Daniela Arias Rodriguez

Internal Medicine H&P #1  7/7/20

 Identifying Data:

Name: Mr. E

Address: Queens, NY

Date of Birth: 73 yrs old

Date & Time: July 7, 2020

Location: NYPQ

Source of Information: Self

Source of Referral: PCP

Chief complaint: fever and dark urine x 2 days

HPI:Mr. E  is a 73 y/o 16 pack per year Hispanic male with PMHx of HLD and PSHx inguinal hernia repair was referred to ED of NYQP on 7/6 from an urgent care with complaints of fever and dark urine x 2 day. Pt reports that the day prior he experienced generalized body ache accompanied by nausea and a vomiting episode. Vomitus was non-bloody and bilious in appearance. Pt reports normal bowel movements and decreased appetite on 7/6. Pt denies abdominal/pelvic pain, painful urination, chest pain, palpitations, chills, SOB, headache, cough, sore throat, rhinorrhea, loss of taste/smell, sick or COVID positive contact or recent travel. ED work-up showed elevated cancer markers Ca 19-9 (39.8) and CEA (2.4), LFTs and bilirubinemia (2.7). Pt was given ceftriaxone and metronidazole for suspected cholangitis. Abdominal US showed possible cholelithiasis or neoplasm. CT scan showed an irregular lesion near the neck of the gallbladder. Pt was admitted for further work-up due to suspected gallbladder mass or cholangitis.

Currently, pt is A&O x3, NPO, afebrile, with no abdominal/urinary complaints or apparent distress. As per patient, urine color has returned to nearly normal (yellow color). Pt reported decreased yellow discoloration of the skin and sclera. Pt was continued on ceftriaxone IV 1000mg q24h. As per GI consult, Pt was sent for an MRI of the abdomen which showed a few stones in the gallbladder and possibly impacted stones in the common bile duct. Pt was also sent for an EGD and ERCP which showed small hiatal hernia/gastritis and multiple stones in the gallbladder with no abnormalities in the common bile duct, liver and common hepatic ducts, respectively. Pt was scheduled for laparoscopic cholecystectomy on 7/10 and was kept under the surgery services after procedure.

Past Medical History:

Present illnesses – Denies

Past medical illnesses –Right inguinal hernia repair, year

Hospitalized – (see PSHx).

Immunizations -unknown status. Received Pneumococcal 23-valent vacc under service.

Colonoscopy- never had a colonoscopy.

Past Surgical History:

Right inguinal hernia repair, no complications-unknown year

Medications:

Vitamins

Allergies:

No allergies

Family History:

Father: Leukemia, deceased of unknown cause.

Social History: Mr. E is a retired 16 pack per year smoker who lives with his wife and daughter. Pt is ADLs independent.

ROS:

Gen –Denies loss of appetite, fatigue, weight loss, fever, chills or night sweats.

Skin, hair, nails—Denies change in texture, dryness, pruritus, diaphoresis or change in hair distribution.

Head—Denies headache, vertigo, light-headedness or recent head trauma

Eyes—Denies blurring vision, photophobia, pruritus, dryness, diplopia, scotoma, lacrimation, halos or fatigue with use of eyes. Use glasses occasionally. Unknown last eye exam

Ears— Admits a slight hearing difficulty bilaterally, which he attributes to age. Denies use of hearing aids, pain, discharge or tinnitus.

Nose/sinuses—Denies epistaxis, nose discharge or obstruction.

Mouth/throat—Admits use of dentures. Denies bleeding gums, sore tongue, sore throat, mouth ulcers, or changes in voice. Unknown last dental exam.

Neck—Denies localized swelling, lumps, stiffness or decreased range of motion

Pulmonary – Denies dyspnea, cough, orthopnea, dyspnea, hemoptysis or wheezing.

CV—Denies HTN, chest pain, peripheral edema, syncope, palpitation, irregular beats and known heart murmur.

GI—Admits feeling nauseous and having a vomiting episode x 2 days ago. Reports decrease appetite on 7/6. Pt admits yellowish skin and eyes bilaterally since 7/5. Denies diarrhea, constipation, abdominal pain, dysphagia, hematemesis, hemorrhoids, heartburn or change in BM. Pt has never had a colonoscopy.

GU— Admits dark urine since 7/5. Denies frequency, nocturia, urgency, oliguria, dysuria, polyuria, hesitancy, incontinence or dribbling. Admits having a prostate exam a while ago, unknown results.

Nervous— A&O x3. Denies seizures, headache, loss of consciousness, numbness, paresthesias, dysesthesias, ataxia, loss of strength and change in cognition or memory.

Musculoskeletal—Denies muscle pain, swelling, redness, deformity of muscles/ joints or arthritis.

Peripheral— Denies intermittent claudication, coldness, varicose veins, peripheral edema and color change.

Hematological—  Denies hx of blood transfusion, anemia, easy bruising, lymph node enlargement or Hx of DVT/PE.

Endocrine—Denies polyuria, diaphoresis, polydipsia, polyphagia, heat or cold intolerance, goiter and hirsutism.

Psychiatric— Patient denies depression or suicidal ideations.

VS:T 37.0 C, HR 78 bpm, BP 149/85 right arm lying in bed, RR 16, SpO2 100% room air, BMI 24.9, Glucose: 134 (morning).

Physical Exam:

Gen– AOx3, no apparent distress, average build and appears his stated age.

Skin: warm & moist, good turgor, slightly icteric, no visible lesions, scars or tattoo.

Nails: no signs of clubbing, lesions, paronychia, capillary refill <2 second.

Hair: Evenly distributed with no signs of erythema or dryness in the scalp. Thick hair texture.

Head:No specific facies. Normocephalic, non-tender to palpation with no signs of swelling or trauma.

Ear: Intact tympanic membrane with undisturbed cone of light bilaterally. No lesions or erythema in the auditory canal bilaterally. Whispering test unremarkable bilaterally.

Eyes:slightly icteric sclera and pink conjunctiva bilaterally. PERRL, full visual fields and intact EOM with no nystagmus. Visual acuity to counting fingers. Unremarkable optic disc, no hemorrhage or exudates bilaterally on fundoscopy.

Mouth: pink and moist mucosa with no masses, thrush or lesions. No signs of tonsil exudate or enlargement. Uvula pink with no signs of edema, deviation or lesion. Use of denture.

Trachea/thyroid:midline and non-tender to palpation. Non-palpable nodule or bruit on auscultation. No lymphadenopathy.

Lungs:  Clear to auscultation bilaterally. No rales, rhonchi or wheezing on auscultation. No signs of labored breathing. Unremarkable egophony and tactile fremitus.

Cardiac:Normal S1/S2 and RRR. No murmur, JVD or carotid bruits noticed.

Abdomen:Bowel sound present in all 4 quadrants and non-tenderness to palpation. No guarding or rebound tenderness. No signs of distention, ascites, striae, scars or mass. No signs of liver or spleen enlargement. Negative Murphy’s sign.

GU:  Descended testicles bilaterally, no penile lesion or discharge or hernia.

Rectal:. No lesions, fissures, hemorrhoids or stool in rectal vault. Good sphincter tone. Negative guaiac.

Extremities:  Full passive and active ROM in upper and lower extremities bilaterally. 2+ pulses in upper and lower extremities. No sign of edema, cyanosis or muscle atrophy. Neurology: A&O x 3. Intact finger to nose test. Intact rapid alternating movement and heel-to-shin test. Intact sensation, and proprioception in UE and LE bilaterally.  Unremarkable gait and negative Romberg test. Muscle strength 5/5 in UE and LE. Cranial intact 2-12. No signs of asterixis. Biceps, ankles and triceps reflexes 2+ bilaterally. Intact cranial nerves II-XII.

DDX:

• Gallbladder cancer
• Pancreatic cancer
• Cholangitis
• Cholecystitis
• Cholelithiasis
• Viral hepatitis

Assessment/plan:  Mr. E is a 73 y/o Hispanic male with PMHx of HLD and PSHx inguinal hernia repair was referred to ED of NYQP on 7/6 from an urgent care with complaints of fever and dark urine x 2 days. Painless jaundice, elevated LFTs, MRI and ERCP findings indicating cholelithiasis.

#Cholelithiasis:

–AST 124 on 7/6 to 51 on 7/10

ALP 135 on 7/6 to 117 on 7/10

ALT 99 on 7/10

Total bilirubin 4.6 on 7/6 to 1.4 on 7/10

CA 19-9 39.8

CEA 2.4

-GI consult

-Surgery consult

-MRI: multiple stones in gallbladder with no signs of masses. Abrupt narrowing of distal common bile duct

-ERCP: multiple stones in gallbladder with no abnormalities in the common bile and hepatic ducts.

-No signs of gallbladder wall thickening or pericholecystic fluid on imaging less likely cholecystitis.

-Painless jaundice on admission.

-Perform daily LFTs, CBC and electrolytes.

-Continue ceftriaxone IV Inj 1000mg q24h.

– Monitor daily I&Os and quality of urine.

-Keep the patient on a clear liquid diet. Place pt on NPO starting 7/9 @ 12:00am for surgery.

-provide referral to GI outpatient for colonoscopy to rule out malignancy. Elevated CEA and CA 19-9.

# Aneurysmal ascending in thoracic aorta:

-chest x-ray performed on 7/9 showed mild prominence R. heart border probably due to “ectatic or aneurysmal thoracic aorta.”

-ECG showed sinus bradycardia. No other findings. Pt’s HR ranges in the low 60s.

-provide cardiology referral upon discharge.

# Gastritis/ hiatal hernia:

-provide GI referral upon discharge.

-Currently, pt denies heartburn, chest pain, regurgitation or other GI complaints.

#DVT prophylaxis:

-administer 40MG of Enoxaparin Inj daily.

#COVID:

–Denies any sick or COVID positive contact. Denies loss of taste/smell, cough, sore throat, body aches or headache. CXR showed no lung infiltrates. Negative COVID swab.

 

Article Summary: Case Report, 2018

 A woman with abdominal pain, jaundice and elevated CA 19.9 Alessandra Fusco, Francesca Baorda, Lorenzo Porta,  Alessandro A. Lemos, Lucio Caccamo, Eleonora Tobaldini, Giorgio Costantino

• This is a case report of 54 y/o female who presented with severe epigastric/hypochondrial pain radiating to the back, weight loss, jaundice (for 3 days) and hyperchromic urine (for 7 days)
• Patient was sent for an abdominal Ultrasound that showed distended gallbladder with wall thickening with no calcific gallstones. Abdominal US also showed dilation of intra/extrahepatic bile ducts and common bile ducts and hyperechogenic material concerning cholangiocarcinoma.
• Blood work showed elevated hepatic markers such as SGOT, SGPT, total bilirubin, conjugated bilirubin and C-reactive protein with normal CBC and electrolytes.
• Carbohydrate antigen (CA 19-9) was found to be 9606.00 IU/ml (reference range 0-27)
• CT of the abdomen was formed which showed stones in calcified gallstone infundibulum and common bile duct.
• Because of the contradicting findings in the US and CT, PET imaging was considered which results did not indicate malignancy.
• An endoscopic US showed dilation of common bile duct and biliary sludge at the cystic and common hepatic duct. A biliary stone was localized at the common bile duct near the ampulla of vater. Multiple gallstones were visualized in the gallbladder without any vascularization. EUS confirmed the absence of malignancy and suggesting cholelithiasis of this patient.
• Regardless of the US findings suggesting a possible mass, CT, PET and EUS did not demonstrate presence of a mass. ERCP was performed and stones were removed, two in the common bile duct and infundibulum of the gallbladder.
• After 5 days of procedure, level of CA 19-9 dropped to 600 U/ml.
• Specimen study did not show presence of malignancy.
• After 3 months, CA 19-9 level was 12.5 U/ml.
• It was concluded that high levels of CA 19-9 can be produced by the epithelium of the biliary duct to be eventually secreted into the biliary system. When obstruction of the biliary tract occurs, enhancement of secretion and movement of this cancer marker into the bloodstream occurs. Elevation of this cancer marker does not always indicate malignancy.

Article Pdf: fusco2018

End of Rotation Self-reflection: RT-3 Internal Medicine

• What was a memorable patient or experience that I’ll carry with me? In this rotation, I saw very ill patients with multiple complications and diseases. Some of the patients were in the units for a few days or weeks and others for almost two months. During my first week, I saw a Hispanic lady with alcoholic cirrhosis, encephalitis, ESRD, hx of cardiac arrest and other PMHx. She was admitted to the hospital due to acute respiratory failure and was placed on ventilation. I was following this patient almost daily, since my first week on the rotation. Therefore, I got to build some rapport with the patient and her mother, which both speak Spanish only. Patient was bedbound, constantly complaining of pain, very cachectic and unable to communicate, unless through the mother. During the last week of rotation, it was very rewarding to see her out of bed receiving physical therapy, not as cachectic and even smiling. Before I was debating between internal medicine and emergency medicine, but I would like to build a rapport with my patients and witness their progress like I did with this lady. These moments add meaning to our practice, and I think that internal medicine can offer that.
• Skills or situations that are difficult for you (e.g. presentations, focused H&Ps, performing specific types of procedures or specialized interview/pt. education situations) and how you can get better at them During this rotation, I was able to practice a lot of ABGs and venipunctures. I was very successful when performing the ABGs and that made me feel confident about the technique that I was using. However, I noticed that I need to improve my venipuncture technique, especially when palpating for not visible veins and performing these in non-elderlies. I had the opportunity to assist a phlebotomist for two days in the morning, and this was one of the areas that she highlighted as well. I also performed a NG tube, however, it was completed by the PA. In this patient, it was a little bit difficult to advance the NG tube, because the patient couldn’t swallow. In patients unable to follow commands, the PA advised me to advance the NG tube between breaths. Despite the unsuccessful procedure, I was glad to have that hands-on experience of placing an NG tube. I’m looking forward to keep practicing these procedures in upcoming rotations, particularly ER.
•  What do you want to improve on for the following rotations? What is your action plan to accomplish that?As mentioned previously, I need to improve my venipuncture techniques as well as get more hands-on when performing NG tube, IV access and urinary catheter procedures. Aside from these areas of improvement, I need to develop a more comprehensive assessment and plan. I noticed this is a very important skill in internal medicine that I felt weak. In order to improve, I need to get myself more involved in doing this task in upcoming rotations and learn from the feedback.

Evaluation reflection In this site evaluation, I presented a 73 y/o 16 pack year Hispanic male with non-significant pMHx complaining of fever and dark urine x 2 days. Initial imaging work-up was concerning for gallbladder mass or cholangitis. Pt also had elevated cancer markers Ca 19-9 and CEA. Pt was sent for an MRI of the abdomen which showed a few stones in the gallbladder and possibly impacted stones in the common bile duct, however, ERCP confirmed no abnormalities in the common bile duct, liver and common hepatic ducts. Pt was scheduled for laparoscopic cholecystectomy. Overall, I received a good feedback from Mr. Combs. As per Mr. Combs, my presentation was organized and well-prepared. This was a patient that I was following almost daily from his admission to his discharge, so I knew him very well. Mr. Combs encouraged me to keep practicing and improving my presentation skills.

Typhon Report

IM typhon

Mini-CAT

Are antibiotics effective as an appendectomy at treating uncomplicated appendicitis in adults older than 18 years old?

 Scenario: Acute appendicitis is the most common cause of acute abdomen and the most common emergent surgical procedure related to the abdomen. It has a lifetime risk of 8.6 % and 6.9 % in males and females, respectively. It typically presents with right lower quadrant abdominal pain, anorexia, nausea and vomiting. Uncomplicated appendicitis is indicated by absence of perforation on imaging results such as inflammatory mass, phlegmon or abscess. The first line treatment for uncomplicated appendicitis is open or laparoscopic appendectomy;  however, antibiotics therapy can be considered in certain cases. Therefore, I would like to investigate if antibiotic therapy can be as effective as appendectomy at treating uncomplicated appendicitis.

 Question: Are antibiotics effective as an appendectomy at treating uncomplicated appendicitis in adults older than 18 years old?

Question Type: What kind of question is this? (boxes now checkable in Word)

☐Prevalence               ☐Screening                   ☐Diagnosis

☐Prognosis                  ☐Treatment                ☐Harms

PICO search terms

P	I	C	O
Adults > 18 y/o	antibiotic therapy	appendectomy	higher effective rate
Uncomplicated appendicitis	antibiotic management	open appendectomy	higher effectiveness
Unperforated appendix	non-operative management	laparoscopic appendectomy	lower recurrence
	conservative management	surgical management	lesser readmission

 Search tools and strategy used:

 Pubmed:

Appendectomy and Antibiotics for uncomplicated appendicitis–> 1,345

Appendectomy and Antibiotics for uncomplicated appendicitis–>(best match, 5 years, RCT, meta analysis, systematic review, full text) –>52

Google Scholar:

Appendectomy and Antibiotics for appendicitis–>22,900 –>(filter 2010-2020) → 14,600

Cochrane Library :

Appendectomy and Antibiotics for uncomplicated appendicitis–>(filter 2010-2020)–> 1 cochrane review and 54 trials.

I started my search on Pubmed using the terms “Appendectomy and Antibiotics for uncomplicated appendicitis,” since these are the two interventions of interest. After applying the filters, I was able to find numerous meta analysis and systematic reviews published in 2019 and 2020. It seems that this is a topic currently being studied. Some of the meta-analyses and systematic reviews were performed on the pediatric population or were addressing only one intervention. I also found a few studies that were done on exactly the same articles. For example, I found two meta analyses that included the same randomized controlled trials, but were published one year apart. Therefore, I kept the most recent meta-analysis. I continued my search in Google Scholar and Cochrane library, but I was not as successful as in Pubmed. In the Cochrane Library, I found a review published in 2011; however, it was inaccessible and not as recent as the selected systematic-reviews and meta analysis. These meta analyses and systematic-review were published outside of the United States; however, some of the included randomized controlled trials were performed in the USA and in other places across the world. Regardless of place of publication, the selected studies were among the most recent and available studies addressing the two interventions in patients with uncomplicated appendicitis. In addition, as mentioned previously, some studies were addressing the children population or focusing on one intervention only.

Chosen Articles:

1. Podda, M., Gerardi, C., Cillara, N., Fearnhead, N., Gomes, C. A., Birindelli, A., . . . Saverio, S. D. (2019). Antibiotic Treatment and Appendectomy for Uncomplicated Acute Appendicitis in Adults and Children. Annals of Surgery,270(6), 1028-1040. doi:10.1097/sla.0000000000003225
2. Yang, Z., Sun, F., Ai, S., Wang, J., Guan, W., & Liu, S. (2019). Meta-analysis of studies comparing conservative treatment with antibiotics and appendectomy for acute appendicitis in the adult. BMC Surgery,19(1). doi:10.1186/s12893-019-0578-5
3. Poprom, Napaphat, et al. “The Efficacy of Antibiotic Treatment versus Surgical Treatment of Uncomplicated Acute Appendicitis: Systematic Review and Network Meta-Analysis of Randomized Controlled Trial.” The American Journal of Surgery, vol. 218, no. 1, 2019, pp. 192–200., doi:10.1016/j.amjsurg.2018.10.009.
4. Rollins, Katie E., et al. “Antibiotics Versus Appendicectomy for the Treatment of Uncomplicated Acute Appendicitis: An Updated Meta-Analysis of Randomised Controlled Trials.” World Journal of Surgery, vol. 40, no. 10, 2016, pp. 2305–2318., doi:10.1007/s00268-016-3561-7.

Evidence Retrieved

Poddo, Mauro et al, 2019

Level of evidence: Systematic review and meta-analysis

Sample/Settings:

• Sample size: This systematic review and meta-analysis included twenty studies with a total sample size of 3,618 patients. Seven of these studies were RCTs, eight prospective cohorts, four retrospective cohorts and one a quasi randomized study. These studies compared antibiotic therapy to surgical therapy appendectomy in patients with uncomplicated appendicitis. The antibiotic group consisted of 1743 participants and the surgical group of 1875 participants.
• Inclusion criteria: Randomized controlled trials, prospective and retrospective cohort studies comparing antibiotic therapy versus surgical treatment for uncomplicated appendicitis and reporting at least one of the primary/secondary outcomes were eligible for inclusion in the analysis. Studies including adults or children also met the inclusion criteria.
• Exclusion criteria: Studies were excluded if outcomes of interest were not reported, or participants selection criteria was not clear. Studies reporting complicated appendicitis or specifying the antibiotic regimen were also excluded as well as studies not reporting absolute numbers or odd ratios. Review articles, letters, case reports or comments were subjected to exclusion.
• Primary Outcomes:included complication-free treatment success, treatment efficacy within 1 year follow-up, post-intervention complications, surgical complications, and complicated appendicitis with development of peritonitis at surgery.
• Secondary outcome:number and rate of patients managed with laparoscopic, total cost, quality of life, length of hospital stay and total length of stay per patient, pain duration, length of sick leave and time off work.

Key Findings:                                                                                                                                                        

• In terms of complication-free treatment success, it was found that appendectomy provided higher success rate as compared to antibiotic therapy (82.3% versus 67.2%, OR: 0.30, P<0.00001)
• In terms of treatment efficacy within 1 year follow-up, surgical therapy appendectomy had a higher success rate as compared to antibiotic therapy (93.1% versus 72.6%, OR: 0.12, P<0.00001), but with no significant difference between children and adults.
• No significant difference was found in the rate of patients undergoing laparoscopic appendectomy as first line therapy and those after antibiotic failure (P= 0.16)
• Intraoperative findings of complicated appendicitis with peritonitis was 21.7% in patients treated with antibiotic therapy versus 12.8% treated with surgery (OR: 2.01, P= 0.07). The odd ratio of developing complicated appendicitis doubled for patients treated with antibiotics and undergoing surgery after antibiotic failure.
• Complication rate was remarkably lower for patients treated with antibiotics as compared to patients managed with surgery ( 7.1% versus 14.5%, OR: 0.41, P= 0.006). Complications after surgery were more noticeable in the surgery group than in the antibiotic group, but seen only in the adult population (14.5% versus 6.6%, OR:0.39, P=0.04)
• In terms of cost, antibiotic treatment was remarkably more affordable than surgical therapy ($2509.14 versus $4898.57, P< 0.00001) with an estimated 50% reduction of cost with antibiotic therapy.
• In terms of length of hospital stay, both antibiotic and surgical therapies had similar duration of primary hospital stay (2.9 days versus 3.3 days, P= 0.25).
• There was no difference in duration of pain, length of sick leave/ time off work and total length of stay per patient between the antibiotic and appendectomy group. Analysis on quality of life could not be performed.

Limitations / Biases: This study acknowledged a significant heterogeneity among the included studies, particularly among the diagnostic criteria for uncomplicated appendicitis, type of antibiotic, duration of treatment and measured outcomes. Moreover, participants and researchers were not blinded in none of the studies, which could have introduced biases in the results.

Yang, Zhengyang et al,  2019:

Level of evidence:Meta-analysis

Sample/setting:

• Sample size: Eleven studies were included in this meta-analysis with a total sample size of 2751 participants. The appendectomy group had 1288 patients and the antibiotic group 1463 patients. Of these studies, five were RCTs, three retrospective cohorts and 3 prospective cohort studies. Participants were distributed into three subgroups uncomplicated, complicated and RCT populations.
• Inclusion criteria:Studies comparing appendectomy versus conservative treatment (antibiotics and other conservative measures) in adults patients with diagnosed or suspected acute appendicitis were included in the meta-analysis. Studies published in English or Chinese were considered for eligibility. Inclusion criteria was not limited to type/duration of antibiotic, and surgical technique (open or laparoscopic).
• Exclusion criteria:Studies were excluded if they were published prior to 1990 or were case reports, editorials, reviews, pediatric studies, single-arm or used non-pertinent diagnostic studies.
• Primary outcomes: included effective rate, recurrent of appendicitis, and mortality.
• Secondary outcomes:included length of hospital stay/sick leave and morbidity related to antibiotic or surgical treatment such as surgical site infection, incisional hernia/pain, obstructive symptoms, abscess, wound dehiscence, bladder dysfunction, diarrhea, abdominal pain/discomfort.
• Conservative management included antibiotic therapy and other conservative measures. Six studies used non-antibiotic conservative management such as waiting for improvement within 24 hrs and proceeding with appendectomy if improvement did not occur.

Key Findings:

• In terms of treatment effectiveness, there was a remarkable reduction with conservative therapy as compared to appendectomy. Conservative treatment had an overall effective rate of 82.8. As per the uncomplicated population, treatment effectiveness was 95.2%.
• As compared to the appendectomy group, the incidence of complication was lower in all subgroups treated with conservative management (OR: 0.22-0.51). The rate of complication among all patients treated with conservative approach was 10.3%. As per the uncomplicated subgroup, the complication rate was 3.5.
• The reoperation rate was lower for patients undergoing emergency appendectomy as compared to patients treated with conservative treatment (OR: 9.58-14.29). The reoperation rate for patients in the conservative group was 5.6% and as per uncomplicated subgroup 7.0%.
• The overall length of stay was 0.47 days longer in the conservative group than in the surgical group.

Limitations/ Biases: Due to the nature of the intervention, participants and researchers were not blinded in any of the studies. Across the studies, follow-up period ranged from 60 days to 1 year and in some studies it was not clearly defined; therefore, results of treatment efficacy should be interpreted cautiously. Aside from variability in follow-up length, different antibiotic therapies were used across the studies as well as other conservative methods possibly affecting results in the conservative group. This meta-analysis acknowledged other variables that could have affected outcomes of therapy such as white blood cells, C-reactive protein, BMI, and severity of symptoms. This study could not account for time from diagnosis to treatment, which might have affected outcome of treatments.

 Poprom, Napaphat et al 2019

Level of evidence:Systematic Review and Network of Meta-analysis

Sample/setting:

• Sample size: Nine RCTs were included of which two were done on children, six on adults and one on mixed population. Total sample size of the nine RCT was not clearly stated, but the network meta-analysis was done on seven RCTs with a total sample size of 2017 participants. Participants had a mean age range from 18.5- 38 years. In all the studies, the follow-up period was for 12 months.
• Inclusion criteria:RCTs published in English comparing antibiotics with open or laparoscopic appendectomy were eligible for inclusion. Studies performed on children or adults diagnosed with uncomplicated appendicitis were also inclusion criteria. Eligible studies should have reported at least one of the outcomes of interest such as treatment success, overall complications, recurrence and length of stay.
• Intervention:Antibiotic interventions were 3rd generation cephalosporin plus metronidazole/tinidazole, beta-lactamase plus metronidazole/tinidazole, beta-lactamase plus penicillin, beta-lactamase inhibitor and penicillin. The antibiotic groups were compared to open or laparoscopic appendectomy
• Primary outcomes: included initial treatment success, recurrence and overall complications.
• Secondary outcomes:included recurrence of appendectomy after initial treatment and length of stay during primary hospital admission.

Key Findings:

• Overall, antibiotics had non-significant reduced treatment success as compared to appendectomy (pooled RR 0.68 and 0.88). Although, according to SUCRA, the probability of surgery being the best treatment was 89.9 followed by beta-lactamase plus penicillin and beta-lactamase inhibitor 61.9 and 50, respectively.
• In terms of specific antibiotics, beta-lactamase plus pen and beta-lactamase inhibitor were found to be better than cephalosporins plus metronidazole and penicillin alone.
• In terms of complicated appendicitis after surgery, it ranged from 2.7% -35% with antibiotics and 1.5%-60% with appendectomy.
• Beta-lactamase and Cephalosporins plus metronidazole had remarkably lower risk of complications as compared to appendectomy (RR 0.14 (0.05, 0.37) and 0.35 (0.16, 0.75), while penicillin had three times higher risks of complications (RR 2.98 (0.29, 30.36)
• Significant higher risks of recurrence were noticed with antibiotics as compared to appendectomy (pooled RR 12-87) with penicillin having the highest risk. Surgery had the lowest risk of recurrence followed by cephalosporins plus metronidazole.
• In terms of length of stay, beta-lactamase had the shortest length of stay followed by surgery.

Limitations/Biases:

• This study acknowledged heterogeneity among the studies particularly among definitions of outcomes such as treatment success, complication and recurrence. Moreover, patients’ population was different from study to study. In addition, it was not clearly stated how RCTs diagnosed uncomplicated appendicitis (imaging or clinical diagnosis) possibly affecting treatment efficacy.

 Rollins, Katie et al 2016

Level of evidence:meta-analysis

Sample/settings:

• sample size: This study included five RCTs with a total sample size of 1430 participants. The antibiotic group consisted of 727 participants and the appendectomy group of 703 participants.
• Inclusion criteria: Studies were eligible for inclusion if they were carried out on adult patients diagnosed with uncomplicated appendicitis and treated with antibiotic or appendectomy. Studies reporting at least one post-intervention outcome were eligible for inclusion.
• Exclusion criteriaStudies were excluded if they were performed on pediatric patients or on patients with complicated appendicitis or if they were not randomized controlled trials.
• Primary outcomes: included post-intervention complications.
• Secondary outcomes: included length of stay, readmission rate, treatment efficacy, pain, need of analgesics, perforation after intervention and temperature

Key findings:

• In terms of overall treatment efficacy at 1 year follow-up, appendectomy was found to have higher efficacy with 88.1% as compared to antibiotics with 62.6% .
• As compared to appendectomy, antibiotic therapy had a 39% risk reduction in terms of complications (RR: 0.61, P=0.002)
• In terms of length of stay, there were no remarkable differences between the antibiotic and appendectomy group (mean difference 0.25 days, P= 0.10). Although in studies that restricted cross-over of patients between treatment modalities, a shorter length of stay was found in patients treated with appendectomy (mean difference 0.39 days, P= 0.0003)
• From a total of 785 patients who had appendectomy as initial treatment, 133 had complicated appendicitis (perforation or gangrenous appendicitis) and 23 had a normal appendix.
• In terms of readmissions, 123 out of 602 patients from the antibiotic group were readmitted due to suspected recurrent appendicitis. From these readmitted patients, 120 had appendectomy and 3 were treated with antibiotic therapy.
• Two studies found antibiotics to provide fewer sick leave as compared to appendectomy, while one study found no significant difference between these treatment modalities.

Limitations/ Biases: Some of the studies were published more than 20 years ago, whose methods and results might not be as applicable to current practices. Only two studies used a high sensitivity and specificity test such as CT scan to diagnose appendicitis. The other studies relied on history and clinical findings indicating appendicitis. Moreover, studies had great variability in terms of antibiotic type, route and timing of therapy possibly affecting treatment effectiveness. One study administered oral antibiotics as the first line treatment, but used IV antibiotics for patients experiencing nausea and vomiting.

 Conclusion(s)

Poddo, Mauro et al, 2019: This study found that antibiotic therapy as initial non-surgical management for uncomplicated appendicitis has a treatment failure of 27.7% at 1 year follow-up, lower complication-free treatment success rate (67.2% versus 82.3%, P<0.0006) and twice the incidence of complicated appendicitis when surgery is delayed as compared to appendectomy. Antibiotic therapy was found to have reduced rate complications related to therapy and lower treatment cost. Antibiotic therapy was remarkably more affordable than surgical treatment ($2509.14 versus $4898.57, P< 0.00001). Differences among duration of pain, length of hospital stay/sick leave/ time off work and complication after surgery were not significant between the groups. This study found that development of peritonitis is not a significant risk when a course of antibiotics is tried.

Yang, Zhanyang et al, 2019:This study concluded that conservative therapy, which includes antibiotics, has high efficiency at treating acute appendicitis in adult patients; however, it is still lower than appendectomy. Antibiotics were found to have lower incidence of complications as compared to emergency appendectomy. Appendectomy was found to have higher effective treatment rates as well as lower reoperation rate. Temporary antibiotic therapy can be considered in patients who strongly refuse surgery; although, risk of recurrence and possible need for future operation should be highlighted as well as higher rate of reoperation.

Poprom, Napaphat et al 2019: This study concluded that antibiotics therapy is associated with 12%-32% lower treatment success at 1 year as compared to appendectomy; however, antibiotic therapy had 23%-86% lesser complications. Appendectomy provided the best treatment success followed by beta-lactamase with or without penicillin, while beta-lactamase and cephalosporins plus metronidazole were the second best in lowest complications. In non-surgical candidates, beta-lactamase with or without penicillin can be the first line antibiotic for treating uncomplicated appendicitis. Beta-lactamase with or without penicillin were found to provide lower complications and recurrence rate as compared to the other antibiotics. In all outcomes, penicillin alone was found to be inferior as compared to surgery and other antibiotics.

Rollins, Katie et al, 2019:This study found that antibiotic therapy is a secure, effective and feasible treatment option for uncomplicated acute appendicitis. Antibiotic therapy was found to be 41.1%-78.5% effective as compared to appendectomy which was 85%-100% effective at treating appendicitis. Antibiotic therapy was associated with a significant reduction in complications after operation. In terms of length of stay and risk of developing complicated appendicitis, no significant difference was found between the groups.

All four studies agreed that appendectomy is still superior to antibiotic therapy at treating uncomplicated appendicitis in adult patients. This correlates with current guidelines established by the American College of Surgeons, the Society of American Gastrointestinal and Endoscopic Surgeons, the European Association of Endoscopic Surgery and the World Society of Emergency Surgery which recommended appendectomy as the first line treatment for nonperforated appendicitis. Appendectomy was also associated with lower reoperation rates and recurrence within 1 year. Although antibiotics provide certain advantages such as lower incidence of treatment complications and lower healthcare cost. Antibiotic therapy was remarkably more affordable than surgical treatment.  In terms of other parameters measured (length of hospital stay, sick leave, time work off, etc), the studies found mixed results, and therefore is not clear the superiority or inferiority of appendectomy over antibiotic therapy. Only one study compared effectiveness among antibiotics recommending beta-lactamase with or without penicillin as the second best choice for treating uncomplicated appendicitis in patients refusing surgery. In conclusion, for adults older than 18 y/o with nonperforated appendicitis, appendectomy seems to be the most appropriate treatment due to its high effectiveness and lower reoperation rate and recurrence. Antibiotic therapy might be considered for non-surgical candidates or for patients refusing appendectomy.

 Clinical Bottom Line:

Weight of the evidence

I weighed the articles in the following order Poddo, Mauro >Yang, Zhanyang> Poprom, Napaphat >Rollins, Katie

Poddo, Mauro carries the heaviest evidence of my conclusion for being a systematic review and meta-analysis published fairly recently, in 2019. This study included 20 studies with a total sample size of 3618 participants having the larger sample size among the four studies. Although this study was not published in the United States, it was one of the few articles with high level evidence addressing this topic. This study directly compared the interventions of interest and the target population.

Yang, Zhanyangis weighed secondly, since it is a meta-analysis of eleven studies. This meta-analysis was also published fairly recently, 2019. Moreover, it had a reasonable sample size of 2751 participants. Although this analysis was not done in the USA, it included two studies performed in the United States. This study compared conservative therapy, which included antibiotics and watchful waiting, to appendectomy in patients with acute appendicitis. In this study, participants were further classified into three subgroups of complicated, uncomplicated and RCTs, which still includes the population of interest. It is worth mentioning that some of the studies included in this analysis were also included in the study done by Poddo, Mauro et al.

Poprom, Napaphat is systematic review and network meta-analysis of nine RCTs recently published in 2019. The network meta-analysis was done on seven RCTs with a total sample size of 2017 participants. The overall population size of the nine RCTs was not directly stated. Although this study incorporated RCTs performed on children, it also included RCTs performed on the adult population. Most importantly, this study compared effectiveness of appendectomy to antibiotics at treating uncomplicated appendicitis. This study was also published outside of the USA, but it included two studies performed in the United States. It is worth mentioning that studies included in this analysis were also incorporated in the previous mentioned studies.

Rollins, Katie is a meta-analysis of five RCTs with a total sample size of 1430 participants, which is certainly smaller than the three previous studies. Moreover, this meta-analysis was published in 2016, which is not as recent as the previous mentioned studies. This study compared antibiotics to appendectomy in patients with uncomplicated appendicitis, which addressed the intervention and population of interest. It is worth mentioning that some of the studies included in this analysis were also incorporated in the previous mentioned studies.

 Magnitude of any effects

 Poddo, Mauro:At 1 year follow-up, surgical therapy appendectomy had a higher success rate as compared to antibiotic therapy (93.1% versus 72.6%, OR: 0.12, P<0.00001), but with no significant difference between children and adults. Appendectomy was also have to higher complication-free treatment success as compared to antibiotics ((82.3% versus 67.2%, OR: 0.30, P<0.00001)

Yang, Zhanyang:Conservative treatment was found to have an overall effective rate of 82.8, although less effectiveness than appendectomy. Treatment effectiveness was 95.2% in the uncomplicated population.

Poprom, Napaphat:As compared to appendectomy, antibiotics had non-significant reduced treatment success (pooled RR 0.68 and 0.88). Although, according to SUCRA, the probability of surgery being the best treatment was 89.9 followed by beta-lactamase plus penicillin and beta-lactamase inhibitor 61.9 and 50, respectively.

Rollins, Katie: At 1 year follow-up, treatment efficacy of appendectomy was found to be higher as compared to antibiotics ( 88.1% versus 62.6%).

 Clinical significance(not just statistical significance). These two interventions, appendectomy and antibiotic therapy, were found to be effective for treating uncomplicated appendicitis; however, appendectomy is still superior to antibiotic therapy. Appendectomy not only was found to be more effective, but also was associated with lower reoperation rate and recurrence within 1 year. On the other hand, antibiotics were found to have lower healthcare cost and posttreatment complications. In adult patients older than 18 years old with uncomplicated appendicitis (without appendix perforation), appendectomy seems to be the most appropriate first line approach. Because this intervention implies removing the appendix, patients have lower risk of undergoing further surgery and recurrence of episodes as compared to antibiotic therapy in which 20% of patients have hospital readmission due to recurrence of appendicitis. If patients strongly refuse surgical management due to fear of complications or simply they are not surgical candidates, antibiotics such as beta-lactamase with or without penicillin can be an alternative to these patients. As mentioned previously, cost of antibiotics therapy is 50% lower as compared to surgical management and is certainly associated with less treatment complications.

 Any other considerations important in weighing this evidence to guide practice To guide practice, larger randomized controlled trials are needed with longer follow-up periods in order to assess long-term effectiveness. A stricter criteria is required to diagnose and classify patients as uncomplicated and complicated appendicitis. Moreover, RCTs should improve definitions of treatment success and complication.

Sources:

• https://www-uptodate-com.york.ezproxy.cuny.edu/contents/management-of-acute-appendicitis-in-adults?search=uncomplicated%20appendicitis&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#H1017040489
• https://www-uptodate-com.york.ezproxy.cuny.edu/contents/acute-appendicitis-in-adults-clinical-manifestations-and-differential-diagnosis?search=appendicitis&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2
• https://pubmed.ncbi.nlm.nih.gov/30720508/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6694559/
• https://www.americanjournalofsurgery.com/article/S0002-9610(18)30954-1/fulltext