21 months after beginning treatment with rituximab, without any secondary complications to date.</p><p class="elsevierStylePara">The pathogenesis of glomerulonephritis associated with ANCA is not totally clear. ANCA have been related with the pathogenesis of vasculitis, although the levels of ANCA in circulation do not always correlate with the level of activity of the disease. The generation of ANCA is determined by the activation of autoreactive B lymphocytes through the chronic stimulation of T lymphocytes, which explains the relapsing nature of the disease. Furthermore, ANCA produce the liberation of free radicals and proteolytic enzymes which leads to damage of the vascular endothelium in adjacent tissues.<span class="elsevierStyleSup">1</span> </p><p class="elsevierStylePara">Immunosuppressor treatment of the outbreaks in patients on dialysis does not differ from the normal treatment for patients with a generalised disease. Regarding the maintenance therapy, various options have been attempted to reduce the toxicity associated with cyclophosphamide, such as azathioprine, mycophenolate mofetil, and leflunomide.<span class="elsevierStyleSup">2</span></p><p class="elsevierStylePara">In refractory cases, rituximab has been shown to be effective in achieveing remission from the disease in several series of patients. Rituximab is a chimeric anti-CD20 antibody which depletes B lymphocytes, so it has been proposed as a rescue therapy in refractory disease, as the aetiopathogenetic importance of B cells in the generation of ANCA is well known.<span class="elsevierStyleSup">3</span></p><p class="elsevierStylePara">As we have mentioned above, relapse of vasculitis is relatively uncommon in patients on haemodialysis, and it is even rarer to find patients such as ours with multiple relapses in spite receiving standard immunosuppressor therapy and haemodialysis.</p><p class="elsevierStylePara">Little experience has been acquired into the use of rituximab as a rescue therapy in haemodialysis patients. However, reviewing the bibliography, rituximab treatment was assayed in a patient with a history of terminal chronic disease on haemodialysis as a lymphoma B cell treatment, showing that therapeutic levels of the drug remain in the blood despite haemodialysis, so it is not necessary to adjust the treatment doses.<span class="elsevierStyleSup">4</span> Another patient with non-Hodgkin lymphoma requiring haemodialysis was treated with rituximab with no evidence of an increase in side effects.<span class="elsevierStyleSup">5</span></p><p class="elsevierStylePara">In our case, treatment began with 4 doses of rituximab accompanied with a monthly bolus of cyclophosphamide, with which remission from the vasculitis outbreaks was achieved together with the reduction and later negativisation of the levels of ANCA. This suggests that rituximab may be an effective drug as a rescue therapy in patients on chronic haemodialysis with a vasculitis relapse.</p>" "tienePdf" => false "bibliografia" => array:2 [ "titulo" => "Bibliography" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Csernok E, Ai M, Gross WL, et al. Wegener autoantigen induces maturation of dendritis cells and licences them for Th1 priming via the protease - activated receptor-2 pathway. Blood 2006;107(11):4400-8." "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 1 => array:3 [ "identificador" => "bib2" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Jayne DR, Rasmussen N, Andrassy K, et al. A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med 2003;349(1):36-44. <a href="http://www.ncbi.nlm.nih.gov/pubmed/12840090" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 2 => array:3 [ "identificador" => "bib3" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Wong C. Rituximab in refractory antineutrophil cytoplasmic antibody-associated vasculitis: what is the current evidence?. NDT 2007;22:32-6. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17056639" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 3 => array:3 [ "identificador" => "bib4" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Jillella AP, Dainer PM, Kallab AM, Ustun C. Treatment of a patient with end-stage renal disease with Rituximab: pharmacokinetic evaluation suggest Rituximab is not eliminated by hemodialisis. Am J Hematol 2002;71(3):219-22. <a href="http://www.ncbi.nlm.nih.gov/pubmed/12410580" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 4 => array:3 [ "identificador" => "bib5" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Feldman G, Nattermann J, Gerhart T, Nähle CP, Spengler U, Woitas R. Partial remission of a newly diagnosed diffuse large B-cell Non Hodgkin's lymphoma in a hemodialysis patient after administration of inmuno-chemotherapy with Rituximab-CHOP. Int J Lab Hematol 2007;29(6):469-73. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17988304" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/20132514/0000003000000006/v0_201502091649/X2013251410050798/v0_201502091649/en/main.assets" "Apartado" => array:4 [ "identificador" => "35437" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor - Brief Case Reports" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X2013251410050798?idApp=UINPBA000064" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 6 | 0 | 6 |
| 2024 October | 51 | 0 | 51 |
| 2024 September | 49 | 0 | 49 |
| 2024 August | 52 | 0 | 52 |
| 2024 July | 34 | 0 | 34 |
| 2024 June | 57 | 0 | 57 |
| 2024 May | 63 | 0 | 63 |
| 2024 April | 52 | 0 | 52 |
| 2024 March | 54 | 4 | 58 |
| 2024 February | 28 | 11 | 39 |
| 2024 January | 42 | 11 | 53 |
| 2023 December | 31 | 5 | 36 |
| 2023 November | 56 | 9 | 65 |
| 2023 October | 41 | 14 | 55 |
| 2023 September | 37 | 13 | 50 |
| 2023 August | 54 | 7 | 61 |
| 2023 July | 47 | 11 | 58 |
| 2023 June | 48 | 9 | 57 |
| 2023 May | 51 | 12 | 63 |
| 2023 April | 28 | 1 | 29 |
| 2023 March | 45 | 0 | 45 |
| 2023 February | 41 | 3 | 44 |
| 2023 January | 56 | 2 | 58 |
| 2022 December | 64 | 2 | 66 |
| 2022 November | 62 | 3 | 65 |
| 2022 October | 55 | 2 | 57 |
| 2022 September | 50 | 4 | 54 |
| 2022 August | 49 | 3 | 52 |
| 2022 July | 38 | 0 | 38 |
| 2022 June | 44 | 2 | 46 |
| 2022 May | 86 | 2 | 88 |
| 2022 April | 52 | 1 | 53 |
| 2022 March | 51 | 2 | 53 |
| 2022 February | 75 | 1 | 76 |
| 2022 January | 98 | 1 | 99 |
| 2021 December | 56 | 3 | 59 |
| 2021 November | 69 | 1 | 70 |
| 2021 October | 92 | 2 | 94 |
| 2021 September | 64 | 5 | 69 |
| 2021 August | 49 | 1 | 50 |
| 2021 July | 55 | 3 | 58 |
| 2021 June | 30 | 2 | 32 |
| 2021 May | 41 | 0 | 41 |
| 2021 April | 139 | 19 | 158 |
| 2021 March | 71 | 9 | 80 |
| 2021 February | 71 | 9 | 80 |
| 2021 January | 39 | 7 | 46 |
| 2020 December | 41 | 2 | 43 |
| 2020 November | 47 | 5 | 52 |
| 2020 October | 42 | 3 | 45 |
| 2020 September | 27 | 1 | 28 |
| 2020 August | 43 | 5 | 48 |
| 2020 July | 36 | 5 | 41 |
| 2020 June | 33 | 2 | 35 |
| 2020 May | 32 | 6 | 38 |
| 2020 April | 33 | 10 | 43 |
| 2020 March | 38 | 13 | 51 |
| 2020 February | 43 | 13 | 56 |
| 2020 January | 48 | 7 | 55 |
| 2019 December | 43 | 8 | 51 |
| 2019 November | 44 | 5 | 49 |
| 2019 October | 29 | 2 | 31 |
| 2019 September | 27 | 14 | 41 |
| 2019 August | 35 | 0 | 35 |
| 2019 July | 40 | 17 | 57 |
| 2019 June | 46 | 14 | 60 |
| 2019 May | 35 | 3 | 38 |
| 2019 April | 69 | 17 | 86 |
| 2019 March | 41 | 12 | 53 |
| 2019 February | 13 | 6 | 19 |
| 2019 January | 31 | 8 | 39 |
| 2018 December | 86 | 24 | 110 |
| 2018 November | 112 | 11 | 123 |
| 2018 October | 82 | 19 | 101 |
| 2018 September | 49 | 10 | 59 |
| 2018 August | 30 | 13 | 43 |
| 2018 July | 40 | 11 | 51 |
| 2018 June | 39 | 14 | 53 |
| 2018 May | 55 | 12 | 67 |
| 2018 April | 40 | 9 | 49 |
| 2018 March | 39 | 8 | 47 |
| 2018 February | 40 | 7 | 47 |
| 2018 January | 34 | 9 | 43 |
| 2017 December | 40 | 8 | 48 |
| 2017 November | 37 | 10 | 47 |
| 2017 October | 32 | 8 | 40 |
| 2017 September | 26 | 10 | 36 |
| 2017 August | 40 | 9 | 49 |
| 2017 July | 32 | 11 | 43 |
| 2017 June | 40 | 15 | 55 |
| 2017 May | 47 | 6 | 53 |
| 2017 April | 32 | 5 | 37 |
| 2017 March | 37 | 6 | 43 |
| 2017 February | 30 | 4 | 34 |
| 2017 January | 19 | 10 | 29 |
| 2016 December | 65 | 7 | 72 |
| 2016 November | 63 | 7 | 70 |
| 2016 October | 106 | 13 | 119 |
| 2016 September | 149 | 3 | 152 |
| 2016 August | 195 | 0 | 195 |
| 2016 July | 161 | 0 | 161 |
| 2016 June | 106 | 0 | 106 |
| 2016 May | 118 | 0 | 118 |
| 2016 April | 98 | 0 | 98 |
| 2016 March | 63 | 0 | 63 |
| 2016 February | 103 | 0 | 103 |
| 2016 January | 103 | 0 | 103 |
| 2015 December | 111 | 0 | 111 |
| 2015 November | 68 | 0 | 68 |
| 2015 October | 63 | 0 | 63 |
| 2015 September | 59 | 0 | 59 |
| 2015 August | 72 | 0 | 72 |
| 2015 July | 72 | 0 | 72 |
| 2015 June | 37 | 0 | 37 |
| 2015 May | 61 | 0 | 61 |
| 2015 April | 5 | 0 | 5 |
Show all
