Ryan Buban is a 6-year-old boy residing in Rocklin, California with his mother, Taylor Fitzgerald. He is among those who became severely ill after consuming E. coli contaminated romaine lettuce. On April 10, 2018, Ryan consumed a salad containing E. coli contaminated romaine lettuce from the Papa Murphy’s located at 44819 Granite Drive Ste A, Rocklin, California.

Ryan Buban

Symptom Onset

On April 12, 2018, Ryan began to experience gastrointestinal and other symptoms including stomach cramps, fever, muscle aches, fatigue, gas, and headache. By April 14, Ryan was suffering from bloody diarrhea.

Ryan’s mother, Taylor, recalls coming home to find Ryan with a frightening array of symptoms:

… I arrived home from work as a flight attendant at approximately 11 pm. Ryan was staying with my parents and upon my arrival my Dad told me that Ryan had been under the weather and his condition had been worsening. He told me Ryan had had stomach pain and diarrhea that had started turning bloody. I instantly rushed Ryan to the emergency room where he continued to have pain and bloody diarrhea.

Sutter Roseville Medical Center

It was almost 11:30 PM on April 14, 2018 when Taylor arrived with Ryan at Sutter Roseville Medical Center, where Ashley Pilgrim, MD evaluated him in the emergency department. In triage, Taylor described that her little boy had been having abdominal pain for four days, and on day three began to have severe diarrhea. The pain and diarrhea were gradually worsening and his stools were now bloody. Taylor stated that Ryan also had a fever that morning. He also had a rash on his chest. Melissa McClanahan, RN wasted no time getting Ryan into an exam room, where Dr. Pilgrim saw him shortly after midnight on April 15^th.

Dr. Pilgrim observed that Ryan looked miserable and uncomfortable. She asked about any recent exposures to illness or suspect foods, and Taylor could not think of any except for some sushi they had four days before he started having symptoms. On exam, Ryan did not have a fever, but he was diffusely tender in the left lower quadrant of his abdomen, without any rebound or guarding. Rectal inspection was unrevealing of any fissures or external hemorrhoids. Dr. Pilgrim ordered lab work, which soon returned results showing a normal platelet count, hemoglobin, and urinalysis; a test for fecal leukocytes was negative, and stool studies for toxigenic C. difficile and culture were pending.

While Ryan was under observation in the ER, Dr. Pilgrim administered intravenous fluids and gave him IV morphine and oral Tylenol for pain. Although Ryan felt “remarkably improved” after the above interventions, he continued to pass “bright red blood per rectum,” and Dr. Pilgrim had to consider that there might be some very serious causes for his gastrointestinal bleeding, including but not limited to volvulus, obstruction, Meckel’s malrotation, torsion, intussusception, mesenteric adenitis, hemolytic uremic syndrome, or some other more emergent diagnosis. She therefore consulted with the pediatric intensivist at Sutter Medical Center in Sacramento, who concurred and accepted Ryan for transfer to their hospital.

Taylor recalls the ER visit:

The frequency of this diarrhea was so severe I needed to put him into a diaper in order to check in at the front desk. While we waited to be seen Ryan began to get very pale and lethargic and began to become very weak so I carried him to the front desk and told the Nurse I was starting to become very worried about his decreasing health to which they alerted me that they too had noticed how severely ill he is and how his health was diminishing so he was a priority stat to be seen. When we got into the room in the ER they immediately started Ryan on morphine due to the high level of pain he was in and an IV drip due to his dehydration, he was also showing signs of anemia from the blood lost in his stool. The doctor told us Ryan was too sick to be treated there and needed to be transported by ambulance to Sutter Sacramento pediatric department where they would be better equipped to handle him. We took an ambulance ride and Ryan’s pain grew more and more severe along the way.

Sutter Medical Center – Sacramento – Day 0

At 4:08 AM on April 15, 2018, American Medical Response ambulance crew were on site to transfer Ryan from Roseville to Sacramento, about half an hour ride south. Ryan arrived at Sutter Medical Center – Sacramento just after 5 AM, where he bypassed the emergency department for a direct admit to the general pediatric floor by Samuel Abebe, MD.

At 6:01 AM, Dr. Abebe examined Ryan. He discussed the onset and course of Ryan’s diarrheal illness with his mom, finding it notable that the boy had been in his usual state of good health until four days earlier. He reviewed Ryan’s brief ER records from Roseville and agreed with the findings of Dr. Pilgrim. On exam, however, Ryan exhibited more pain and had guarding[1]during his current abdominal exam, and he was slightly tachycardic with a pulse of 101. Dr. Abebe continued Ryan’s IV fluids and went over his intake lab results: WBC 10.7, hemoglobin 12.2, hematocrit 36.1, platelets 293, BUN 11, creatinine 0.24, and urinalysis clear except for ketonuria 2+.[2]His stool studies were pending.

Possible intussusception on ultrasound

Ryan’s condition was stable but unimproved throughout the day, so imaging was ordered. At 6 PM, radiologist Michael Doratan, MD performed an abdominal ultrasound, during which he identified a “thick-walled colon” as well as moderate free fluid in Ryan’s abdomen. He identified a worrisome area in the right lower quadrant that concerned him for possible intussusception[3]and advised closer inspection with a contrast-enhanced CT. Dr. Doratan discussed his findings with the pediatric care team, who requested the CT scan and a surgical consultation.

CT evidence of severe colitis

At 9:48 PM, radiologist Jason B. Wiesner, MD performed an oral- and IV-contrast-enhanced CT scan of Ryan’s abdomen and pelvis. He confirmed multifocal colon wall thickening, particularly in the cecum, ascending colon, and descending and rectosigmoid colon. He observed sparing of the transverse colon consistent with multifocal colitis. Dr. Wiesner thought the CT imaging was consistent with either an infectious or inflammatory etiology. He saw no evidence of intussusception, obstruction, or perforation, and Ryan’s appendix looked unremarkable to him. He thought the ascites[4]was mild and likely reactive.

Lisa Abramson, MD came in for a pediatric surgical consultation just before 10 PM and talked to Taylor about Ryan’s illness. Taylor described the onset of her son’s illness, which began with abdominal pain and loose stools, followed by constant diarrhea with bright red blood in the toilet bowl. She stated that Ryan continued to experience intermittent worsening of the crampy abdominal pain, followed by a small amount of relief. Taylor told Dr. Abramson that she initially thought that Ryan’s illness could be due to a stomach bug, but when his pain became constant and he continued to have bloody diarrhea, she brought him in for evaluation. She stated that Ryan also experienced subjective fevers and chills, but he had not been nauseated or vomited. Dr. Abramson found it notable that one else in the family was experiencing symptoms, including Taylor, who ate the same thing as Ryan at the sushi restaurant.

On exam, Dr. Abramson found Ryan “awake, alert, tired, scared.” She observed no peritoneal signs or other worrisome physical findings. She reassured him and his mom that she saw no reason for surgery, especially with a normal appendix; however, he did have colitis, which was causing his bloody diarrhea and abdominal pain. She explained that the stool studies from Roseville would help his doctors to identify his diagnosis, but those results were not in yet. Based on the nonsurgical findings, Dr. Abramson signed off Ryan’s case and deferred further management to his pediatric team.

Taylor recalls a terrible first night in the Sacramento:

When we reached the hospital, Ryan was screaming out in pain. He would beg for us to help him, the worst feeling as a mother is having your child beg for help and you can’t do anything.

Ryan was on the highest dose of oxycodone, morphine and IV Tylenol, yet still was screaming in agony. During this time doctors were rushing to figure out what was wrong with Ryan. We went through a series of tests, an ultrasound and a cat scan. Eventually Ryan’s pain was so severe he looked at me and told me he thought that god was trying to kill him. I tried to assure him everything was going to be okay but he was in so much pain and I was so helpless. It was the most emotionally draining thing to have him constantly look at me in the eyes and say “mommy help me! Please help me! Why isn’t anyone doing anything to help me?”

Sutter Sacramento – Hospital Day 1

At 5:17 AM on April 16, 2018, Laurel Davies, RN observed that Ryan continued to have frequent, blood streaked diarrhea. He appeared to have increased pain during his bowel movements and was medicated during the night two times with oxycodone, in addition to Tylenol and two doses of IV morphine. When this still did not control Ryan’s pain, she paged Dr. Abebe, who approved an additional dose of morphine. Ryan’s mom and his grandma were present at his bedside. To his humiliation, Ryan had to remain in a diaper because of his diarrhea, as well as being hooked up to monitors and IV lines—not to mention the pain medications that made it unsafe for him to be ambulatory.

Pediatric gastroenterologist Johan Milian, MD came in for a consultation around noon, reviewing the imaging from the night before and examining Ryan. He reviewed his morning lab results, which showed a WBC 9.7, hemoglobin 10.5, hematocrit 31.2, platelets 278K, BUN 2, and creatinine 0.19. His C-reactive protein[5]was marginally elevated at 10.0. His stool was reported as negative for fecal leukocytes as well as toxigenic C. difficile, but the culture and O&P tests were still pending. Dr. Milian agreed with a diagnosis of acute colitis, which he thought was most likely infectious. He explained to Ryan’s mom and grandma that antibiotics were not advisable at this point, at least until the stool culture results were available. If the stool tests were negative, he advised a colonoscopy and upper endoscopy to evaluate for possible inflammatory bowel disease. He wanted to follow Ryan’s labs at least twice a week, in case he developed hemolytic-uremic syndrome, worsening anemia, or other problems.

Lehman Black III, MD came in for the pediatric hospitalist service at 1:21 PM and continued Ryan’s orders for pain medication, increasing his morphine dose but discontinuing the oral oxycodone so they would be using only a single narcotic. He concurred with the plan to avoid antibiotics.

Sutter Sacramento – Hospital Day 2 – confirmation of Shiga toxin 2 with E. coli O157:H7

On April 17, 2018 at 6:39 AM, Karla Wellsfry, RN came on shift and was happy to hear that Ryan had slept well most of the night. He had required IV narcotics every three hours to control his pain, in addition to an antispasmodic medication for his severe abdominal cramping. The nurse noted that Ryan’s stool was lessening but had a foul odor and looked “mucoid/green/loose and some blood streaks.” He was unable to tolerate any fluids by mouth; however, he was able to take two bites of his breakfast before refusing anything further.

At 12:50 PM, the Sutter Roseville hospital laboratory sent a written critical alert by fax to Sutter Sacramento, reporting that Ryan’s stool was positive for growth of E. coli O157:H7 and was positive for Shiga toxin 2, and negative for type 1. The Roseville lab reported Ryan’s E. coli infection to the health authorities and sent the isolate to the State of California Department of Health laboratories for confirmatory testing.[6]The remainder of his stool tests were negative.

Pediatric hospitalist Dr. Black came in to see Ryan shortly after learning that he had tested positive for Shiga toxin associated E. coli O157 (STEC). He took a look at Ryan’s morning labs and noted no current evidence for HUS.

Taylor recalls the terror she felt at when hearing of Ryan’s STEC diagnosis:

At one point I changed [Ryan’s] diaper and almost passed out because there was so much blood. I didn’t want him to see how worried I was so I quickly wrapped it up and put it aside but deep down inside I was scared because I knew something was very wrong. We eventually got the diagnoses that Ryan had shiga toxin caused by E. coli. This shiga toxin was creating a poison in his colon which led to extreme colitis. This was the reason for the pain. We continued to help as best we could and medicate him to try to make him more comfortable. The doctor let us know that there was a small chance that Ryan could develop HUS syndrome, and that there is no way to tell which child it will affect, so we would monitor for that as well.

Sutter Sacramento – Hospital Day 3

On April 18, 2018, Dr. Black returned to see Ryan and noted his condition was stable and improving, although he continued to require around-the-clock morphine dosing to control his severe abdominal pain. Dr. Black again saw no evidence of HUS on the morning labs. The nursing staff observed that Ryan’s urinary output was “adequate,” and his stools now contained only red mucous and no frank blood.

Later in the day, Ryan was visited by Ryan Cooper of Child Life Services to help him cope with being in the hospital. Mr. Cooper described Ryan as “anxious and upset (crying); pt slow to recover.” His mom explained that this was his first day without morphine, and he had been very “cranky” and difficult to console. Mr. Cooper explained that Ryan’s fearful and guarded behavior was a developmentally appropriate response to hospitalization. Ryan became more relaxed during the visit and talked about how he enjoyed Legos and video games. However, he became immediately anxious and resistant when his mom asked him to take a chewable vitamin. Mr. Cooper thought that Ryan might benefit from “medical play” to promote a greater understanding of hospitalization and to allow for expression of his emotions.

Sutter Sacramento – Hospital Day 4 – STEC Hemolytic Uremic Syndrome (HUS)

On April 19, 2018 at 4:21 AM, Amanda Whitling, RN documented a low-grade fever of 100.6ºF and gave Ryan a dose of Tylenol. Later that morning, the laboratory reported critical values related to his blood count, noting an abrupt drop in his hemoglobin and hematocrit to 9 and 28.8%, and his platelets had fallen to 81K. The nursing staff alerted Dr. Black, who came in to see Ryan after conferring with nephrology.

Ryan’s doctors concluded that he had now developed hemolytic uremic syndrome and ordered continued serial laboratory measurements of his renal function, anemia, and platelet counts. Dr. Black discussed Ryan’s HUS diagnosis with his mom and reassured her that her son’s renal function was currently normal and he seemed to be urinating well, so he expected his prognosis to be “very good.” He explained that they would be monitoring his lab values twice daily from that point and a pediatric nephrologist was now involved in Ryan’s case. The Washington State Health Department was informed of Ryan’s diagnosis of STEC HUS.

If Taylor thought she was terrified before, the sense of danger only intensified with this new diagnosis, as she recalls:

On April 19^thRyan’s hemoglobin and platelets dropped into the abnormal range which meant he had developed HUS. I was devastated and scared. The doctor explained to us that there was nothing we could do as HUS was untreatable except for preventive care and monitoring him. I researched HUS all night, I saw that there was a 3-5 percent mortality rate and I had to go into the bathroom and throw up. I couldn’t understand how my perfectly healthy boy had turned so ill in a matter of days.

Sutter Sacramento – Hospital Day 5 – nephrology consultation

On April 20, 2018, the lab reported further worsening of Ryan’s thrombocytopenia (platelets 50K) and anemia (hemoglobin 7.4, hematocrit 21.2), although his renal function was stable (BUN 23, creatinine 0.83).

Pediatric nephrologist Arundhati Kale, MD came in for a consultation during the afternoon. She looked over Ryan’s lab results since he was admitted, observing that his CBC and metabolic panel were normal until the 19^th, at which time his serum creatinine increased from to 0.26 to 0.78, and his BUN from 2 to 23. In addition, his CBC showed progressive hemolytic anemia and thrombocytopenia, consistent with a diagnosis of STEC HUS. She commented in her chart note:

[Ryan] has been well hydrated with IVF and is currently non-oliguric. Last Hgb 7.4, down from admission value of 12.2; plt down to 50K down from 293.

Dr. Kale found it notable that Ryan exhibited marked behavioral changes, becoming irritable and complaining continually of abdominal pain. However, his diarrhea was improving with no more blood in his stools, and his urine output had been measured at about two liters a day. Dr. Kale commented: “The source of his infection is unclear; mom reports his eating raw salad from Papa Murphy’s prior to the onset of diarrhea.” Dr. Kale ordered renal dosing of all of Ryan’s medications and advised minimizing his fluid intake if he became oliguric. She advised a regular diet but leaning towards low-potassium foods. She recommended a transfusion of packed red blood cells (pRBCs) if Ryan’s hemoglobin dropped below 6 g/dL. Dr. Kale saw no clinical indications for hemodialysis at this point, but she discussed the possibility in detail with his mother. She explained the diagnosis of HUS and what to expect if the disease progressed, including the possible complications of anuric acute kidney injury (AKI) that could lead to dialysis.

That evening, it took the lab technician three attempts to collect Ryan’s blood. His results were back at 10 PM, showing worsening of his thrombocytopenia and anemia, but stable renal function (hemoglobin 6.6, hematocrit 18.9, platelets 31K, BUN 23, creatinine 0.76). The nursing staff reported these values to Dr. Duong-Tran, who ordered that Ryan be placed on supplemental oxygen 2 liters/min by mask because of his low hemoglobin and hematocrit.

Sutter Sacramento – Hospital Day 6 – hemolytic anemia, blood transfusion

On April 21, 2018, Shannon Reid, RN documented that Ryan’s urinary output was currently 3.6 ml/kg/hr[7]and was straw to tea-colored. He was passing small, blood-streaked stools. Around noon, the morning lab results were reported, showing that Ryan’s hemoglobin had fallen to 5.4, his hematocrit was 15.8, and his platelets were down to 22K. His BUN and creatinine were 22 and 0.68. The nurse reported these values to Maha Haddad, MD of pediatric nephrology, who ordered a blood transfusion of pRBCs. Dr. Haddad was concerned that Ryan had become tachycardic with the development of severe hemolytic anemia, but she did not think he needed to be fluid-restricted at this point, as his urinary output was still “good.”

Unfortunately, Ryan’s peripheral line failed that evening, and his IV fluids infiltrated the subcutaneous tissues of his left hand, causing it to become edematous and painful. The nurse had the blood transfusion line spiked and ready to go when this occurred, and she gave a STAT page to the infusion therapy staff to come and restart Ryan’s line. She also called Child Life to come assist Ryan with this traumatic event. Ryan got through this and received his first blood transfusion.

Taylor recalls feeling helpless that she could only stand by and watch her son suffer, who looked so small and ill:

The next weeks were an absolute blur. They would test Ryan’s blood sometimes every hour. He had bruises up and down his arms from all of the needle pokes. Sometimes his IV would get clogged and they would have to rush in and start a new one. He wouldn’t eat and couldn’t get out of bed. His blood levels continued to drop, at one point the nurses rushed in the middle of the night explaining that Ryan required an emergency blood transfusion. He was barely conscious and pale, his lips were blue, and I have never been so scared in my life.

Sutter Sacramento – Hospital Day 7 – volume overload and hypertension

At 1:27 AM on April 22, 2018, Ryan’s mom alerted the nursing staff of a new change in her son’s behavior:

Called into room by mom, patient awake, screaming, hitting and angry. Mom states, ‘I have not seen this level of aggression for him, this is not who he is.’ Patient denies pain, answers questions appropriately, but is adamant that mom is lying and is angry that she ‘annoyed him.’ Aside from current behavior neuro exam is appropriate and unchanged. Will monitor closely for changes.”

Ryan calmed down but had other behavioral episodes that morning, and he required a dose of morphine for severe left leg pain. The nursing staff noted that his urine was dark amber in color but “adequate” in quantity. Ryan’s mom noticed that his feet looked yellow, and the nurses observed they felt cool to the touch.

Dr. Haddad came in for pediatric nephrology around 10 AM, observing that, despite his blood transfusion, Ryan continued to exhibit active hemolysis and both his platelet count and hemoglobin continued to drop (platelets 9K, hemoglobin 5.50. She was concerned about his left leg pain, as well as petechiae that showed up on his tongue.

The doctor also observed that Ryan’s blood pressure was increasing and he was exhibiting other signs of volume overload, although his urinary output remained “good” and his renal labs were stable (BUN 24, creatinine 0.6). Dr. Haddad changed Ryan to a renal diet and started him on fluid restriction for volume overload. She ordered antihypertensive medication (amlodipine) to be dosed once daily, with a plan to increase it to twice daily if his blood pressures remained elevated. She added liver function and pancreatic function to his lab tests, which later yielded a number of abnormal results (AST 78, total bilirubin 1.6, lipase 887). Given Ryan’s active hemolysis and falling hemoglobin, he received another transfusion of pRBCs that afternoon.

To Taylor, there seemed to be no end to the suffering Ryan had to endure:

Ryan required 3 more transfusions. It felt like we always took two steps forward and one step back. Anytime his levels would raise up, they would drop back down. The doctor had warned us about kidney failure, and the signs to look out for. One afternoon, Ryan’s urine came out dark brown. My heart sank because I knew this meant he had started the stages of kidney failure. Every day was such a challenge because you had to sit and wait to see how bad things were going to get. HUS syndrome causes extreme aggression and temperament, at some points Ryan was punching, kicking, screaming at me and even pulling my hair. It was so out of character because he is such a loving outgoing child. He would have extreme fits of rage, sometimes we would have to pin him down so he couldn’t injure himself or pull out his IV. I remember one specific time where he needed to have oxygen on and he kept ripping it out so we had to forcefully hold his arms at his side while he thrashed around screaming at us to get off of him. It was horrible. It usually took about 3 nurses to take his blood because he would require being held down.

Sutter Sacramento – Hospital Day 8-9 – two more blood transfusions

On April 23, 2018, Ryan’s morning labs reflected little improvement of his hemolytic anemia (hemoglobin 6.0, hematocrit 16.7) with only a slight improvement in his platelets to 16K. His BUN and creatinine remained stable at 21 and 0.67. Candace Eyman, MD came in for the pediatric hospitalist service, noting that Ryan continued to pass bloody stools but no longer had diarrhea. She thought Ryan looked listless, but his muscle tone seemed okay. His hypertension appeared to be stable on the antihypertensive medication.

Ryan received his third blood transfusion that afternoon, and his labs that evening reflected improvement (hemoglobin 8.0, hematocrit 22.3). Dr. Eyman ordered another transfusion if his hemoglobin fell below 6.5, as opposed to the previous alarm value of 6.0 to avoid any delay in his receiving treatment.

Dr. Kale came in for nephrology on April 24 and was happy with Ryan’s urinary output, although she commented on the gradual increase in his serum creatinine levels compared to those on admission. Dr. Eyman came in to see Ryan in the afternoon, at which time he reported a worsening cough. She ordered a chest x-ray, which revealed he had a small right pleural effusion.

Ryan required a fourth blood transfusion the evening of the 24^th, when his labs demonstrated a drop in his hemoglobin to 5.8. After the transfusion, his hemoglobin improved to 7.3, although his white count was elevated at 14.7.

Sutter Sacramento – Hospital Day 10-11 – HUS improving

On April 25, 2018, Dr. Black came in for the pediatric hospitalist service on and observed that Ryan now had a normal white count of 9.0. He exhibited stable, if still severe, hemolytic anemia (hemoglobin 7.5, hematocrit 21.8), and a stable BUN and creatinine of 23 and 0.59. He continued to urinate in “adequate” volumes. Dr. Black told Ryan’s mom that his HUS appeared to be resolving, although he remained critically anemic. They discussed the use of Epogen[8]if his blood counts did not start improving.

Dr. Black came in on the 26^thand was happy to see that Ryan’s anemia was stable since the last blood draw, although his hemoglobin had fallen slightly (7.5 to 7.3). His platelets increased from 73K to 108K overnight. Dr. Black thought they could continue with daily blood draws instead of twice daily as long as that trend continued. Ryan appeared to be getting more active and was feeling better as well. Dr. Black conferred with nephrology about giving Ryan a single dose of Epogen versus just watching his blood hemoglobin and reticulocyte counts. The dietician came in and encouraged more food choices, as long as his snacks were not high in sodium, as Ryan was no longer on a full renal diet. His blood pressures were doing well and he was taken off the antihypertensive medication.

Sutter Sacramento – Hospital Day 12 – continued recovery

Stephanie Nguyen, MD visited Ryan for the nephrology service on April 27, 2018, noting that he had received a total of four blood transfusions so far. His labs that morning showed continued severe hemolytic anemia (hemoglobin 6.8, hematocrit 20.3). His blood pressure remained in normal range off amlodipine. Dr. Nguyen was happy to see good platelet recovery (now 182K); however, she was concerned that Ryan continued to exhibit ongoing hemolysis with a hemoglobin drifting downward since his last blood transfusion on the 24^th.

Dr. Nguyen disagreed with Dr. Black’s suggestion for one dose of Epogen, commenting: “Addition of erythropoietin stimulating agents like Epogen have not been shown to decrease the number of transfusions or reduce length of hospital stays in pediatric observational studies.” She agreed it would be safe to discharge Ryan once his hemoglobin remained stable and they could be sure of outpatient follow-up testing. Dr. Nguyen removed Ryan’s food restrictions and approved him for ad lib fluids, but she wanted to continue monitoring his intake and output. She discussed her assessment and plan with Dr. Black and the family.

Sutter Sacramento – Hospital Day 13-14 – discharge planning

On April 28, 2018, Ryan’s morning labs unfortunately exhibited another drop in his blood count to a hemoglobin of 6.7 and hematocrit 19.7. Dr. Abebe came in for the pediatric hospitalist service and did not think he needed another blood transfusion unless his hemoglobin fell below 6.5. He did not think that Ryan should be discharged home from the hospital with such a low blood count, however.

Dr. Abebe came in to see Ryan again on the 29^thand was happy to see that his hemoglobin had climbed to 7.2 overnight. He even considered letting Ryan go home that day, but his mom was uncomfortable with it because of how anemic her son still was. They agreed that they would like to see another day of improvement before considering discharge. Ryan’s renal function was stable and he was urinating well. He was feeling better and eating more, and his blood pressure was stable without any further antihypertensive medications.

Sutter Sacramento – Hospital Day 15 – going home

On April 30, 2018, Dr. Abebe came in to assess Ryan for discharge home. His hemoglobin had improved only slightly to 7.3, but he thought Ryan was stable enough to leave the hospital. He conferred with Dr. Nguyen, who concurred with a plan for close outpatient follow-up with her office and his pediatrician. Dr. Abebe discussed return precautions, including monitoring Ryan for respiratory distress, decreased oral intake, fever, persistent vomiting, or a return of his diarrhea. Ryan went home that afternoon.

Sutter Medical Foundation – Outpatient Pediatric Follow-up

On May 4, 2018, Ryan went to see pediatrician Claire Unis, MD in follow-up of his hospitalization for STEC HUS. Dr. Unis reviewed Ryan’s hospital records, opining that Ryan did exhibit oliguria at one point: “… urine was concentrated enough that it was dark and reddish in color.” She reviewed the progression of his illness to full-blown hemolytic syndrome, with thrombocytopenia as low as 9K. She also observed that Ryan had required several blood transfusions for severe hemolytic anemia, and he had required amlodipine to manage transient hypertension.

Dr. Unis expressed additional concerns in her chart note:

… According to chart notes and parent, [Ryan] also developed a cough while in the hospital approximately 10 days ago and was diagnosed with a small pleural effusion and fluid in his lungs. The cough has remained unchanged. Since his hospital discharge, they have noted that he gets easily fatigued when playing hard, gets short of breath and has fast [heartbeat], has to [lie] down to recover. Legs were shaky also. Mom has noted purplish color under the eyes. He was instructed to follow up with me for retesting regarding his anemia and has already had an appointment made for him with pediatric nephrology as well. He has not returned to school yet due to concern that he would not be able to rest enough. He has still been cranky and mom thinks due to fatigue. Not napping but will play quietly at these times. He is constantly going when he is well; he is not doing that right now.

On exam, Ryan’s pulse was rapid at 101, but he was afebrile and his blood pressure was in normal range. The remainder of his exam was unremarkable. Dr. Unis checked the results of blood tests she had run the day before this visit, which showed improving anemia (hemoglobin 8.4), elevated platelets (> 500K), an elevated reticulocyte count, and a normal white blood cell count. His urinalysis in the office that day was significant for proteinuria and trace blood. She asked Ryan’s mom to make sure he kept his appointment with the nephrologist in a couple of weeks and repeat his blood work and urinalysis at that time. Dr. Unis wrote Ryan a note to return to school and encouraged him to try to return to normal activity. Meanwhile, she sent his urine sample to the lab and advised him to return to see her in a month.

Taylor ended up bringing Ryan back to see Dr. Unis much sooner. On May 9, 2018, she discussed alarming behavior changes that had not gone away after Ryan was discharged from the hospital, including increased anger and aggression. Taylor stated that Ryan had been very irritable in the hospital with HUS, and she had become concerned that it was not getting better. “She was at first thinking it was just a reaction to being out of routine and not disciplined in hospital, but now worried it is related to his anemia or the HUS itself.” Taylor described a fit of rage a few days earlier that she had never seen Ryan exhibit before: “…  he had been mostly sweet and compliant before the hospitalization and never had prolonged bad behavior.” Ryan evidently now had daily episodes of being out of control. Dr. Unis described these episodes in her chart note:

… recently screaming he wanted to kill mom and wanted to die, ripped sheets off bed, kicked and hit the walls when put in time out. It lasted 3-4 hours before he could calm down. He was just as angry at mom’s roommate, said, ‘Get away! You are all evil!’ Once it was over he seemed totally normal and when mom asked why he was so angry, he said, ‘I don’t know.’ This is also out of character as usually he can articulate why he gets upset if he does. Not back to school yet, doing schoolwork at home. Mom has been checking in with another mom whose daughter had HUS at the same time and she has not had the same issues. No other acute social stressors, mom is on leave to care for him and both grandmothers are around and supportive.

Dr. Unis again identified nothing abnormal on exam, and she discussed Ryan’s behavioral changes with Taylor. She stated that, given that the complications associated with HUS could include stroke and seizure, and given that his behavior was dramatically different than baseline and not improving despite improving anemia and appropriate limit-setting by mom, it might be prudent for Ryan to have a brain MRI. In the meantime, she recommended finding a counselor for him. If necessary, she advised that they consider psychiatry for medication, if not getting any benefit from counseling, and/or a neurology referral depending on the MRI results.

On May 23, 2018, Ryan underwent a brain MRI at Sutter Radiology. James Steidler, MD performed the imaging both with and without contrast, and he deemed it a normal exam.

Ryan returned to see Dr. Unis on June 4, 2018. Ryan had not yet been back for any nephrology follow-up, and so Taylor requested a referral. On exam, Dr. Unis found Ryan still tachycardic with a heart rate of 114. He was afebrile but Dr. Unis considered his blood pressure to be slightly high at 113/68. She advised Taylor that Ryan could resume athletic activity, as he was otherwise healthy except for his recent HUS with hospitalization. She noted that his anemia, proteinuria, and behavior changes were all markedly improving. His hemoglobin and hematocrit were now 11.2 and 32.8, and his platelets were 361K. His urinalysis no longer showed any protein or blood. Taylor stated that Ryan was getting counseling, which seemed to be helping him greatly. Dr. Unis gave Ryan a nephrology referral, which Taylor indicated was the only reason he had not gone to see the specialist. Dr. Unis discussed Ryan’s slightly high blood pressure and told Taylor to keep him on a “no added salt” diet until nephrology cleared him otherwise.

UC Davis Health – Outpatient Nephrology

On September 5, 2018, Ryan and his mom presented to UC Davis for a new patient pediatric nephrology consultation and hospital follow-up with Kale Arundhati, MD. Although this was a “new patient” visit,Dr. Arundhati recalled consulting in-hospital for Ryan and was now seeing him again as an outpatient on referral by Dr. Unis.

Dr. Arundhati documented today’s findings in a letter to Dr. Unis in a letter of the same date. He reviewed Ryan’s hospital records, noting that the boy did get oliguric at one point, and his urine was concentrated enough that it was dark and reddish in color. In addition, he recalled that Ryan’s platelets had fallen as low as 9K, and he became so anemic he required three blood transfusions. Fortunately, he developed hypertension that proved to be only transient and did not require prolonged antihypertensive medications.

Dr. Arundhati was happy to learn that Ryan had no current signs or symptoms of hypotension (dizziness or lightheadedness at rest or upon arising). He had no urinary tract symptoms, including bedwetting or daytime incontinence, and did not have to get up at night to urinate. Ryan’s exam was unremarkable, including normal blood pressure. Dr. Arundhati deemed Ryan recovered from his E. coliHUS illness and, since dialysis was not needed, he indicated that his renal prognosis was very good. He cautioned Ryan’s mom that he still had a slightly higher risk of proteinuria/CKD in the future, for which he recommended an annual urinalysis and blood pressure measurement. At the end of the visit, Dr. Arundhati provided Ryan’s mom with lab slips for a CBC, metabolic panel, and urinalysis.

Aftermath

Ryan’s mother reflects on the impact of her son’s E. coli illness:

Every night I laid with Ryan and just prayed that one day I would be able to see him healthy again, I longed for the days when I could pick him up from school, and see his smiling face running to my car. We were in the hospital for a total of 17 days. Ryan was only able to walk and get out of bed 3 days prior to that. When we were finally released from the hospital Ryan was extremely pale. He came out looking skeletal due to the fact that he couldn’t eat and was already only 39 pounds before falling ill. He had to be on a strict regimented low sodium diet for his kidneys and wasn’t able to do any physical activity, so I homeschooled Ryan for the remainder of his school year. He still had temperament issues and one time had an episode so bad I was worried he was going to injure himself. He was screaming, throwing things, breaking things, I would try to go talk to him and he would hit me. I sat outside on the back porch and cried, while he continued to scream and yell in a fit of rage. I didn’t even recognize my own child, so the doctor requested a brain MRI to ensure he didn’t have any permanent brain damage from the HUS.

I am a flight attendant and I have worked for 5 years. Going back to work was the hardest thing I ever had to do. I tried to return back to work in July, but I was suffering from severe anxiety. I would have major panic attacks, I wasn’t able to sleep or eat. I couldn’t stand the thought of having to be separated from Ryan or the fear of something happening to him, so I had to get prescribed anti-anxiety medication and go to therapy for my feelings and thoughts. Ryan and I had to move back in with my parents because of the income I lost, and I am still in October trying to get back on my feet financially due to all the time I took off work. This illness was devastating to us. I wish I could have traded places with Ryan as no innocent 6-year-old child should ever have to experience what he did.

I didn’t know that there was an E. coli outbreak at the time I had purchased or served him the salad, and I definitely was not prepared for the absolutely devastating impact it had and continues to have on our lives.

The causal link between Ryan Buban’s confirmed E. coli O157 infection and romaine lettuce that he consumed from Papa Murphey’s Pizza is clear. Ryan ate contaminated romaine lettuce in a salad from Papa Murphey’s Pizza located in Rocklin, California on April 10, 2018.

Ryan began to experience symptoms consistent with E. coliinfection on April 12, 2018. An exposure on April 10 is consistent with a Shiga toxin-producing E. coli (STEC) incubation period that can range from 1 to 10 days. A stool specimen collected on April 15, 2018 tested positive for E. coli O157 at Roseville Medical Center in Roseville, California. Further testing at the California Department of Public Health indicated that Ryan’s PFGE results match the nationwide outbreak associated with lettuce (PFGE Pattern: EXHX01.0047/EXHA26.0626).

Given Ryan’s confirmed infection with E. coli O157,his exposure to romaine lettuce within the given STECincubation period, and the genetic evidence connecting his infection to the outbreak (Outbreak ID 1804MLEXH-1), Ryan was identified as a confirmed case in the outbreak by the California Department of Public Health.

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[1]          “Peritoneal signs” include, rebound tenderness, tenderness to percussion, and involuntary guarding. “Abdominal Examination.” Overview, Preparation, Technique, 15 Nov. 2017, emedicine.medscape.com/article/1909183-overview.

[2]          Reference ranges for this lab: WBC 4.5-13.5K, hemoglobin 11.5-14.5 g/dL, hematocrit 33-45%, platelets 150-400 K/uL, BUN 6-25 mg/dL, creatinine 0.50-1.10 mg/dL, AST 10-47 U/L, total bilirubin <1.1, lipase 73-393 U/L, CRP 0-9.0 mg/L

[3]          Intussusceptionis the slipping of one part of an intestine into another part just below it; becoming ensheathed. Although it is an infrequent cause of bowel obstruction in adults, it is the most common cause in infants and usually occurs in the ileocecal region of the bowel. Prognosis is good if surgery is performed immediately, but mortality is high if this condition is left untreated more than 24 hr. Venes, Donald. Taber’s Cyclopedic Medical Dictionary (Taber’s Cyclopedic Medical Dictionary (Thumb Index Version)) (Page 1287). F.A. Davis Company. Kindle Edition.

[4]          Ascitesis an accumulation of serous fluid within the peritoneal cavity. It is the most common complication of liver cirrhosis. In children, hepatic, renal and cardiac disorders are the most common causes. Bavdekar, A, and N Thakur. “Ascites in Children.” Indian journal of pediatrics., U.S. National Library of Medicine, Nov. 2016, www.ncbi.nlm.nih.gov/pubmed/27278239

[5]          Increased blood levels of CRP are present in many infectious and inflammatory diseases (including in patients with coronary artery disease, in whom it is sometimes employed as a risk factor). CRP levels are sometimes monitored serially to determine if infectious or inflammatory diseases have been effectively treated. Venes, supraNote 85 at 1926.

[6]          On 5/27/18, the state lab confirmed E. coliO157:H7

[7]          Oliguria is defined as a urine output that is less than 1 mL/kg/h in infants, less than 0.5 mL/kg/h in children, and less than 400 mL daily in adults. It is one of the clinical hallmarks of renal failure and has been used as a criterion for diagnosing and staging acute kidney injury (AKI), previously referred to as acute renal failure. https://emedicine.medscape.com/article/983156-overview

[8]          Erythropoietin (also known as EPO) is a growth factor that stimulates the production of red blood cells. Most of the cells in the blood are red blood cells, whose main function is to carry oxygen throughout the body. https://www.themmrf.org/multiple-myeloma-knowledge-center/myeloma-treatments-guide/growth-factors/erythropeietin/