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In the event of snakebite during pregnancy, all patients should be transported left lateral decubitus since a maternal death after snakebite has been reported for presumptive supine hypo

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maternal monitoring capabilities Priorities for evaluation and resuscitation should not differ from those established for the patient who is not pregnant As with multiple other critical situ-ations, the best chance for fetal survival is maternal survival [174] Local measures include positive identifi cation of the type of snake and rapid transport to defi nitive medical care There is no universally applicable method to reliably delay the transport of venom from the bite site to the systemic circulation [169] Calming the patient, immobilization, and splinting of the extrem-ity bitten are crucial A loose constriction bandage may be used

to delay spread of the venom by compressing lymphatic vessels

If care is available within 60 minutes, wound incision and suc-tioning are not recommended Unfortunately negative pressure venom extraction devices have shown no benefi t [175] Tourniquets are not recommended as they can contribute to severe tissue destruction [169] Local and supportive measures for poisonous snakebite include careful cleaning of the wound, maintaining the extremity in neutral position, supportive care, potential use of antibiotics, and tetanus prophylaxis [174] Circumferential measurement at several points along the affected limb should be started shortly after the patient ’ s arrival and repeated hourly until progression has ceased [172]

In general indications for antivenom use are: (a) hypotension

or other signs and symptoms of autopharmacological reactions, (b) hemostatic abnormalities or spontaneous systemic bleeding, (c) paralysis, (d) rhabdomyolysis, (e) cardiovascular signs and symptoms, and (f) renal compromise [169] In local envenom-ation, antivenom is indicated if: (a) the species involved is known

to cause local tissue necrosis, (b) there is swelling involving more than half of the bitten limb, (c) there is rapidly progressive swell-ing, and (d) there are bites on fi ngers and/or toes [169] Although there is no universal grading system for snakebites, a I – IV grading scale is clinically useful as a guide to antivenom administration (Table 39.26 )

When considering the use of antivenom, the risk of adverse reaction to its administration must be weighed against the ben-efi ts of reducing venom toxicity In general, antivenom should

USA include the rattlesnakes ( Sistrurus and Crotalus spp.) and the

moccasins snakes: cotton - mouths ( Agkistrodon piscivorus ) and

copperheads ( Agkistrodon contortrix ) Overall, rattlesnakes cause

two - thirds of all bites by identifi ed venomous snakes in the USA

Venom usually is injected into subcutaneous tissue via fangs;

occasionally, intramuscular or intravenous injection can occur

Dry bites (no envenomation) occur in as many as 50% of strikes

Venom generally is composed of several digestive enzymes and

spreading factors, which result in local and systemic injury

The venom may be cytotoxic, hematotoxic, neurotoxic,

rhab-domyolytic, cardiotoxic, nephrotoxic, or may cause an

autoim-mune reaction (complement activation) In general, viper

(Crotalidae spp.) venom is mainly cytotoxic, whereas elapid

venom is mainly neurotoxic, colubrid venom predominantly

hemotoxic, and sea snake venom chiefl y myotoxic [174]

Subdivision of symptoms into local, autopharmacological,

antihemostatic, neurological, muscular, cardiac, and renal effects

help to stage the patient In conjunction with information on

geographical distribution, habitat, and behavior of the snake, the

clinical pattern of symptoms and signs is useful to identify the

culprit of the envenomation [169] Clinically, local effects most

commonly predominate, progressing from pain and edema to

ecchymosis and bullae Hematologic abnormalities, including

benign defi brination with or without thrombocytopenia, may

result, but severe generalized bleeding is uncommon Local or

diffuse myotoxicity may result in complications such as

compart-ment syndrome or rhabdomyolysis Neurotoxins produce

neuro-muscular blockade and nerve conduction Prodromal symptoms

of neurotoxicity (drowsiness, hypersalivation, diaphoresis,

fas-ciculations and circumoral paresthesias) are often followed by

specifi c effects on cranial nerves Progressive respiratory paralysis

is the most serious neurotoxic effect [174] Other rare general

effects include cardiotoxicity, fasciculations, and shock

In the event of snakebite during pregnancy, all patients should

be transported (left lateral decubitus since a maternal death after

snakebite has been reported for presumptive supine hypotensive

syndrome) to a medical care facility with appropriate fetal and

Type of snake No Minor effect Moderate effects Major effects No follow - up

Rattlesnake 3 2 (67%) 0 1 (33%) 0 Nonpoisonous 8 3 (37%) 0 0 5 (63%) Unknown snake 5 3 (60%) 1 (20%) 0 1 (20%) Total 18 10 (56%) 1 (5%) 1 (5%) 6 (34%)

Minor effects are signs or symptoms developing from the exposure but minimally bothersome and generally resolving without residual disability A moderate effect is one that is more pronounced or prolonged than minor effects, usually requiring some form of treatment Major effects are life - threatening signs or symptoms of the exposure that result in signifi cant disability or disfi gurement

(Reproduced by permission from Toxic Exposure Surveillance System (TESS) Exposures in Pregnant Women, 1999 AAPCC 2000.)

Table 39.25 Snake envenomation during

pregnancy by type of snake and maternal effects,

US: 1999

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are unknown, there is evidence that snake venom may cross the placenta affecting the fetus even without evidence of envenom-ation in the mother [178] The effects of venom on the human fetus are unknown Venom exposure during pregnancy may result in teratogenesis, fetal growth retardation, or even mutagen-esis It is also undetermined what effect the different types of venom, the amount and the route of exposure have on the fetus Snake venom has uterotonic properties and fetal wastage during early gestation may be due to intrauterine bleeding, hypoxia and pyrexia [174,179] The absence of short - term and long - term vari-ability in the fetal heart rate is an ominous sign and along the lack

of fetal movements, suggest depression of the CNS of the fetus [174]

We were unable to fi nd any English - language reports of coral snakes (characterized by a black snout and an alternating pattern

of black, yellow, and red) envenomation during pregnancy Coral snakes and sea snakes of the Elapidae family are much less effi cient in injecting venom into large prey; thus, their poor effi -ciency at envenomation, coupled with their relatively small size and shy nature, may play a role in the paucity of information concerning these snake bites during pregnancy Coral snake bites often show little local reaction Systemic effects may be delayed for several hours Because of the neurotoxicity of coral snake venom, coral snake antivenin is usually recommended for its victims Of note, the net effect of these neurotoxins is a curare like syndrome, thus contraindicating the use of magnesium sulfate as a tocolytic if patient develops preterm labor

Occasionally, a victim will present with the bite of a rare, exotic snake Most zoos or poison control centers have specifi c informa-tion on unusual breeds of snakes Timely consultainforma-tion is highly recommended [180]

not be given in the fi eld because of the risk of severe allergic

complications Hypersensitivity reactions are common with

anti-venin use (23 – 56%) [172] Skin testing (which may be unreliable)

and careful monitoring must be available and used when

anti-venin is given

The quality of the antivenoms and its frequency of severe side

effects (nearly 50% of patients treated) makes monitoring and

treatment of side effects an important part of the management of

these patients

Crotalidae polyvalent immune Fab antivenom (CroFab or

FabAV, a sheep - derived antigen - binding fragment) is more

spe-cifi cally tailored for crotalids of North America and is less

aller-genic than equine - derived whole immunoglobulin antivenoms

With pit viper poisoning, antivenin is usually recommended

for grade III or IV bites Crotalidae polyvalent immune Fab

anti-venom effectively controls the effects of enanti-venomation; however,

initial control of coagulopathy is diffi cult to achieve in some

cases, and recurrence or delayed - onset hematotoxicity is not

uncommon [176] Because copperheads carry a lesser potent

venom, their bites usually do not require antivenin

Fasciotomies may be required occasionally but only after

con-fi rmation of the presumptive diagnosis of compartment

syn-drome (pressures above 30 mmHg) and adequate treatment with

antivenom [172]

In their review of snakebites during pregnancy, Dunnihoo et

al [177] reported an overall fetal wastage of 43% and a maternal

mortality of 10% Bleeding diathesis resulted from pit viper

envenomation Possible mechanisms for the fetal losses may be

anoxia associated with shock, bleeding into the placenta and

uterine wall and uterine contractions initiated by the venom

[174] Although the specifi c effects of venom on the human fetus

Table 39.26 Grading of snakebite poisoning

I None 1 inch of edema or erythema,

puncture wounds

II Minimal 1 – 5 inch of edema or erythema

within fi rst 12 h

III Moderate 6 – 12 inch of edema or erythema

within fi rst 12 h

Minimal (nausea, vomiting, paresthesias, metallic taste, and fasciculations)

Platelets < 90 000/ µ L Fibrinogen < 100 mg/dL)

PT > 14 s

CK > 500 – 1000 U/L

IV Severe Rapidly involves the entire part;

potential compartment syndrome

Systemic effects may include shock, diffuse

or life - threatening bleeding, renal failure, respiratory diffi culty, and altered mental status

Platelets < 20 000/ µ L Any abnormal coagulation parameter associated with potentially life - threatening bleeding Rhabdomyolysis Myoglobinuric renal failure

PT, prothrombin time; CK, creatine kinase

(From Wood JT, Hoback WW, Green TW Poisonous snakebites resulting in lack of venom poisoning Va Med Monthly 1955;82:130; and Dunnihoo DR, Rush BM, Wise

RB, Brooks GG, Otterson WN Snake bite poisoning in pregnancy: a review of the literature J Reprod Med 1992;37:653 – 658.)

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ing is a characteristic fi nding associated with black widow enven-omation [172] Other symptoms include: perspiration, nausea, vomiting, diarrhea, sialorrhea, and headache [182] The neuro-muscular manifestation of the envenomation progress over several hours and then subside over 2 – 3 days [185] The evalua-tion of these patients may include a complete blood count, abdominal ultrasound or CT, EKG, and creatine kinase (CPK) to evaluate acute abdominal and chest pain syndromes

General supportive management (airway protection, breathing and circulation per advanced cardiac life support protocols) must

be instituted promptly Most black widow spider envenomations may be managed with opioid analgesics and sedative - hypnotics

A specifi c antivenin for black widow bites is available Although

it results in resolution of most symptoms 30 minutes after admin-istration and has been shown to decrease the need for hospitaliza-tion signifi cantly, it should be cautiously restricted for severe envenomations, due to hypersensitivity, anaphylaxis, serum sick-ness reactions, and even risk of death [1,185,187] Antivenom should be considered when envenomation seriously threatens pregnancy or precipitates potentially limb - or life - threatening effects (e.g severe hypertension, unstable angina) As is the case with snake antivenoms, it should be given only in the hospital setting for the possibility of anaphylactic reactions [172] The antivenin is derived from horse serum must be diluted (in 2.5 ml

of normal saline) and administered slowly (200 ml over an hour) after skin testing and antihistamines to reduce acute adverse reac-tions to the antivenom [182] One to two vials are generally

suf-fi cient to counteract the nanomolar concentrations of circulating black widow spider venom; however additional dosing may be necessary in patients who do not demonstrate adequate recovery [188] Symptoms have been shown to improve within 1 hour of

Spider b ites

In the USA, spider bites during pregnancy are reported four times

more frequently than snake bites (see Tables 39.25 and 39.27 ) In

the USA only two types of poisonous spider bites are of concern:

the black widow and the brown recluse These spiders bite only

when trapped or crushed against the skin [181]

The adult female black widow spider ( Latrodectus mactans ) has

a highly neurotoxic venom ( α - latrotoxin), which destabilizes the

cell membranes and degranulates nerve terminals resulting in

massive norepinephrine and acetylcholine release into synapses,

causing excessive stimulation and fatigue of the motor endplate

and muscle [172,182]

Membrane receptors that bind α - latroxin have been identifi ed:

neurexin and latrophilin/CIRL (calcium - independent receptor

for α - latrotoxin) Although the nervous system is the primary

target of low doses of α - latrotoxin, cells of other tissues (placenta,

kidney, spleen, ovary, heart, and lung) are also susceptible to the

toxic effects of α - latrotoxin because of the presence of CIRL - 2, a

low - affi nity receptor of the toxin [183] Although it is known that

this venom does not affect the CNS due to its inability to cross

the blood – brain barrier, it is not known whether it crosses the

placenta or has direct fetal effects [182]

The diagnosis of a black widow spider bite is mainly clinical

The venom does not contain infl ammagens so the site of the

envenomation is usually unremarkable except for a small circle

of erythema and induration [172,182] Within about one hour of

the incident (minutes to hours), patients develop an autonomic

and neuromuscular syndrome characterized by hypertension,

tachycardia, and diaphoresis, abdominal pain and tenderness,

and back, chest, or lower extremity pain (painful muscle spasms

and cramping), and weakness [181,184,185,186] Muscle

Table 39.27 Insect and arthropod envenomation by category of exposure and maternal effects, US: 1999

Miscellaneous insects 97 6 (6.1%) 31 (31.9%) 3 (3.1%) 56 (57.7%)

Minor effects are signs or symptoms developing from the exposure but minimally bothersome and generally resolving without residual disability A moderate effect is one that is more pronounced or prolonged than minor effects, usually requiring some form of treatment Major effects (exposure resulting in life - threatening signs or

symptoms or results in signifi cant disability or disfi gurement) were not reported in this series

(From Gei AF, Van Hook JW, Olson GL, Saade GR, Hankins GDV Arthropod envenomations during pregnancy Report from a national database — 1999 (Abstract no 0662) Annual Meeting of the Society for Maternal – Fetal Medicine, Reno, Nevada, 2001.)

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Systemic involvement, although uncommon, occurs within

24 – 72 hours of the bite more frequently in children than in adults These systemic envenomations may be life threatening, and present with fever, constitutional symptoms (low - grade fevers, diarrhea, vomiting), petechial eruptions, thrombocytope-nia, and hemolysis with hemoglobinuric renal failure, seizures or coma, and usually associated with minimal skin

after a bite by L laeta , prevalent in Peru, Chile, and part of Brazil

[190] Treatment of envenomations is hindered by the delayed pre-sentation of the victims to a medical facility and overdiagnosis Unfortunately by the time a necrotic ulcer develops it may be too late for interventions The treatment of local envenomations is mainly conservative (immobilization and elevation, application

of ice, local wound care, tetanus prophylaxis, analgesics, and close follow - up) The application of ice in theory decreases the damage and infl ammation and local spread of the venom through vaso-constriction (application of heat results in more severe damage) Severe brown recluse spider bites produce dermonecrosis within

72 – 96 hours Early surgical management in general has been found to be ineffective and sometimes harmful as an initial man-agement technique [172,190] Skin grafting may be necessary after 4 – 6 weeks of standard therapy or until the lesion borders are well defi ned

Given its leukocyte inhibiting properties, dapsone has fre-quently been recommended for the treatment of local lesions However, because of the potential for adverse effects associated with dapsone use, especially in the setting of glucose - 6 - phosphate dehydrogenase defi ciency, hypersensitivity, cross - reactivity with sulfa allergies and methemoglobinemia, appropriate caution should be exercised if using this medication To date, no well controlled studies have shown dapsone to affect clinical outcome

in human brown recluse envenomations; therefore, it is not rou-tinely recommended [172,190]

antivenom administration and for as long as 48 hours after

envenomation [182,188]

Analgesics (morphine) and benzodiazepines (midazolam) are

effective adjuvant treatment for the neuromuscular symptoms

black widow spider envenomation [1] Antibiotics are not

indi-cated unless specifi c signs of cellulitis are noted A booster of the

tetanus toxoid should be given following a black widow spider

bite

In the particular case of pregnancy, black widow

envenom-ations can mimic acute intra - abdominal processes [186,189] and

preeclampsia (abdominal pain, headache, hypertension, and

pro-teinuria) [182] Hospitalization and treatment with specifi c

anti-venom is recommended given that maternal mortality has been

postulated to be as high as 5% [174,186]

In 1999, 22 bites by black widow spiders were reported to

Poison Control Centers in the USA (Table 39.27 ) Half of the

women reported only minor effects and another fi ve women

(18.7%) reported effects requiring some form of treatment The

outcome was not known in four cases [170]

Loxosceles spiders have a worldwide distribution in temperate

and tropical regions There are approximately 50 recognized

Loxosceles species in North America [190] Loxosceles recluse is

perhaps the best known member of the family and along with

Loxosceles deserta are endemic and responsible for the majority of

documented bites Characteristic violin - shaped markings on

their backs have led brown recluses to also be known as “ fi

ddle-back spiders ” though these markings may not be visible without

magnifi cation and may vary according to spider variable color

In South America, the more potent venom of the species Loxosceles

laeta is responsible for systemic loxoscelism and several deaths

each year The usual habitat of the brown recluse is in dark closet

corners and the sides of cardboard boxes and can infest in large

numbers Although not aggressive, the spider will bite when

trapped [190]

The venom of these spiders has variable toxicity depending on

the species It contains at least nine enzymes, consisting of various

lysins (facilitating venom spread), hyaluridonidase, and

sphingo-myelinase D, which causes cell membrane injury and lysis,

thrombosis, local ischaemia, and chemotaxis [172,190] Loxosceles

venom is also capable of inducing systemic intravascular clotting,

which can result in hemolysis and renal failure [190]

Although most bites are asymptomatic, envenomation can

begin with severe burning pain (characteristic of these

envenom-ations) and itching that progresses to vesiculation (single clear or

hemorrhagic vesicle) with violaceous necrosis and surrounding

erythema, and ultimately ulcer formation and necrosis

(der-monecrotic arachnidism) (see Figure 39.5 ) The differential

diag-nosis includes arterial injection injury, herpes simplex,

Stevens – Johnson syndrome, vasculitis, purpura fulminans,

nec-rotizing fasciitis, and toxic epidermal necrolysis among others

[190]

Loxoscelism is the term used to describe the systemic clinical

syndrome caused by envenomation from the brown spiders

Figure 39.5 Effects of Loxosceles reclusa bite (Photograph courtesy of Dr

Ramon L Sanchez; Galveston, Texas.)

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clinical effects of envenomations are neuromuscular and neuro-autonomic [175] A grade III envenomation is characterized by either cranial/autonomic or somatic skeletal neuromuscular dys-function, including blurred vision, nystagmus, hypersalivation, tongue fasciculations, dysphagia, slurred speech, respiratory dis-tress; restlessness and severe involuntary shaking or jerking of extremities that may be mistaken for a seizure A grade IV com-bines cranial/autonomic and somatic nerve dysfunction [175] Most commonly, an infl ammatory local reaction occurs with the envenomation, which is treated with wound debridement and

Antivenom is recommended for grade III and IV envenomations [195] In Israel and India control of the overstimulated autono-mous system has been successfully achieved with the use of β blockers (prazosin), calcium - channel blockers (nifedipine), and angiotensin - converting enzyme (ACE) inhibitors (captopril) [169]

In 1999, 165 scorpion envenomations were reported by preg-nant women in the USA In those patients with known outcome, minor symptoms were predominant No life - threatening symp-toms or signs were reported (see Table 39.27 ) [170]

Summary

1 Poisoning during pregnancy represent a third of a percent of

all toxic exposures reported in the USA

2 The number of reported toxic exposures has increased by about 25% over the past 6 years both in the pregnant and non pregnant population

3 Although slightly more frequent during the second trimester,

toxic exposures during pregnancy are reported with similar fre-quency in all trimesters

4 The emergency treatment and stabilization of the mother should take priority over the monitoring and treatment of the fetus

5 A prompt consultation with the obstetric service is

recom-mended in the emergent management of the compromised poi-soned pregnant patient The goals of this consult are: (a) the assessment of fetal viability and (b) the decision/skill to proceed with an emergent or perimortem cesarean section, if the resusci-tative efforts are not successful and/or the patient ’ s condition worsens

6 The mechanism of exposure needs to be sought and

estab-lished, since intentional toxic exposure usually indicates severe social, emotional and/or psychiatric pathology When identifi ed, the need for additional and aggressive intervention (hospital admission, social and psychiatry consults, etc.) may prevent a potentially fatal recurrence

7 Insect and arthropod exposures are not uncommon during

pregnancy The majority of these envenomations resulted in minor or no effects Moderate effects are more likely when the cause of the exposure is a spider bite than with other arthropod exposures, including scorpion and bee stings

Other treatments, such as colchicine, steroids, antivenom,

nitroglycerin patches, hyperbaric oxygen, and surgical excision,

have been reported but insuffi cient data exist to support their

clinical use [190] Intradermal anti - loxosceles Fab fragments have

been shown to attenuate dermonecrotic arachnidism in a rabbit

model when given up to 4 hours after venom inoculation [192]

This treatment has not yet been applied clinically [190]

Antivenom is not commercially available for Loxosceles reclusa

There are four sources of commercial Loxosceles antivenoms,

none of which is available in the USA [190] In countries where

antivenom is available the usual indication is systemic

loxosce-lism and it is likely that its use is capable of decrease the size of

the lesion

Systemic envenomation requires supportive care and

treat-ment of arising complications, corticosteroids to stabilize red

blood cell membranes, and support of renal function

Patients with an isolated dermal lesion who will be discharged

home should be instructed to watch carefully for a change in the

color of the urine because the can develop a delayed systemic

reaction [190]

Anderson [193] reported fi ve cases of envenomation by

Loxosceles reclusa in pregnant patients He concluded that no

special risks or complications resulted from being bitten by the

brown recluse during pregnancy when managed only with low

dose prednisone No instances of hemolysis, disorders of

coagula-tion, or renal damage were reported in this case series In 1999,

23 bites by brown recluse spiders were reported to Poison Control

Centers nationwide Of those bites, the outcome is unknown in

the majority (13) and moderate effects (more pronounced or

prolonged than minimal; usually requiring some form of

treat-ment) were reported in three cases [170]

Scorpions

Over 650 species of scorpions are known to cause envenomation

(mostly to children under 10 years); they are endemic mostly in

arid and tropical areas In developing countries scorpion stings

are associated with mortality ratios of up to 0.2% [194] Different

venoms and clinical presentations are seen across the different

species Systemic envenoming is caused by members of the genera

Centruroides (found in Southwest USA and Mexico), Tityus

(Brazil and Trinidad), Androctonus , Buthus , Leiurus , and Nebo

(North Africa, Near and Middle East); Hemiscorpius (Iran and

Iraq); Parabuthus (South Africa), and Mesobuthus (Indian

sub-continent) [169] The scorpion of primary concern in the USA is

Centruroides exilicauda (formerly sculpturatus ) which has a sting

that is potentially fatal [195]

In general scorpion stings produce an immediate sharp,

burning pain that may be followed by numbness extending

beyond the sting site Regional lymph node swelling may also

occur Less frequently ecchymosis and lymphangitis develop

[195] Scorpion envenomations and snake bites can be graded

similarly A grade I envenomation is characterized by local pain

whereas remote pain and/or paresthesias remote from the sting

site characterize a grade II envenomation The most important

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17 Bayer MJ , Rumack BH Poisoning and Overdose Aspen Systems,

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18 McElhatton PR , Roberts JC , Sullivan FM The consequences of iron

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19 Richards S , Brooks SHE Ferrous sulphate poisoning in pregnancy

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20 Strom RL , Schiller P , Seeds AE et al Fatal iron poisoning in a

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23 American Heart Association Cardiac arrest associated with

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36 Tenenbein M Position statement: whole bowel irrigation American Academy of Clinical Toxicology; European Association of Poison

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37 Olson K Poisoning and Drug Overdose , 2nd edn Norwalk, CT :

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38 Weisman RS , Howland MA , Flomenbaum NE The toxicology labo-ratory In: Goldfrank LR , Flomenbaum NE , Lewin NA et al

8 Regardless of their severity, all toxic exposures need to

be reported to the respective Poison Control Center

(+1 - 800 - 222 - 1222)

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