Rhabdomyolysis due to enzyme deficiency in muscles
Rabdomiolisis por déficits enzimáticos musculares
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"80" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "Remedios Toledo Rojas, Verónica López Jiménez, Guillermo Martín Reyes, Alvaro Torres Rueda, Miguel Angel Frutos Sanz" "autores" => array:5 [ 0 => array:3 [ "nombre" => "Remedios" "apellidos" => "Toledo Rojas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 1 => array:3 [ "nombre" => "Verónica" "apellidos" => "López Jiménez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 2 => array:3 [ "nombre" => "Guillermo" "apellidos" => "Martín Reyes" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 3 => array:3 [ "nombre" => "Alvaro" "apellidos" => "Torres Rueda" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 4 => 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class="elsevierStylePara"><span class="elsevierStyleBold">INTRODUCTION</span></p><p class="elsevierStylePara">The Metabolic Myopathies (MM) comprise a heterogeneous group of genetic disorders that compromise the glycogen synthase pathway, lipids, purines or the mitochondrial metabolism resulting in muscle tissue unable to produce the necessary energy. Even though clinical symptoms vary according to the type of problem, it is also verified exercise intolerance and myalgia besides exertional rhabdomyolysis. In general, these are not usually the cause of Acute Renal Failure (ARF), but frequent episodes of rhabdomyolysis during a childhood with moderate physical activity should raise suspicion. To confirm, it is required to employ molecular biology techniques to determine the effect from the enzyme.</p><p class="elsevierStylePara">Two cases of myopathy due to enzyme deficiency that resulted in ARF due to rhabdomyolysis are presented.</p><p class="elsevierStylePara"><span class="elsevierStyleBold">CASE 1</span></p><p class="elsevierStylePara">A 30-year-old man, who at the age of 14 suffered from episodes of acute myalgia and from dark urine due to prolonged physical exercise (walking 6-7 kilometres.) No family member showed similar episodes.</p><p class="elsevierStylePara">After four years of no symptoms, one day after a basketball game he began to have general myalgies and dark urine. In order to reduce muscle pain, he initiated a treatment with ibuprofen (1.200 mg/d during 3 days.) In the following days it was verified nausea, vomit and a volume drop of diuresis, reasons why he visited our centre.</p><p class="elsevierStylePara">The patient was found to be hypertensive (160/90 mmHg), without fever, in a good general condition and slightly dehydrated. The analytical study revealed leukocytes (13.400 x103/μl) with neutrophilia (85%), haemoglobin 14.5g/dl, plasmatic creatinine 13,1mg/dl, urea 233mg/dl, sodium 127mEq/l, potassium 5.4mEq/l, calcium 8.1mg/dl, albumin 2.5g/dl, LDH 2.649U/L, CPK 2.266U/L, uric acid 9mg/dl, phosphorus 5.2mg/dl, GOT 83U/L and GPT 264U/L. Urine: creatinine 87mg/dl, sodium 48meq/l, haemoglobin (3+), sediment 15-20 haematids/field.</p><p class="elsevierStylePara">He was treated by recovering the loss of volume and through urine alcalinization. However, the renal function continued to get worse. On the 4th day of treatment and after two sessions of haemodialysis, he began to recover his renal function which returned to normal after three weeks. The myalgia improved progressively until it disappeared.</p><p class="elsevierStylePara">With the clinical possibility of a MM, given the recurrent nature of the picture and its relation with physical exercise, once it was recivered ARF the patient underwent a muscle biopsy that gave a normal histology. Nevertheless, by determining the enzyme activity of Carnitine Palmitoyl transferase (CPT) in the muscles through isotope exchange – performed in the hospital’s research centre on the 12th of October, in Madrid – it was detected a reduced activity with a result of 0.07nmol/min<span class="elsevierStyleSup">-1</span>/mg<span class="elsevierStyleSup">-1</span> NPC, with the lowest reference limit being 21 nmol/min<span class="elsevierStyleSup">-1</span>/mg<span class="elsevierStyleSup">-1</span> NPC. It was diagnosed a deficiency of CPT and the patient was told to avoid prolonged physical exertions and to eat frequently with a diet low on calories and high on carbohydrates.</p><p class="elsevierStylePara"><span class="elsevierStyleBold">CASE 2</span></p><p class="elsevierStylePara">A 39-year-old man, diagnosed 20 years earlier with McArdle’s Disease through muscle biopsy, performed after showing episodes of acute myalgia related with physical exertions during childhood. A study of the family history revealed the same affliction in four of his 11 brothers, in who the problem seemed to have no clinical significance.</p><p class="elsevierStylePara">After spending several days using a transcutaneous electrical stimulation device with the purpose of increasing muscle mass in the abdominal wall, he began to experience strength loss, myalgia, dark urine and decrease in diuresis. The patient visited our centre one week later. He was found to be normotensive, without fever, presenting serious oedemas in lower limbs and with oliguria.</p><p class="elsevierStylePara">In the analytical study, the hemogram was normal, plasmatic creatinine 12,4mg/dl, urea 128mg/dl, sodium 134meq/l, potassium 5.5meq/l, calcium 6.9mg/dl, albumin 3g/dl, LDH 406U/L, CK 15.507U/L, uric acid 5.8mg/dl, phosphorus 5.4mg/dl, GOT 88U/L and GPT 148U/L. A radiography of the chest revealed bilateral pleural effusion and interstitial oedema.</p><p class="elsevierStylePara">He required treatment with nine sessions of haemodialysis, achieving a negative hydric balance of more than 18kg. After two weeks of treatment, he began to recuperate diuresis and slowly decrease the plasmatic creatinine until it became normal. There was also a complete recuperation of muscle strength. The patient was advised to avoid physical exercise and increase his diet's protein level.</p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara">In 1941 it was performed the first detailed description of rhabdomyolysis.<span class="elsevierStyleSup">1</span> Since then, numerous cases report has been published and it has been known a growing list of possible etiologies<span class="elsevierStyleSup">2</span> (table 1.)</p><p class="elsevierStylePara">In the 50s a group of patients was diagnosed with recurrent episodes of rhabdomyolysis, often starting in childhood and with a family history of myoglobinuria. After 1970, hereditary enzyme abnormalities related with these recurrent cases began to be verified.</p><p class="elsevierStylePara">MM create a heterogenous group of uncommon diseases where the energetic metabolism of the muscles is changed, resulting in a skeletal muscle dysfunction. These are ordered according to the way they affect the metabolic pathway of glucogen, lipids, purines or mitochondrial metabolism<span class="elsevierStyleSup">3</span> (table 2.) Even though it has not been established a precise mechanism for muscle necrosis, it is likely that the insufficient production of energy during exercise may lead to a depletion of ATP that can jeopardize muscle cells.<span class="elsevierStyleSup">4</span></p><p class="elsevierStylePara">In the first case, the patient was diagnosed with CPT deficiency, a rare abnormality of the lipid metabolism related to autosomal recessive inheritance (AR.) Even though it represents a small percentage of rhabdomyolysis cases, it is the most common MM.</p><p class="elsevierStylePara">The enzyme deficiency prevents the transportation of fatty acids to the mitochondrion for beta oxidation and later ATP synthese. When performing a prolonged physical exercise (at least one hour) the energy produced through this pathway is necessary after the depletion of glycogen reserves and the resulting muscle injury include myalgia and in some cases myoglobin, with possible complication of ARF. Known triggering effects include fasting, fever and anti-inflammatory drugs.<span class="elsevierStyleSup">5</span> The patient suffered myoglobinuria after performing prolonged physical exertions. Furthermore, the described episode was associated with the use of ibuprofen, which can prompt the development of ARF.</p><p class="elsevierStylePara">Mc Ardle’s the most common disorder of muscle carbohydrate metabolism and the second most common MM that causes rhabdomyolysis." AR inheritance is also caused by mutations in the genetic code of myophosphorylase enzyme. Its deficiency makes the glycogen’s metabolism difficult, which comprises the main source of muscle energy specially when performing short and intense exercises. Patients with McArdle’s disease present intolerance to shortterm exercise and cramps or muscle weakness especially as in the case of our patient when he was subjected to short and frequent periods of physical exercise through the use of an electrostimulator. Up to half the cases of McArdle’s disease begin with episodes of rhabdomyolysis and half of these complicate with ARF.<span class="elsevierStyleSup">2</span></p><p class="elsevierStylePara">A clinical analysis is essential for the diagnosis of MM. Regarding the inheritance of AR, in many cases it is verified that family history is not a determinant factor. However, it is very important for rhabdomyolysis to be frequent and begin during childhood. The clinical characteristics of the main MM useful for a differential diagnosis is summarised in table 2. The definitive diagnosis requires a muscle biopsy in order to identify the enzyme disorder through molecular biology techniques.</p><p class="elsevierStylePara">Currently, there is no cure. Being careful with hygiene and diet will also help to prevent myoglobinuria.<span class="elsevierStyleSup">2</span> It is necessary to control physical activity. Concerning CPT deficiency, excercises should be short-time and avoided in case of fasting or infections. It is recommended to have a frequent meals with a low fat and high carbohydrate diet, which will be the main source of energy in these cases. The daily consumption of medium chain triglycerides can be beneficial, as verified in some cases.<span class="elsevierStyleSup">6</span></p><p class="elsevierStylePara">As for myophosphorylase deficiency, besides limiting physical exercise, it is advised to increase the diet’s protein level, since it improves resistance and muscle operation in most cases.<span class="elsevierStyleSup">7</span> On the other hand, it was verified in a controlled study with 12 patients that sucrose intake before exercise improves considerably its tolerance. The sucrose is quickly converted in glucose and fructose, which the muscle will use to obtain energy due to the inability to metabolize muscle glycogen. Although useful, it is a measure that should be taken with caution due to the high level of calories, which can result in an excessive weight gain.<span class="elsevierStyleSup">8</span> Vitamin B6 supplements were also found to be beneficial in case of McArdle’s disease, but needs to be verified by controlled studies.<span class="elsevierStyleSup">9</span></p><p class="elsevierStylePara">Perhaps in the near future a specific treatment will be available by enzyme replacement or a genetic treatment that will allow to improve effectively the tolerance to exercise, preventing episodes of rhabdomyolysis.</p><p class="elsevierStylePara"><a href="grande/23418078_t1_p79.jpg" class="elsevierStyleCrossRefs"><img src="23418078_t1_p79.jpg" alt="Causes for rhabdomyolysis"></img></a></p><p class="elsevierStylePara">Table 1. Causes for rhabdomyolysis</p><p class="elsevierStylePara"><a href="grande/23418078_t2_p80.jpg" class="elsevierStyleCrossRefs"><img src="23418078_t2_p80.jpg" alt="Metabolic myopathies"></img></a></p><p class="elsevierStylePara">Table 2. Metabolic myopathies</p>" "pdfFichero" => "P-E-S-A234-EN.pdf" "tienePdf" => true "PalabrasClave" => array:2 [ "es" => array:4 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec440399" "palabras" => array:1 [ 0 => "Déficit de miofosforilasa" ] ] 1 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec440401" "palabras" => array:1 [ 0 => "Déficit de carnitina palmitoil-transferasa" ] ] 2 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec440403" "palabras" => array:1 [ 0 => "Miopatía" ] ] 3 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec440405" "palabras" => array:1 [ 0 => "Rabdomiólisis" ] ] ] "en" => array:4 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec440400" "palabras" => array:1 [ 0 => "Myophosphorylase deficiency" ] ] 1 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec440402" "palabras" => array:1 [ 0 => "Carnitine palmitoyl transferase deficiency" ] ] 2 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec440404" "palabras" => array:1 [ 0 => "Myopathy" ] ] 3 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec440406" "palabras" => array:1 [ 0 => "Rhabdomyolysis" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "es" => array:1 [ "resumen" => "<p class="elsevierStylePara">La rabdomiólisis es un síndrome producido por la lesión del músculo estriado con liberación al torrente sanguíneo de gran cantidad de productos intracelulares. Es frecuente el desarrollo de fracaso renal agudo que, además, constituye el principal factor de morbimortalidad en estos pacientes. Entre las causas más frecuentes destacan los traumatismos, la compresión muscular o la realización de ejercicio físico intenso. Son casos que se reconocen fácilmente al realizar una adecuada historia clínica. Sin embargo, en ausencia de un desencadenante claro, el diagnóstico es difícil y suele requerir un alto grado de sospecha. Deben investigarse consumo de drogas y fármacos, infecciones, trastornos electrolíticos y determinados defectos enzimáticos en los que el músculo es incapaz de utilizar la energía disponible. Presentamos dos casos de fracaso renal agudo debido a rabdomiólisis por miopatías metabólicas, secundarios a déficit de carnitina-palmitoil-transferasa en un caso y de miofosforilasa en el otro. Se revisa esta enfermedad insistiendo en las formas de presentación y medidas preventivas.</p>" ] "en" => array:1 [ "resumen" => "<p class="elsevierStylePara">Rhabdomyolysis is a syndrome characterized by injure of skeletal muscle with the release of intracellular constituents into the circulation. Acute renal failure is a common complication and is the leading cause of morbidity and mortality in these patients. The most common aetiology is traumatisms, muscle compressions and extreme exertions. Most commonly, the cause of rhabdomyolysis is evident from the careful clinical history. Nevertheless, when the precipitant is not obvious the diagnosis is difficult and a raised clinical suspicion is required. We should investigate used medication or drugs, infections, electrolyte abnormalities and a number of inherited enzyme deficiencies, in which cases the muscle is unable to use available energy. We report two clinical cases of acute renal failure due to rhabdomyolysis by metabolic myopathies due to a carnitine palmitoyltransferase deficiency on the one hand and by myophosphorylase deficiency on the other. We describe their clinical features and progress.</p>" ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "fig1" "etiqueta" => "Tab. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "23418078_t1_p79.jpg" "Alto" => 846 "Ancho" => 399 "Tamanyo" => 46199 ] ] "descripcion" => array:1 [ "en" => "Causes for rhabdomyolysis" ] ] 1 => array:8 [ "identificador" => "fig2" "etiqueta" => "Tab. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "23418078_t2_p80.jpg" "Alto" => 764 "Ancho" => 824 "Tamanyo" => 102140 ] ] "descripcion" => array:1 [ "en" => "Metabolic myopathies" ] ] ] "bibliografia" => array:2 [ "titulo" => "Bibliography" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:9 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Bywaters EGL, Beall D. Crush injuries with impairment of renal function. Br Med J 1941;1:427-32. <a href="http://www.ncbi.nlm.nih.gov/pubmed/20783577" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 1 => array:3 [ "identificador" => "bib2" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Bagley WH, Yang H, Shah KH. Rhabdomyiolysis. Intern Emerg Med 2007;2:210-8. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17909702" 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" => "Walsh R. Metabolic myopathies. CONTINUUM Lifelong Learn. Neurol 2006;12:76-120." "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 3 => array:3 [ "identificador" => "bib4" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Wortmann RL. Metabolic and mitochondrial myopathies. Curr Opin Reumatol 1999;11:462-7." "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 4 => array:3 [ "identificador" => "bib5" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Ross NS, Hoppel CL. Partial muscle carnitin palmitoyl transferase- A deficiency. Rhabdomiolisis associated with transiently decreased muscle carnitin content after ibuprofen therapy. JAMA 1987;257:62-5. <a href="http://www.ncbi.nlm.nih.gov/pubmed/3783904" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 5 => array:3 [ "identificador" => "bib6" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "CwikV. Disoders of lipid metabolism in skeletal muscle. Neurol Clin 2000;18:167-84. <a href="http://www.ncbi.nlm.nih.gov/pubmed/10658173" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:1 [ "itemHostRev" => array:3 [ "pii" => "S0735109706028889" "estado" => "S300" "issn" => "07351097" ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib7" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Jensen K, Jakobsen J, Thomsen C, Heriksen O. Improved energy kinetics following high protein diet in McArdle¿s syndrome: a 31P magnetic resonance spectroscopy study. Acta Neurol Scand 1990;81:499-503. <a href="http://www.ncbi.nlm.nih.gov/pubmed/2220306" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 7 => array:3 [ "identificador" => "bib8" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Vissing J, Haller RG. The effect of oral sucrose on exercise tolerance in patients with McArdle¿s disease. N Engl J Med 2003;349:2503-09." "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 8 => array:3 [ "identificador" => "bib9" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Phoenix J, Hopkins P, Bartram C, Beynon RJ, Quinlivan RCM, Edwards RHT. Effect of vitamin B6 supplementation in McArdle¿s disease: a strategic case study. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 16 | 10 | 26 |
| 2024 October | 107 | 28 | 135 |
| 2024 September | 124 | 46 | 170 |
| 2024 August | 125 | 64 | 189 |
| 2024 July | 96 | 34 | 130 |
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| 2024 April | 80 | 47 | 127 |
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| 2024 January | 54 | 39 | 93 |
| 2023 December | 61 | 25 | 86 |
| 2023 November | 77 | 38 | 115 |
| 2023 October | 79 | 27 | 106 |
| 2023 September | 116 | 34 | 150 |
| 2023 August | 115 | 32 | 147 |
| 2023 July | 147 | 50 | 197 |
| 2023 June | 105 | 32 | 137 |
| 2023 May | 151 | 42 | 193 |
| 2023 April | 58 | 37 | 95 |
| 2023 March | 99 | 30 | 129 |
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| 2023 January | 77 | 35 | 112 |
| 2022 December | 80 | 40 | 120 |
| 2022 November | 77 | 51 | 128 |
| 2022 October | 99 | 48 | 147 |
| 2022 September | 76 | 52 | 128 |
| 2022 August | 104 | 59 | 163 |
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| 2022 June | 63 | 39 | 102 |
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| 2022 April | 97 | 51 | 148 |
| 2022 March | 71 | 78 | 149 |
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| 2021 December | 85 | 71 | 156 |
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| 2021 October | 169 | 78 | 247 |
| 2021 September | 82 | 59 | 141 |
| 2021 August | 94 | 47 | 141 |
| 2021 July | 140 | 58 | 198 |
| 2021 June | 76 | 45 | 121 |
| 2021 May | 87 | 33 | 120 |
| 2021 April | 179 | 56 | 235 |
| 2021 March | 108 | 38 | 146 |
| 2021 February | 149 | 49 | 198 |
| 2021 January | 85 | 30 | 115 |
| 2020 December | 98 | 28 | 126 |
| 2020 November | 94 | 22 | 116 |
| 2020 October | 78 | 26 | 104 |
| 2020 September | 85 | 24 | 109 |
| 2020 August | 58 | 13 | 71 |
| 2020 July | 56 | 16 | 72 |
| 2020 June | 76 | 18 | 94 |
| 2020 May | 72 | 24 | 96 |
| 2020 April | 68 | 21 | 89 |
| 2020 March | 71 | 30 | 101 |
| 2020 February | 70 | 28 | 98 |
| 2020 January | 101 | 29 | 130 |
| 2019 December | 77 | 16 | 93 |
| 2019 November | 93 | 17 | 110 |
| 2019 October | 86 | 15 | 101 |
| 2019 September | 110 | 21 | 131 |
| 2019 August | 105 | 26 | 131 |
| 2019 July | 120 | 21 | 141 |
| 2019 June | 73 | 15 | 88 |
| 2019 May | 112 | 28 | 140 |
| 2019 April | 163 | 38 | 201 |
| 2019 March | 105 | 18 | 123 |
| 2019 February | 104 | 13 | 117 |
| 2019 January | 74 | 14 | 88 |
| 2018 December | 146 | 25 | 171 |
| 2018 November | 149 | 13 | 162 |
| 2018 October | 154 | 11 | 165 |
| 2018 September | 127 | 15 | 142 |
| 2018 August | 112 | 18 | 130 |
| 2018 July | 60 | 11 | 71 |
| 2018 June | 60 | 8 | 68 |
| 2018 May | 53 | 9 | 62 |
| 2018 April | 111 | 11 | 122 |
| 2018 March | 58 | 17 | 75 |
| 2018 February | 54 | 5 | 59 |
| 2018 January | 35 | 8 | 43 |
| 2017 December | 61 | 12 | 73 |
| 2017 November | 52 | 11 | 63 |
| 2017 October | 38 | 10 | 48 |
| 2017 September | 67 | 10 | 77 |
| 2017 August | 41 | 6 | 47 |
| 2017 July | 47 | 10 | 57 |
| 2017 June | 49 | 16 | 65 |
| 2017 May | 48 | 11 | 59 |
| 2017 April | 42 | 6 | 48 |
| 2017 March | 37 | 4 | 41 |
| 2017 February | 89 | 5 | 94 |
| 2017 January | 33 | 8 | 41 |
| 2016 December | 55 | 11 | 66 |
| 2016 November | 87 | 21 | 108 |
| 2016 October | 131 | 10 | 141 |
| 2016 September | 194 | 8 | 202 |
| 2016 August | 245 | 7 | 252 |
| 2016 July | 169 | 7 | 176 |
| 2016 June | 127 | 0 | 127 |
| 2016 May | 126 | 0 | 126 |
| 2016 April | 115 | 0 | 115 |
| 2016 March | 104 | 0 | 104 |
| 2016 February | 96 | 0 | 96 |
| 2016 January | 79 | 0 | 79 |
| 2015 December | 130 | 0 | 130 |
| 2015 November | 84 | 0 | 84 |
| 2015 October | 72 | 0 | 72 |
| 2015 September | 76 | 0 | 76 |
| 2015 August | 89 | 0 | 89 |
| 2015 July | 68 | 0 | 68 |
| 2015 June | 103 | 0 | 103 |
| 2015 May | 53 | 0 | 53 |
| 2015 April | 5 | 0 | 5 |
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