Israel Medical Association Journal

Background: One-third of patients with acute decompensated heart failure (ADHF) develop worsening kidney function, known as type I cardiorenal syndrome (CRS). CRS is linked to higher mortality rates, prolonged hospital stays, and increased readmissions.

Objectives: To explore the impact of real-time monitoring of urinary output (UO) trends on personalized pharmacologic management, fluid balance, and clinical outcomes of patients with ADHF admitted to a cardiac intensive care unit.

Methods: Our study comprised 35 patients who were hospitalized with ADHF and continuously monitored for UO (UO_elec). Standard diuretic and fluid protocols were implemented after 2 hours of oliguria, and patient outcomes were compared to a historical matched control (HMC) group. Patients were assessed for daily and cumulative fluid balance (over 72 hours) as well as for the occurrence of acute kidney injury (AKI).

Results: Significantly more patients in the UO_elec group demonstrated negative fluid balance daily and cumulatively over time in the intensive care unit compared to the HMC group: 91% vs. 20%, respectively (P < 0.0001 for 72-hour cumulative fluid balance). The incidence of AKI was significantly lower in the UO_elec monitoring cohort compared to the HMC: 23% vs. 57%, respectively (P = 0.003). Moreover, higher AKI resolution, and lower peak serum creatinine levels were demonstrated in the UO_elec group vs. the HMC group.

Conclusions: Implementing real-time monitoring of UO in ADHF patients allowed for early response to oliguria and goal-directed adjustment to treatment. This finding ultimately led to reduced congestion and contributed to early resolution of AKI.

Background: Cesarean deliveries (CD) are commonly performed using neuraxial anesthesia. The use of neuraxial morphine has proven beneficial in terms of postoperative pain management; however, its effect on postoperative urine retention remains unclear.

Objectives: To determine whether morphine injection into the neuraxis during CD influences postoperative urinary retention rate.

Methods: We conducted a retrospective case-control observational study of patients undergoing CD. We compared patients using morphine injected into the intrathecal or epidural spaces (November 2020 to October 2021) to a historical cohort of patients undergoing CD without morphine (November 2019 to October 2020). The primary outcome was the rate of postoperative overt urinary retention necessitating bladder catheterization.

Results: The study group comprised 283 patients, and 313 patients in the control group were eligible for analysis. No differences were found with respect to the baseline demographic and indication for CD. The number of postpartum urinary bladder catheterizations due to urine retention was higher in the study group (5% vs. 1%, P-value = 0.003). No cases of 30-day readmission were recorded. Moreover, patients treated with neuraxial morphine required fewer repeat doses of postoperative anesthesia (oral analgesia 7.4 vs. 10.1, intravenous analgesia 0.29 vs. 0.31, oral opioids 0.06 vs. 3.70, intravenous opioids 0.01 vs. 0.45, P-value < 0.001 for all)

Conclusions: While neuraxial morphine used during CD appears to be safe and effective, the risk of postoperative urinary retention seems to be increased due to its use. Cases of overt urinary retention treated by bladder catheterization does not lead to short-term complications.

Background: Pediatric urolithiasis is relatively uncommon and is generally associated with predisposing anatomic or metabolic abnormalities. In the adult population, emergency department (ED) admissions have been associated with an increase in ambient temperature. The same association has not been evaluated in the pediatric population.

Objectives: To analyze trends in ED admissions due to renal colic in a pediatric population (≤ 18 years old) and to assess the possible effect of climate on ED admissions.

Methods: We conducted a retrospective, multicenter cohort study, based on a computerized database of all ED visits due to renal colic in pediatric patients. The study cohort presented with urolithiasis on imaging during their ED admission. Exact climate data was acquired through the Israeli Meteorological Service (IMS).

Results: Between January 2010 and December 2020, 609 patients, ≤ 18 years, were admitted to EDs in five medical centers with renal colic: 318 males (52%), 291 females (48%). The median age was 17 years (IQR 9–16). ED visits oscillated through the years, peaking in 2012 and 2018. A 6% downward trend in ED admissions was noted between 2010 and 2020. The number of ED admissions in the different seasons was 179 in autumn (30%), 134 in winter (22%), 152 in spring (25%), and 144 in summer (23%) (P = 0.8). Logistic regression multivariable analysis associated with ED visits did not find any correlation between climate parameters and ED admissions due to renal colic in the pediatric population.

Conclusions: ED admissions oscillated during the period investigated and had a downward trend. Unlike in the adult population, rates of renal colic ED admissions in the pediatric population were not affected by seasonal changes or rise in maximum ambient temperature.

Background: Cardiac amyloidosis (CA) is characterized by the extracellular deposition of misfolded protein in the heart. Precise identification of the amyloid type is often challenging, but critical, since the treatment and prognosis depend on the disease form and the type of deposited amyloid. Coexistence of clinical conditions such as old age, monoclonal gammopathy, chronic inflammation, or peripheral neuropathy in a patient with cardiomyopathy creates a differential diagnosis between the major types of CA: amyloidosis light chains (AL), amyloidosis transthyretin (ATTR) and amyloidosis A (AA).

Objectives: To demonstrate the utility of the Western blotting (WB)-based amyloid typing method in patients diagnosed with cardiac amyloidosis where the type of amyloid was not obvious based on the clinical context.

Methods: Congo red positive endomyocardial biopsy specimens were studied in patients where the type of amyloid was uncertain. Amyloid proteins were extracted and identified by WB. Mass spectrometry (MS) of the electrophoretically resolved protein-in-gel bands was used for confirmation of WB data.

Results: WB analysis allowed differentiation between AL, AA, and ATTR in cardiac biopsies based on specific immunoreactivity of the electrophoretically separated proteins and their characteristic molecular weight. The obtained results were confirmed by MS.

Conclusions: WB-based amyloid typing method is cheaper and more readily available than the complex and expensive gold standard techniques such as MS analysis or immunoelectron microscopy. Notably, it is more sensitive and specific than the commonly used immunohistochemical techniques and may provide an accessible diagnostic service to patients with amyloidosis in Israel.

Background: Fetal facial clefts are among the most common congenital anomalies detected prenatally. This finding may lead to termination of pregnancy in some cases.

Objectives: To compare a cohort of fetuses with facial clefts in which the pregnancy was terminated to the cohort of cases that were born with facial clefts. To investigate risk factors for facial clefts.

Methods: We conducted a retrospective chart review of all women with prenatal and postnatal diagnosis of facial cleft that were managed in our institute. A telephone questionnaire was conducted regarding a positive family history and/or genetic predisposition for facial clefts abnormalities.

Results: The final cohort consisted of two group. One group included 54 cases of termination of pregnancy (TOP) that were performed due to cleft lip (CL) or cleft palate (CLP); 27 women answered the telephone questionnaire. The second group comprised 99 women who delivered children with facial cleft during the same period; 60 answered the questionnaire. Only seven cases were diagnosed prenatal. Among the two groups, no correlation to family history was discovered. Of note, there was one case of three consecutive fetuses with CL in one woman, without any significant genetic findings.

Conclusions: To the best of our knowledge, this is the first study to describe an anatomical malformation posing an ethical dilemma before TOP. Primary prevention with folic acid and early sonographic detection of CL/CLP with multidisciplinary consultation should be considered.

Background: Up to half the patients diagnosed with acute coronavirus disease 2019 (COVID-19) presented with gastrointestinal symptoms. Gastric mucosal cells, enterocytes, and colonocytes express the viral entry receptor angiotensin-converting enzyme 2 (ACE2) and coreceptor transmembrane protease serine 2 (TMPRSS2) and are prone to infection. Direct infection of gastrointestinal epithelial cells has been demonstrated. COVID-19 disease was first diagnosed in Israel at the end of February 2020 with 842,536 confirmed cases and 6428 deaths by the end of June 2021. In our multicenter, retrospective cohort study, we looked for gastrointestinal signs and symptoms in two periods and correlated them with mortality. Period 1 included the first and second waves and the original virus. Period 2 represented the third wave and the alpha variant.

Objectives: To reveal gastrointestinal signs and symptoms in two periods and correlate them with mortality.

Methods: From 22,302 patients hospitalized in general medical centers, we randomly selected 3582 from Period 1 and 1106 from Period 2. The study was performed before vaccinations were available.

Results: Gastrointestinal signs and symptoms, diarrhea, vomiting, abdominal pain, and taste/smell loss were significantly more prevalent during Period 1. Thirty-day mortality and in-hospital mortality were significantly higher in Period 2 than in Period 1, 25.20% vs. 13.68%, and 21.17% vs. 12.87%, respectively (P < 0.001).

Conclusions: Thirty-day mortality and in-hospital mortality rates were 1.84 and 1.64 times higher from 6 November 2020 to 15 January 2021, the alpha variant, and in negative correlation with gastrointestinal symptoms.

Background: Morbidly adherent placentation (MAP) increases the risk for obstetric hemorrhage. Cesarean hysterectomy is the prevalent perioperative approach. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a minimally invasive and relatively simple endovascular procedure to temporarily occlude the aorta and control below diaphragm bleeding in trauma. It has been effectively used to reduce obstetric hemorrhage.

Objectives: To evaluate whether REBOA during cesarean delivery (CD) in women with morbidly adherent placentation is a safe and effective treatment modality.

Methods: We introduced REBOA for CD with antepartum diagnosis of MAP in 2019 and compared these patients (RG) to a standard approach group (SAG) treated in our center over the preceding year, as a control. All relevant data were collected from patient electronic files.

Results: Estimated blood loss and transfusion rates were significantly higher in SAG; 54.5% of SAG patients received four RBC units or more vs. one administered in RG. No fresh frozen plasma, cryoprecipitate, or platelets were administered in RG vs. mean 3.63, 6, and 3.62 units, respectively in SAG. Ten SAG patients (90.9%) underwent hysterectomy vs. 3 RG patients (30%). Five SAG patients (45%) required post-surgical intensive care unit (ICU) admission vs. no RG patients. Bladder injury occurred in five SAG cases (45%) vs. 2 RG (20%). One RG patient had a thromboembolic event. Perioperative lactate levels were significantly higher in SAG patients.

Conclusions: Use of REBOA during CD in women with MAP is safe and effective in preventing massive bleeding, reducing the rate of hysterectomy, and improving patient outcome.

Background: Perianal abscesses require immediate incision and drainage (I&D). However, prompt bedside drainage is controversial as it may compromise exposure and thorough anal examination.

Objectives: To examine outcomes of bedside I&D of perianal abscesses in the emergency department (ED) vs. the operating room (OR).

Methods: We conducted a retrospective review of all patients presented to the ED with a perianal abscesses between January 2018 and March 2020. Patients with Crohn’s disease, horseshoe or recurrent abscesses were excluded.

Results: The study comprised 248 patients; 151 (60.89%) underwent I&D in the OR and 97 (39.11%) in the ED. Patients elected to bedside I&D had smaller abscess sizes (P = 0.01), presented with no fever, and had lower rates of inflammatory markers. The interval time from diagnosis to intervention was significantly shorter among the bedside I&D group 2.13 ± 2.34 hours vs. 10.41 ± 8.48 hours (P < 0.001). Of patients who underwent I&D in the OR, 7.3% had synchronous fistulas, whereas none at bedside had (P = 0.007). At median follow-up of 24 months, recurrence rate of abscess and fistula formation in patients treated in the ED were 11.3% and 6.2%, respectively, vs. 19.9% and 15.23% (P = 0.023, 0.006). Fever (OR 5.71, P = 0.005) and abscess size (OR 1.7, P = 0.026) at initial presentation were risk factors for late fistula formation.

Conclusions: Bedside I&D significantly shortens waiting time and does not increase the rates of long-term complications in patients with small primary perianal abscesses.

Background: The neutrophil to lymphocyte ratio (NLR) has demonstrated prognostic value in various malignant conditions, including gastric adenocarcinoma. However, chemotherapy may affect NLR.

Objectives: To evaluate the prognostic value of NLR as an accessory decision-making tool in terms of operating patients after neoadjuvant chemotherapy in patients with resectable gastric cancer.

Methods: We collected oncologic, perioperative, and survival data of patients with gastric adenocarcinoma who underwent curative intent gastrectomy and D2 lymphadenectomy between 2009 and 2016. The NLR was calculated from preoperative laboratory tests and classified as high (> 4) and low (≤ 4). The t-test, chi-square, Kaplan-Meier analysis, and Cox multivariate regression models were used to assess associations of clinical, histologic, and hematological variables with survival.

Results: For 124 patients the median follow-up was 23 months (range 1–88). High NLR was associated with greater rate of local complication (r=0.268, P < 0.01). The rate of major complications (Clavien-Dindo ≥ 3) was higher in the high NLR group (28% vs. 9%, P = 0.022). Among the 53 patients who received neoadjuvant chemotherapy, those with low NLR had significantly improved disease-free survival (DFS) (49.7 vs. 27.7 months, P = 0.025). Low NLR was not significantly associated with overall survival (mean survival, 51.2 vs. 42.3 months, P = 0.19). Multivariate regression identified NLR group (P = 0.013), male gender (P = 0.04), and body mass index (P = 0.026) as independently associated with DFS.

Conclusions: Among gastric cancer patients planned for curative intent surgery who underwent neoadjuvant chemotherapy, NLR may have prognostic value, particularly regarding DFS and postoperative complications.

Background: During coronavirus disease 2019 (COVID-19) pandemic, less isolation of common winter viruses was reported in the southern hemisphere.

Objectives: To evaluate annual trends in respiratory disease-related admissions in a large Israeli hospital during and before the pandemic.

Methods: A retrospective analysis of medical records from November 2020 to January 2021 (winter season) was conducted and compared to the same period in two previous years. Data included number of admissions, epidemiological and clinical presentation, and isolation of respiratory pathogens.

Results: There were 1488 respiratory hospitalizations (58% males): 632 in 2018–2019, 701 in 2019–2020, and 155 in 2020–2021. Daily admissions decreased significantly from a median value of 6 (interquartile range [IQR] 4–9) and 7 per day (IQR 6–10) for 2018–2019 and 2019–2020, respectively, to only 1 per day (IQR 1–3) in 2020–2021 (P-value < 0.001). The incidence of all respiratory viruses decreased significantly during the COVID-19 pandemic, with no hospitalizations due to influenza and only one with respiratory syncytial virus. There was also a significant decline in respiratory viral and bacterial co-infections during the pandemic (P-value < 0.001).

Conclusions: There was a significant decline in pediatric respiratory admission rates during the COVID-19 pandemic. Possible etiologies include epidemiological factors such as mask wearing and social distancing, in addition to biological factors such as viral interference. A herd protection effect of adults and older children wearing masks may also have had an impact.

Background: Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver disorders. Acute cholangitis (AC) is a life-threatening illness.

Objective: To determine whether NAFLD is a risk factor for the severity of AC.

Methods: We retrospectively studied hospitalized patients with a diagnosis of AC over 5 years. Patients were divided into a NAFLD group and a non-NAFLD group. We compared the two groups with regard to demographic characteristics, co-morbidities, laboratory data, and severity of AC (including Charlson Comorbidity Index [CCI] and Tokyo Consensus meeting criteria).

Results: In all, 298 of 419 hospitalized patients diagnosed with AC met the inclusion criteria. Of these, 73/298 (24.5%) were in the NAFLD group. NAFLD group patients were younger and more likely to be diabetic and obese than the non-NAFLD group. Participants in the NAFLD presented with higher serum C-reactive protein and higher liver enzymes (P < 0.05, for each parameter) and with more events of organ dysfunction (P < 0.001) and bacteremia (P < 0.005). Regarding the severity of AC according to Tokyo Consensus, among the NAFLD group more patients presented with Grade II (39.7 vs. 33.3%, P < 0.001) and Grade III (23.3 vs. 18.3, P < 0.001) cholangitis. More Grade I cholangitis was found among the non-NAFLD group (48.4 vs. 37%, P < 0.001). Multivariate logistic regression analysis showed that NAFLD was independently associated with severe AC, Grade III (odds ratio 3.25, 95% confidence interval 1.65–6.45, P = 0.038).

Conclusions: NAFLD is an independent risk factor for the severity of AC.

Background: Acquired hepatocerebral degeneration (AHD) is a neurologic complication of severe chronic liver disease (CLD) with portosystemic shunts. The proposed etiology is manganese accumulation in the brain tissue, especially in the basal ganglia. Combination of clinical manifestation, mostly extrapyramidal movement disorders, and hyperintensities on T1-weighted brain magnetic resonance imaging (MRI) is diagnostic. Although liver transplantation controversial, it is suggested for AHD.

Objectives: To depict clinical and neuroimaging characteristics and response to treatments in patients diagnosed with AHD at Sheba Medical Center.

Methods: Review of patients with AHD diagnosis at the Liver Diseases Center at Sheba Medical Center between 2012 and 2017, data of clinical and neuroimaging, follow-up, and response to treatments, including liver transplantation were recorded.

Results: Five patients with diagnosis of AHD were identified, median age at diagnosis 55 years (range 45–64 years). Four patients had cirrhosis at the time of AHD diagnosis. The main risk factor for AHD was the presence of portosystemic shunts. The most prevalent clinical manifestations were movement disorders, specifically a combination of extrapyramidal and cerebellar signs including instability, rigidity, tremor, bradykinesia, and cognitive impairment. Brain MRI revealed hyperintensities on T1-weighted images in the basal ganglia in all patients. Administration of antiparkinsonian drugs showed clinical improvement, whereas liver transplantation performed in two patients was not associated to neurological improvement.

Conclusions: AHD is related to portosystemic shunts. The combination of Parkinsonism and cerebellar signs and MRI pallidal lesions should alert physicians to the diagnosis. The role of liver transplantation in AHD is still controversial.

Background: School closures due to the coronavirus disease 2019 (COVID-19) outbreak affected students physically, socially, and psychologically with an increase in the number of children and adolescent presenting with anxiety, depression, and drug abuse.

Objectives: To examine the impact of COVID-19 and lockdown on the mental health of minors during the pandemic period and to characterize the type and number of referrals to a regional psychiatric outpatient clinic.

Methods: This study included 380 children evaluated in an outpatient child psychiatric clinic. They were divided into two groups: before the lockdowns (BLD) (n=248), from January 2019 to February 2020, and during the lockdowns (LD) (n=132), from March 2020 to April 2021.

Results: When comparing the LD to BLD, there was increase in suicide attempts (9.8% vs. 2.8%) and in the use of psychotherapy (81% vs. 56%). There was a decrease in the diagnoses of behavior disorders (29.5% vs. 44.8%) and ADHD (29.5% vs. 50%); as well as a decrease in stimulant usage (22.7% vs. 38%). There was a statistically non-significant increase in the number of children with depression, anxiety, and drug-use disorder.

Conclusions: Many children developed educational, social, emotional, and behavioral gaps during LD, and they lost skills to deal with everyday problems due to social isolation. It is important to follow the long-term impact of the lockdowns and social isolation.

Background: National registries for acromegaly and population-based data make an important contribution to disease understanding and management. Data concerning the epidemiology of acromegaly in Israel is scanty.

Objectives: To evaluate the epidemiology of acromegaly in different industrial areas in northern Israel.

Methods: Data from adult patients diagnosed with acromegaly from 2000 to 2020, living in Haifa and the western Galilee District were collected using the electronic database and medical records from Clalit Health Services. The prevalence of acromegaly in three distinct areas and overall were reported. In addition, other epidemiological data including associated co-morbidities, pituitary tumor size, and treatment modalities were collected.

Results: We identified 77 patients with a confirmed diagnosis of acromegaly. The overall prevalence was 155 cases/10⁶ inhabitants without statistically significant differences between the three areas. The mean age at diagnosis was 50 ± 1.8 years and the male to female ratio was 1.1. Macroadenoma and microadenoma were identified in 44 (57%) and 25 (33%), respectively. The frequency rate of acromegaly-associated co-morbidities such as diabetes, hypertension, carpal tunnel syndrome, and osteoporosis was similar to previously reported studies. The mean body mass index (BMI) was 29 ± 5.6 kg/m² .Obesity, with a BMI ≥ of 30 kg/m², was found in 29 patients (38%). The majority of patients underwent transsphenoidal surgery 67 (87%). Normalized insulin-like growth factor 1 was reported in 64 (83%).

Conclusions: A high prevalence of acromegaly was found in northern Israel. The pituitary microadenoma frequency rate is the highest reported.

Background: Low back pain has been the leading cause for disability worldwide for several decades, and clinical guidelines for its management clearly emphasize a multifactorial approach. Yet, current guidelines are still not well implemented by clinicians.

Objectives: To explore the attitudes of family medicine residents regarding low back pain and to determine whether they positively correlate with their treatment approaches. To test if these attitudes can be affected by the Enhanced Transtheoretical Model Intervention (ETMI), a guideline-based workshop.

Methods: Participants completed an online questionnaire regarding their attitudes toward low back pain and clinical habits, after which they attended an online ETMI educational workshop. One month later all participants were asked to complete the questionnaire a second time. Statistical analysis was conducted to explore the attitudes of the residents and clinical approaches, as well as any associations between them, as well as possible differences pre- and post-intervention.

Results: The participants exhibited highly psychologically oriented attitudes. Correlations between the attitudes and treatment did not show consistent coherency. Results regarding the participants clinical approaches were revealed to have two distinct and opposed inclinations: biomedically and biopsychosocially. Last, results for the re-activation subscale were significantly higher post-intervention.

Conclusions: Family medicine residents seem to be highly psychologically oriented regarding low back pain; however, they do not necessarily treat their patients accordingly. Their clinical choices seem to follow two different approaches: guideline-consistent and non-guideline-consistent. An ETMI guideline-based workshop may sway their attitudes toward re-activation of patients. Further research is needed to determine whether similar results would arise in larger physician populations.