Israel Medical Association Journal

Background: Among chronic kidney disease (CKD) patients, baseline neutrophil gelatinase-associated lipocalin (NGAL) may reflect the severity of renal impairment. No data exists on serial changes in serum NGAL levels in CKD patients before and after percutaneous coronary intervention (PCI).

Objectives: To evaluate serial serum NGAL levels relation to contrast induced acute kidney injury (CI-AKI) following PCI.

Methods: The study included 58 patients with CKD who underwent elective PCI. Plasma NGAL measurements were performed before (pre-NGAL) and 24 hours following (post-NGAL) PCI. Patients were followed for CI-AKI and changes in NGAL levels. Receiver operator characteristic identified the optimal sensitivity and specificity for pre-NGAL levels compared with post-NGAL for patients with CI-AKI.

Results: Overall CI-AKI incidence was 33%. Both pre-NGAL (172 vs. 119 ng/ml, P < 0.001) and post-NGAL (181 vs. 121 ng/ml, P < 0.001) levels were significantly higher in patients with CI-AKI, but no significant changes were detected. Pre-NGAL levels were similar to post-NGAL levels in predicting CI-AKI (area under the curve 0.753 vs. 0.745). Optimal cutoff value for pre-NGAL was 129 ng/ml (sensitivity of 73% and specificity of 72%, P < 0.001). Post-NGAL levels > 141 ng/ml were independently associated with CI-AKI (hazard ratio [HR] 4.86, 95% confidence interval [95%CI] 1.34–17.64, P = 0.02) with a strong trend for post-NGAL levels > 129 ng/ml (HR 3.46, 95%CI 1.23–12.81, P = 0.06).

Conclusions: In high-risk patients, pre-NGAL levels may predict CI-AKI. Further studies on larger populations are needed to validate the use of NGAL measurements in CKD patients.

The patient, a 32-year-old woman diagnosed with Sjögren's syndrome (SS), according to the 2016 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria, presented with paresthesia of her face and limbs. Extra glandular manifestations of her primary disease included severe Raynaud's phenomenon and chronic interstitial nephritis. There was no family history of neurologic diseases. Neurological examination was notable for symmetrical decreased sensation in the upper limbs distally. The rest of the neurological examination was unremarkable.

Fetal hydrops is a life-threatening condition defined as abnormal accumulation of fluid in two or more fetal compartments: ascites, pleural effusion, pericardial effusion, or generalized skin edema [1]. Fetal hydrops may also be associated with polyhydramnios and placental edema [2].

Based on pathophysiology results, fetal hydrops is classified as either immune or non-immune. The frequency of immune fetal hydrops has decreased dramatically since the development of Rh (D) immunization given to mothers at risk. Nonimmune hydrops fetalis (NIHF) accounts for almost 90% of cases [1]. The etiology of NIHF is further classified as cardiovascular (17–35%), chromosomal (7–16%), hematologic (4–12%), infectious (5–7%), and unknown (15–25%). Inborn errors of metabolism account for only 1–2% of NIHF cases [1]. NIHF is commonly progressive. Complete resolution of NIHF before birth is rare.

Global developmental delay (GDD), defined as a significant delay in two or more developmental domains (e.g., gross/fine motor, cognitive, speech/language, personal/social, activities of daily living), affects 1–3% of children. According to the Israeli Ministry of Health, thyroid function studies are not indicated in children with GDD unless there are systemic features suggestive of thyroid dysfunction (https://www.health.gov.il/hozer/mr36_2012.pdf). This approach also exists in other countries with newborn screening programs for congenital hypothyroidism.

We present the case of an infant with GDD, who despite normal newborn screening tests, underwent a repeated extended thyroid function analysis (including T₃ levels) leading to a diagnosis of Allan-Herndon-Dudley syndrome, a rare genetic neurodevelopmental syndrome.

Romidepsin is an intravenously administered antineoplastic agent, which acts by inhibiting histone deacetylases, thus preventing removal of acetyl groups from histones. The accrual of acetyl groups on histones causes cell cycle arrest and apoptotic cell death. It was approved for use in the United States in 2009 for treatment of refractory or relapsed cutaneous and peripheral T cell lymphomas [1-3].

The most common side effects are mild to moderate in severity and include nausea, vomiting, fatigue, fever, myelosuppression (e.g., anemia, neutropenia, thrombocytopenia), elevated liver enzymes, constipation, and rash. More severe adverse events can include marked neutropenia, thrombocytopenia, serious infections such as line sepsis, acute renal failure, tumor lysis syndrome, and cardiac arrhythmias [1].

Background: Children with forearm fractures who present to the emergency department (ED) often need a closed reduction. In our institution, until 2017, pediatric trauma patients presented to the general trauma ED (GTED) where no sedation services for pediatric patients were available. From 2017, patients presented to the pediatric emergency department (PED) where closed reductions were performed under sedation when appropriate.

Objectives: To compare GTED and PED with regard to length of stay (LOS) and hospitalization rates of pediatric patients with forearm fractures who needed a closed reduction.

Methods: Our retrospective observational study was conducted at a regional hospital. The study population consisted of all patients younger than 18 years of age who presented to the ED with a forearm fracture that needed a closed reduction. The primary outcome measure was the hospitalization rate. The secondary outcome measure was LOS in the ED.

Results: The study comprised 165 patients with forearm fractures who needed a closed reduction; 79 presented to the GTED, and 96 presented to the PED. Hospitalization rates were lower for patients undergoing closed reduction under sedation in the PED compared to the GTED (6.3% and 21.5%, respectively; P = 0.003). Median ED LOS was longer among patients undergoing sedation in the PED compared to the GTED (237 vs. 168 minutes respectively, P < 0.0001).

Conclusions: Sedation for forearm fracture reduction in a hospital’s PED was associated with a decrease of more than three times in hospitalization rate. Despite the need for more resources, PED LOS was only mildly increased.

Background: The global refugee crises have raised concerns among medical communities worldwide; nonetheless, access to healthcare has rarely been studied even though refugees are a medically high-risk group.

Objectives: To compare pediatric department admission rates from the pediatric emergency department (PED) of refugees and Israelis.

Methods: We compared data from refugee and Israeli children admitted to the pediatric department at Wolfson Medical Center in Israel between 2013–2017.

Results: A total of 104,244 patients (aged 0–18 years) came to the PED. Admission rate to the pediatric department for refugees was 695/2541 (27%) compared to 11,858/101,703 (11.7%) Israeli patients (P < 0.001). Hospital stay for patients 0–2-years of age was 3.22 ± 4.80 days for refugees vs. 2.78 ± 3.17 for Israelis (P < 0.03). Re-admission rate within 7 days was 1.3% for refugees and 2.6% for Israelis (P < 0.05). Dermatological diseases (e.g., impetigo and cellulitis) were more frequent in refugees (23.30% vs. 13.15%, P < 0.01); however, acute gastroenteritis and respiratory diagnoses were more common in Israelis (18.52% vs. 11.72%, P < 0.05 and 14.84% vs. 6.26%, P < 0.01, respectively). Neurological diseases (e.g., febrile convulsions) were also more frequent in Israelis (7.7% vs. 3%, P < 0.05). Very significantly, 23% of refugees had no healthcare coverage, while only 0.2% of the Israelis had none (P < 0.001).

Conclusions: We found significant morbidity in refugees compared to the local Israeli pediatric population, highlighting the need for different approaches for each population.

Background: Intrathoracic cancer can cause hyponatremia, but it is uncertain whether mild hyponatremia in the outpatient setting should be regarded as an early sign of intrathoracic cancer.

Objectives: To evaluate the risk of undiagnosed intrathoracic cancer in patients with new persistent mild hyponatremia.

Methods: We conducted a retrospective cohort study using the electronic health record database of a large healthcare organization. The hyponatremia group included patients with sodium concentration of 130–134 mmol/L twice, after a previous normal value and without previous history of cancer or diseases related to hyponatremia. A control group with normal sodium concentration was matched by sex, age, and year of testing. We measured specific intrathoracic cancer incidence during 3 years of follow-up after sodium concentration test date. A logistic regression was used to adjust for further clinical information including smoking history, symptoms, and medications.

Results: The study comprised 1539 participants with mild hyponatremia and 7624 matched controls. New intrathoracic cancer diagnosis was more common in the hyponatremia group during a 3-year follow-up; 1.49% in the hyponatremia group and 0.39% in the control group, crude odds ratio (OR) 3.84, 95% confidence interval (95%CI) 2.22–6.63. After adjustment, hyponatremia remained a significant risk factor for the diagnosis of intrathoracic cancer; adjusted OR 3.61, 95%CI 2.08–6.28.

Conclusions: New mild persistent hyponatremia might be a significant predictive marker to a yet undiagnosed intrathoracic cancer.

Background: Several approaches are used to access the hip joint; most common are the direct lateral and posterior. Little consensus exists on which to use when treating hip fractures.

Objectives: To compare short-term complications, postoperative ambulation, and patient-reported outcome measures (PROMS) of direct lateral vs. posterior approaches in hemiarthroplasty for acute hip fractures.

Methods: We conducted a retrospective clinical trial with 260 patients who underwent bipolar hemiarthroplasty in the direct lateral or posterior approach (166 and 94, respectively) between January 2017 and December 2018. The clinical data included short-term complications: prosthetic dislocation, periprosthetic fractures, and infection. Postoperative ambulation was collected 6 weeks postoperatively; PROMS were collected for 173 patients at 2 years follow-up.

Results: There were six dislocations overall, average time to dislocation was 22 days postoperative (range 4–34). Five dislocations were after the posterior approach (5.3%) and one after direct lateral (0.6%) (P = 0.01). At 6 weeks follow-up, inability to walk was found in 16.9% of the direct lateral group and 6.4% of the posterior approach group (P = 0.02). In the posterior approach group, 76% could walk more than 20 meters; only half of the direct lateral group could (P = 0.0002). At 2 years follow-up, PROMS did not show a statistically significant difference between the groups.

Conclusions: Posterior approach for hemiarthroplasty following femoral neck fractures allows superior ambulation to the direct lateral approach only for the short-term. However, no long-term clinical advantage was found. This short-term benefit does not justify the increased dislocation rate in the posterior approach.

Background: Acute appendicitis (AA) is a medical emergency. The standard of care for AA had been surgical appendectomy. Recently, non-operative management (NOM) has been considered, mainly for uncomplicated AA.

Objectives: To evaluate AA NOM trends over two decades.

Methods: We conducted a retrospective cohort study based on Israel’s National Hospital Discharges Database (NHDD). Inclusion criteria were AA admissions from 1 January 2000 to 31 December 2019, with either primary discharged diagnosis of AA, or principal procedure of appendectomy. Predefined groups were children (5 ≤ 18 years) and adults (≥ 18 years). We compared the last decade (2010–2019) with the previous one (2000–2009).

Results: The overall AA incidence rate over two decades was 126/100,000/year; higher in children 164/100,000/year than 113/100,000/year in adults. Surgery was the predominant AA treatment in 91.9%; 93.7% in children and 91.1% in adults. There was an increase in AA NOM rates when comparing the previous decade (5.6%) to the past decade (10.2%); 3.2% vs. 9.1% in children and 6.8% vs. 10.7% in adults, respectively. Annual trends revealed a mild increase in AA NOM rates. Delayed appendectomy (within 90 days of AA NOM) was 19.7% overall; 17.3% in adults and 26.3% in children.

Conclusions: There was an increase in AA NOM rates during the last decade in the overall population. Since 2015, there has been a noticeable increase in AA NOM rates, probably associated with World Society of Emergency Surgery Jerusalem guidelines. Surgery is still the predominant treatment for AA despite the increasing trend in NOM.

Background: Previous epidemiological studies on shoulder instability evaluated specific and relatively small subgroups of patients.

Objectives: To determine the incidence rate of primary shoulder dislocations.

Methods: Cohort analysis of electronic health records from 2004 to 2019 was conducted in a urban district of a major health maintenance organization (HMO) in Israel. Patients presented with primary shoulder dislocation that was treated with closed reduction in any medical facility within the district. Overall incidence density rates (IDR) of primary shoulder dislocations and stabilization surgeries were determined.

Results: Over a period of 16 years 13,158 patients underwent closed reduction of primary shoulder dislocation. Of those, 712 shoulder stabilization surgeries were performed (5%). The IDR of primary shoulder dislocations were 124 per 100,000 person-years. The IDR of primary shoulder stabilizations were 7 per 100,000 person-years. The peak in the number of dislocations was observed in those 20–29 years old and ≥ 60 years of. In patients under 59 years old, dislocations were more common in men. In those ≥ 60 years of age, dislocations were more common in women. Most shoulder stabilization surgeries were performed on young patients. The annual mean time from the first dislocation to stabilization surgery linearly declined to 6 months in 2019.

Conclusions: The IDR of primary shoulder dislocations calculated from the largest HMO in Israel were 124 per 100,000 person-years. Shoulder dislocations had bimodal age distribution. Overall, 5% of the patients (mainly young) with shoulder dislocations underwent shoulder stabilization surgery during the study period.

Background: Clinical dysentery causes hundreds of thousands of deaths annually worldwide. However, current recommendations reserve antibiotics for those either clinically sick or with highly suspected cases of shigellosis. This treatment stems from rising antibiotic resistance. Children diagnosed with clinical dysentery in the pediatric emergency department (PED) are regarded more cautiously.

Objectives: To explore the use of antibiotics in children diagnosed with clinical dysentery in the PED.

Methods: A retrospective case study of children with clinical dysentery at a single PED during the years 2015 and 2018. Demographics as well as clinical findings were compared to culture results and antibiotic treatment.

Results: The study included 281 children who were diagnosed with clinical dysentery during the study period; 234 (83%) were treated with antibiotics. However, cultures were positive in only 162 cases (58%). Only 32% were Shigella spp. Younger age, fever, and leukocytosis were related to antibiotic treatment.

Conclusions: The diagnosis of clinical dysentery is misgiven commonly in the PED leading to widespread use of antibiotics when not indicated. This treatment may impact antibiotic resistance patterns. Further studies and interventions are necessary to create clear guidelines in the PED setting.

Background: Bacterial meningitis (BM) remains a considerable cause of morbidity.

Objectives: To evaluate BM incidence rate trends in diverse age groups.

Methods: We conducted a retrospective cohort study based on the Israeli national registry. Inclusion criteria were acute admissions 2000 to 2019 with primary diagnosis of BM. Predefined age groups were neonates (≤ 30 days), infants (31 days to 1 year), younger children (1 ≤ 5 years), older children (5 ≤ 18 years), and adults (≥ 18 years). Average annual incidence rates per 100,000/year were calculated for the entire period and by decade. Incidence rates for neonates and infants were calculated per 100,000 live births (LB).

Results: There were 3039 BM cases over 2 decades, 60% were adults. The overall BM incidence rate was 2.0/100,000/year, neonates, 5.4/100,000/year LB, infants 17.6/100,000/year LB. First year of life incidence rate (neonates and infants combined) was 23.0/100,000/year, younger children 1.5/100,000/year, older children 0.9/100,000/year, and adults 1.8/100,000/year. All age groups presented a decrease in incidence rate (last decade vs. previous) except neonates, which increased by 34%. Younger and older children presented the most considerable decrease: 48% and 37% (last decade vs. previous).

Conclusions: Adults showed the highest number of BM cases. The incidence rate was highest during the first year of life (neonates and infants combined). All age groups, except neonates, showed a decreasing trend. Younger and older children presented the most considerable decrease, most likely attributable to vaccination. The observed increase in BM incidence rate in neonates may influence whether preventive strategy is considered.

Background: The prognosis of long-term clinical outcomes for each patient is of utmost importance.

Objectives: To evaluate the association between rates of family attendance during rounds and long-term outcomes.

Methods: We conducted a historic cohort study.

Results: We followed 200 consecutive patients for a median of 19 months. Within the group of patients that had family members present in > 75% of rounds, the 30-day re-hospitalization rate was tenfold higher (P = 0.017). The overall prognosis (including median survival length) of patients who had the highest rates of family attendance (> 75%) was significantly worse compared to patients who had lower rates (P = 0.028). High rates of family attendance were found to correlate with other established risk factors for long-term mortality, including advanced age (r = 0.231, P = 0.001) and in-hospital delirium.

Conclusions: High family attendance during physician rounds in an internal medicine department is associated with worse patient prognosis.

Background: Blood pressure (BP) is routinely measured while triaging children presenting to the pediatric emergency department (PED).

Objectives: To determine whether a medical clown shortens the time to acquire a BP measurement among children undergoing triage in the PED.

Methods: The study comprised 133 children. Patients were assigned to one of two groups: with a medical clown or without a medical clown.

Results: The presence of a medical clown led to a significantly shorter time to acquire a blood pressure measurement (60 ± 23 seconds vs. 81 ± 43.5 seconds, P < 0.001. Clowns had a significant effect on shortening total triage length among children of Jewish ethnicity compared to Arab ethnicity (113 ± 353.6 seconds vs. 154 ± 418 seconds, P = 0.012).

Conclusions: Using medical clowns while measuring BP during triage when used in a culturally appropriate manner shortens time.