Israel Medical Association Journal

Background: Ptyalism gravidarum (PG) is a condition of hypersalivation that affects pregnant women early in gestation. Symptoms include massive saliva volumes (up to 2 liters per day), swollen salivary glands, sleep deprivation, significant emotional distress, and social difficulties.

Objectives: To examine maternal and fetal characteristics and pregnancy outcomes of patients with PG.

Methods: Patients diagnosed with PG in our clinic during the years 2001–2016 were identified and contacted. Demographic data were extracted from patient charts and clinical and outcome data was collected via telephone interviews.

Results: The incidence of PG was 1/963 (0.09%) in our sample. Eleven out of 22 women (40%) with PG were also diagnosed with hyperemesis gravidarum. Fetal gender did not increase the risk. Of the mothers presenting with PG, 37% had a positive family history for this condition. There was no associated increase in the rate of fetal or maternal complications. Two women reported a resolution of the symptoms immediately following hypnosis with acupuncture treatment.

Conclusions: Although PG represents an unpleasant mental and physical condition, it does not pose any specific risk to the health of the mother or increase adverse perinatal outcomes for the fetus. Alternative medicine could play a role in the treatment of PG.

Background: Door-to-balloon time (DTBT) ≤ 90 minutes has become an important quality indicator in the management of ST-elevation myocardial infarction (STEMI). We identified three specific problems in the course from arrival of STEMI patients at our emergency department to initiation of balloon inflation and determined an intervention comprised of specific administrative and professional steps. The focus of the intervention was on triage within the emergency department (ED) and on increasing the efficiency and accuracy of electrocardiography interpretation.

Objectives: To examine whether our intervention reduced the proportion of patients with DTBT > 90 minutes.

Methods: We compared DTBT of patients admitted to the ED with STEMI during the year preceding and the year following implementation of the intervention.

Results: Demographic and clinical characteristics at presentation to the ED were similar for patients admitted to the ED in the year preceding and the year following intervention. The year preceding intervention, DTBT was > 90 minutes for 19/78 patients (24%). The year after intervention, DTBT was > 90 minutes for 17/102 patients (17%). For both years, the median DTBT was 1 hour. Patients with DTBT > 90 minutes tended to be older and more often female. Diagnoses in the ED were similar between those with DTBT ≤ 90 minutes and > 90 minutes. In-hospital mortality was 17% (13/78) and 14% (14/102) for the respective time periods.

Conclusions: An intervention specifically designed to address problems identified at one medical center was shown to decrease the proportion of patients with DTBT > 90 minutes.

Background: Evidence has been emerging that Helicobacter pylori may also impact colorectal cancer (CRC). Positron emission tomography/computed tomography (PET/CT) imaging can predict overall survival in CRC patients.

Objectives: To determine a possible association between H. pylori seropositivity and all-cause mortality among CRC patients evaluated by PET/CT scans.

Methods: This prospective cohort study was comprised of 110 consecutive CRC patients who had undergone a PET/CT evaluation in a tertiary academic medical center. Data included demographics, body mass index (BMI), tumor node metastasis stage at diagnosis, treatment, time from diagnosis to PET/CT, and PET/CT findings. All patients were tested for anti-H. pylori immunoglobulin G (IgG) antibodies and followed for 36 months from the day of the PET/CT scan. Mortality was documented. Univariate and multivariate Cox regression was used to estimate the hazard ratio (HR) of H. pylori serological status.

Results: During the follow-up period, of the 110 CRC patients 41 (37.3%) died and 69 (62.7%) survived. Of the 41 patients, 26 (63.4%) were H. pylori seropositive and 15 (36.6%) were seronegative. Multivariate analysis showed that H. pylori seropositivity was associated with increased mortality (HR 3.46, 95% confidence interval 1.63–7.32), stage IV at diagnosis, metastatic disease found on PET/CT, longer time from diagnosis to PET/CT, lower BMI, and older age.

Conclusions: Our findings suggest that H. pylori infection may be a risk factor for all-cause mortality among CRC patients who are evaluated by PET/CT. Multicenter studies with larger patient groups are needed to confirm our findings.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) (such as canagliflozin, empagliflozin, and dapagliflozin) are widely used to treat patients with type 2 diabetes mellitus (T2DM) to improve glycemic, cardiovascular and renal outcomes. However, based on post-marketing data, a warning label was added regarding possible occurrence of acute kidney injury (AKI).

Objectives: To describe the clinical presentation of T2DM patients treated with SGLT2i who were evaluated for AKI at our institution and to discuss the potential pathophysiologic mechanisms.

Methods: A retrospective study of a computerized database was conducted of patients with T2DM who were hospitalized or evaluated for AKI while receiving SGLT2i, including descriptions of clinical and laboratory characteristics, at our institution.

Results: We identified seven patients in whom AKI occurred 7–365 days after initiation of SGLT2i. In all cases, renin-angiotensin-aldosterone system blockers had also been prescribed. In five patients, another concomitant nephrotoxic agent (injection of contrast-product, use of nonsteroidal anti-inflammatory drugs or cox-2 inhibitors) or occurrence of an acute medical event potentially associated with AKI (diarrhea, sepsis) was identified. In two patients, only the initiation of SGLT2i was evident. The mechanisms by which AKI occurs under SGLT2i are discussed with regard to the associated potential triggers: altered trans-glomerular filtration or, alternatively, kidney medullary hypoxia.

Conclusions: SGLT2i are usually safe and provide multiple benefits for patients with T2DM. However, during particular medical circumstances, and in association with usual co-medications, particularly if baseline glomerular filtration rate is decreased, patients treated with SGLT2i may be at risk of AKI, thus warranting caution when prescribed.

Background: Shortened telomeres were found in patients with cirrhosis, probably reflecting chronic liver injury, continuous regeneration, and destruction of hepatic nodules.

Objectives: To test whether telomere shortening is a general marker of cirrhosis, independent of disease etiology.

Methods: We evaluated telomere length in patients with cryptogenic cirrhosis (largely a late sequela of steatohepatitis) compared to patients with cirrhosis caused by chronic hepatitis B and C (HBV/HCV). We also evaluated telomere aggregates, a sensitive parameter of telomere dysfunction and genetic instability. We analyzed peripheral lymphocytes from 25 patients with cryptogenic cirrhosis, 15 patients with cirrhosis due to chronic viral hepatitis, and 20 age-matched controls. Telomere length was analyzed using quantitative fluorescence in situ hybridization. Aggregate size was divided into three fusion groups of 2–5, 6–10, and 11–15 telomeres, relative to the size of a single telomere.

Results: Shorter telomere length was found in patients with cirrhosis from all three etiologies (mean 121.3 ± 24.1) compared to controls (mean 63.5 ± 23.5). In contrast, there was significantly more fusion of > 5 telomeres only in the HBV/HCV cirrhosis group compared to healthy controls (P = 0.023), but not in the cryptogenic cirrhosis group.

Conclusions: While shortened telomeres in peripheral lymphocytes are a general marker of liver cirrhosis, telomere aggregates may signify a more sensitive genetic instability parameter for the diverse, etiology-based malignant potential of cirrhosis. This finding is in agreement with the well-known higher tendency toward developing hepatocellular carcinoma with cirrhosis caused by chronic hepatitis relative to steatohepatitis.

Background: Right hydronephrosis secondary to acute appendicitis is an under-reported phenomenon with only several case reports published.

Objectives: To assess the incidence of this phenomenon in our database of patients diagnosed with acute appendicitis.

Methods: Data were collected on 1092 patients who underwent surgery due to acute appendicitis between 2003 and 2007 in our tertiary medical center. The data entailed demographic, surgical, and hospitalization parameters including ultrasound or computed tomography examinations and presence of right hydronephrosis prior to surgery.

Results: Out of 1092 patients, appendicitis was eventually diagnosed in 87.4% of the patients. Only 594 (54%) had preoperative imaging performed prior to surgery (ultrasound or computed tomography). Out of these 594 patients, 21 (3.5%) had a new right hydronephrosis diagnosed and all had appendicitis with 15/21 (71%) having a retrocecal appendix. Of those with retrocecal appendix, 10 were pregnant women (48%). Erythrocyturia was present in 15/21 patients (71%) and in 10/11 of patients (91%) after excluding those who were pregnant. No significant differences were seen in patients with hydronephrosis regarding age, hospitalization, and surgery time. In all patients, an ultrasound was performed 2 weeks after surgery demonstrating the disappearance of hydronephrosis. Median follow-up time was 41.7 months (range 14.8–118.4 months).

Conclusions: Our study shows that 3.5% of our cohort had right hydronephrosis secondary to acute appendicitis. Although this presentation is very rare, physicians should be aware of this phenomenon and the risk for delayed diagnosis and treatment of acute appendicitis.

Background: Since the introduction of the electrocardiogram (ECG) in 1902, the fundamentals of ECG data acquisition, display, and interpretation in the clinical arena have not changed much.

Objectives: To present a new method to enhance and improve acquisition, analysis, and display of the standard ECG.

Methods: We performed ECG enhancement by superimposition and summation of multiple standard ECG cycles of each lead, by temporal alignment to peak R wave and voltage alignment to an improved baseline, at the T-P segment.

Results: We enhanced ECG recordings of 504 patients who underwent coronary angiograms for routine indications. Several new ECG features were noted on the enhanced recordings. Examination of a subgroup of 152 patients with a normal rest 12-lead ECG led to the discovery of a new observation, which may help to distinguish between patients with and without coronary artery disease (CAD): namely, a spontaneous cycle-to-cycle voltage spread (VS) at the S-T interval, normalized to VS at the T-P interval. The mean normalized VS was significantly greater in those with CAD (n=61, 40%) than without (n=91, 60%), 5.61 ± 3.79 vs. 4.01 ± 2.1 (P < 0.05).

Conclusions: Our novel method of multiple ECG-cycle superimposition enhances the ECG display and improves detection of subtle electrical abnormalities, thus facilitating the standard rest ECG diagnostic power. We describe, for the first time, voltage spread at the S-T interval, an observed phenomenon that can help detect CAD among individuals with normal rest 12-lead ECG.

Background: Empiric treatment for Helicobacter pylori is influenced by antibiotic susceptibility of infecting strains. A rise in the resistance rate to clarithromycin and metronidazole has been reported in pediatric populations.

Objectives: To assess the primary and secondary antibiotic resistance of H. pylori isolates in Israeli children and adolescents.

Methods: A retrospective review of H. pylori isolates cultured from antral biopsies of consecutive children aged 1 to 18 years, who were referred to the Pediatric Gastroenterology Unit, Kaplan Medical Center, over a 2.8 year period, was performed. Antibiotic susceptibility to clarithromycin, metronidazole, amoxicillin, tetracycline, and levofloxacin was determined by E-test. Data on the age of the patient, indication for endoscopy, and antibiotic treatment for H. pylori in previously treated children was collected.

Results: Cultures for H. pylori yielded 123 isolates. In children not previously treated (n=95), the primary global resistance was 38% with resistance to clarithromycin 9.5%, metronidazole 32.6 %, and to both 4.2%. Respective rates of resistance in previously treated children (n=28) were 71% (P = 0.002), 29% (P = 0.02), and 61% (P = 0.007). Simultaneous resistance to both drugs was found in 18% (P = 0.02). All H. pylori strains were susceptible to amoxicillin, tetracycline, and levofloxacin. Past eradication treatment was the only independent risk factor for antibiotic resistance in multivariate analysis.

Conclusions: Significantly higher resistance rates were found in previously treated patients, stressing the need to refrain from empiric treatment using the "test and treat strategy." Culture-based treatment strategy should be considered in all previously treated children.

Background: Magnetic resonance imaging (MRI) is the most sensitive imaging modality for the detection of sacroiliitis. Diagnosing sacroiliitis on MRI is not always straightforward and can be challenging in some cases.

Objectives: To evaluate the prevalence of alternative diagnoses suggested by MRI and characterize the MR appearance of the most common ones.

Methods: Consecutive MRI examinations of the sacroiliac joints (SIJ) performed between 2005 and 2012 were retrospectively evaluated for the presence of structural and active sacroiliitis findings according to the Assessment of SpondyloArthritis International Society guidelines. Alternative diagnoses, including degenerative changes, diffuse idiopathic skeletal hyperostosis (DISH), Osteitis condensans ilii (OCI), septic sacroiliitis/discitis, stress reaction as well as anatomic variants, were registered

Results: We evaluated 281 MRI examinations, 116 males, 165 females, average age 44 ± 15 years. Sacroiliitis was found in 71 examinations (25%) and alternative diagnoses were suggested in 87 (31%) (OCI 8.9%, anatomic variants 5.3%, septic sacroiliitis 5.3%, degenerative findings 4.3%, diffuse idiopathic skeletal hyperostosis [DISH] 1.5%, stress reaction 0.7%, tumor 0.3%). A normal examination was found in the remaining 123 examinations. Patients with alternative diagnoses were older than those with sacroiliitis (62 vs. 47 years of age, respectively, P > 0.05). Alternative pathologies in the SIJ were significantly more common in females (66) than males (21), P < 0.05.

Conclusions: A substantial proportion of patients with suspected sacroiliitis had normal SIJ while the rest were more commonly diagnosed with other pathologies. A referral by an experienced rheumatologist may improve the sensitivity and specificity of this important examination.

Background: Enthesopathy may lead to calcification of the stylohyoid ligament and can cause elongation of the styloid process (SP).

Objectives: To evaluate whether SP elongation is associated with two common enthesitis-related diseases: ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH).

Methods: Cervical spine computed tomography (CT) examinations of patients with DISH (n=64, Resnick criteria), AS (n=24, New York criteria) and a controls (no radiological signs of DISH or AS, n=54) were retrospectively evaluated. The DISH group was further divided into patients with and without cervical DISH. The length of right and left SP was measured independently by two readers on coronal and sagittal curved reformats. The average right and left styloid length and average length per person were compared among the groups.

Results: Demographic characteristics were similar between the DISH and control groups (average age 68.2 ± 15.7, 69.2 ± 12.7 years, male:female ratio 48:16 and 35:19, respectively, P > 0.05), whereas age was significantly lower (average age: 53 ± 15 years, P < 0.0001) in the AS group, which was also composed mainly of men. The AS and DISH groups had significantly longer SP compared to controls (AS 37.9 ± 9.6 mm, DISH 34.4 ± 9 mm, control 30.3 ± 10.1 mm, P < 0.05). There was no correlation between age and SP length. Inter-reader reliability of SP measurements was excellent in all groups (ICC = 0.998, P < 0.0001).

Conclusions: SP elongation is associated with both AS and DISH substantiating the enthesopathy-related pathophysiology of this finding.

Background: Metal-on-metal total hip prostheses (MoM-THR) have been shown to produce hypersensitivity reactions and fluid collection (pseudotumor) by the hip as well as high blood metal ions levels (BMILs).

Objectives: To evaluate the magnetic resonance imaging (MRI) signal-to-noise ratio (S/N) in selected body tissues around the hip of patients who underwent MoM hip replacement and to correlate to BMILs.

Methods: Sixty-one MRI hip examinations in 54 post-MoM-THR patients (18 males, 36 females, mean age 65 years) were retrospectively evaluated independently by two readers. The mean S/N ratio in a region of interest was calculated for periprosthetic pseudotumor collection (PPC), the bladder, fat, and muscle on axial T1w, FSE-T2w, and short tau inversion recovery (STIR) sequences on the same location. BMILs were retrieved from patient files.

Results: PPC was detected in 32 patients (52%) with an average volume of 82.48 mm³. BMIL did not correlate with the presence of PPCs but positively correlated with the PPC's volume. A trend for positive correlation was found between BMILs and S/N levels of STIR images for muscle and bladder as well as for PPC and cobalt levels. A trend for correlation was also seen between BMIL with PPC's T1 w S/N.

Conclusions: Alteration of MRI S/N for different hip tissues showed a tendency for correlation with BMILs, possibly suggesting that metal deposition occurs in the PPC as well as in the surrounding tissues and bladder.

Background: Facial rejuvenation using different dermal and sub-dermal injectable compounds is a popular cosmetic procedure which may pose a diagnostic dilemma to the radiologist.

Objectives: To describe the appearance of cosmetic facial fillers on PET-CT.

Methods: All PET-CT exams performed between January 2015 and May 2017 in which findings suggestive of prior facial filler procedures was evident and where anamnestic confirmation with the patient was possible were reviewed.

Results: We describe five females who had undergone facial filler procedures leading to calcifications around the mouth and nasolabial triangle.

Conclusions: Familiarity with the appearance of such cosmetic procedures on PET-CT is of paramount importance in order to avoid misinterpretation of the findings leading to unnecessary apprehension and work-up.