Israel Medical Association Journal

Background: Esophageal cancer is comprised of adenocarcinoma and squamous cell carcinoma and is the sixth leading cause of cancer-related mortality worldwide. Upper endoscopy may reveal a partially or completely lumen-occluding mass at diagnosis, yet the prognostic significance of such a presentation is not clear.

Objectives: To investigate whether endoscopic obstructing lesions have a meaning regarding patient prognosis.

Methods: We reviewed upper gastrointestinal endoscopic studies performed over a 20-year period (2000–2020). We compared overall survival, disease stage, histologic criteria, and anatomic location of the lesions in esophagus lumen-obstructing and non-obstructing tumors. Differences between the two groups were statistically evaluated.

Results: Sixty-nine patients were diagnosed with histologically confirmed esophageal cancer. As assessed through endoscopy, 32/69 (46%) patients had obstructive and 37/69 (54%) had non-obstructive cancers. Median survival was significantly shorter in the lumen-obstructing lesions compared with the non-obstructing lesions (3.5 months vs. 10 months, P = 0.001). Female median survival displayed a trend toward shorter survival compared to males (3.5 months vs. 10 months, P = 0.059). There was no statistically significant difference in the percentages of advanced, stage IV disease in the obstructive group and the non-obstructive group (11/32 [34.3%] and 14/37 [37.8%], respectively P = 0.80).

Conclusions: Obstructive esophageal cancers predict shorter median overall survival compared with non-obstructive cancers, without any correlation between obstruction of the lesion and tumor metastatic stage.

Background: Traditionally, transesophageal echocardiography (TEE) has been performed under moderate sedation and local pharyngeal anesthesia. Respiratory complications during the TEE can occur.

Objectives: To test the effectiveness of low-dose midazolam combined with verbal sedation during TEE.

Methods: The study comprised 157 consecutive patients who underwent TEE under mild conscious sedation. All patients received local pharyngeal anesthesia and low doses of midazolam combined with verbal sedation. The course of TEE and clinical characteristics of the patients were analyzed.

Results: The mean age was 64 ± 15.3 years, 96 males (61%). In 6% of the patients, low dose midazolam in combination with verbal sedation was insufficient and propofol was administrated. In women under 65 years of age with normal renal function, there was a 40% risk of low-dose midazolam being ineffective (P = 0.0018).

Conclusions: In most patients, TEE can be conducted easily using low-dose midazolam combined with verbal sedation. Some patients need deeper sedation with anesthetic agents like propofol. These patients tended to be younger, in good general health, and more often female.

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.

Contactin associated protein-like 2 (CASPR2) and leucine-rich glioma-inactivated protein 1 (LGI1) voltage gated potassium channel (VGKC) proteins are found in both the central and peripheral nervous systems [1]. Antibodies against these proteins are associated with encephalopathy, seizures, peripheral nerve hyper-excitability, autonomic dysfunction, hyponatremia, pain, and insomnia in varying severity and combination [1].

Morvan syndrome, first described in 1890, combines symptoms of peripheral nervous system (PNS), central nervous system (CNS), and autonomic nervous system dysfunction. It was later found to be associated with VGKC-complex antibodies, mainly against CASPR2 or LGI1 or both.

Our patient had a history of anti-LGI1 positive limbic encephalitis, which presented years later with anti-CASPR2 positive Morvan syndrome.

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.

Metastatic pulmonary calcinosis (MPC) is characterized by deposits of calcium in normal pulmonary parenchyma. Diffuse pulmonary calcinosis commonly occurs in hypercalcemia and/or hyperphosphatemia and is more commonly related to renal failure than primary hyperparathyroidism, skeletal metastases, or multiple myeloma [1]. Calcium depositions favor alkaline tissue and are thus more common in the upper lobes of the lung, which have a higher ventilation to perfusion ratio and a low capillary pCO₂, resulting in an alkaline pH [2]. Therefore, the most common radiographic manifestation consists of poorly defined nodular opacities bilaterally in the upper lung zones [3].

Background: Massive, non-compressible bleeding is a leading cause of preventable trauma mortality. Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) is a minimally invasive procedure in which a balloon catheter is maneuvered into the aorta to temporarily occlude large vessels and enable stabilization of the exsanguinating patient.

Objectives: To present experiences in assimilating REBOA at a single level 1 trauma center in Israel, to evaluate the technical aspects of the procedure, and to describe patient characteristics and outcomes.

Methods: This retrospective cohort study comprised civilians admitted with hemorrhagic shock to our trauma department who were treated with REBOA between November 2017 and July 2021. Descriptive statistics of the patients, characteristics of the injuries and patient outcomes are presented.

Results: The study included 22 patients (median age 30.1 years, 21 male). The mean systolic blood pressure (SBP) before REBOA inflation was 59.6 ± 11.4 mmHg, and the mean SBP measured after the procedure was 115.2 ± 26.3 mmHg. In 20 patients (91%), the SBP was normalized (> 90 mmHg) shortly after inflation of the balloon, and they survived the treatment in the trauma department; 15 (75%) survived the first 30 days. 

Conclusions: REBOA is an effective method for the initial resuscitation and hemorrhage control of patients with massive, non-compressible bleeding and is relatively easy to assimilate in a hospital. The achievement of immediate normalization of SBP enables medical personnel to correct physiological parameters and obtain accurate imaging before proceeding to the operating theater. 

Late, preterm premature rupture of the membranes (PPROM) presents a major obstetrical challenge balancing between iatrogenic prematurity and risk of prolonged rupture of membranes. In recent years, the pendulum has been shifting toward expectant management until gestation week 37 + 0. We examined the latest guidelines and major trials and summarized optimal management. We addressed the major dilemmas of women with PPROM during gestation weeks 34 + 0 to 36 + 6.

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: Population screening for the BRCA mutations in Ashkenazi Jewish women was recently implemented in Israel and is expected to lead to a 10-fold increase in the diagnosis of asymptomatic carriers. Performing the screening follow-up within multidisciplinary dedicated clinics for carriers is recommended for early detection and risk reduction.

Objectives: To determine the availability, capacity, and practices of dedicated screening clinic for BRCA carriers in Israel.

Methods: A telephone-based survey of all public hospitals in Israel was conducted October 2020 to August 2021 to determine whether they had a dedicated clinic. Dedicated clinics were defined as multidisciplinary screening clinics offering at least breast and gynecological screening and risk reducing services on site. The clinic director or nurse navigator answered a questionnaire about screening practices followed by a semi-structured interview.

Results: Of the ten dedicated BRCA clinics found in Israel, nine participated. Approximately 4500 BRCA carriers are currently being followed. No specialized clinics are available in the southern district or in the northernmost half of the northern district of Israel, leading to a disparity between periphery and center. Screening recommendations, although asserted as adhering to international guidelines, vary among clinics including age at initiating of clinical exam, use of adjunct imaging modalities, and follow-up during lactation and after risk reducing surgery.

Conclusions: There is a suboptimal distribution of dedicated clinics for BRCA carriers in Israel. Nationally centralized attempt to create guidelines that will unify screening practices is warranted, especially considering the expected increase in demand.

Background: Higher body mass index (BMI) has been shown to be a protective factor from mortality in sepsis patients. Yet, whether this effect is different in the very elderly is currently unknown.

Objective: To investigate the relationship between BMI and sepsis outcomes in patients older and younger than 80 years of age.

Methods: A retrospective analysis of consecutive patients admitted with sepsis to Shamir Medical Center, Israel, was conducted. We compared patients older than and younger than 80 years of age with a BMI higher and lower than 25 kg/m² for hospitalization outcomes.

Results: Patients older than 80 years presented with multiple co-morbidities compared to younger patients, but with no difference between BMI groups. Similarly, hospitalization outcomes of functional deterioration, discharge to long-term care facilities, and readmission were not significantly different between BMI groups in the same age category. Mortality was significantly different between BMI groups in patients older than 80 years of age, with higher mortality in BMI < 25 kg/m²: in-hospital mortality (23.4% vs. 14.9%, P < 0.001), 30-day mortality (27.6% vs. 17.9%, P < 0.001), and 90-day mortality (43.4% vs. 28.9%, P < 0.001). This difference was not significant between the groups younger than 80 years old. On logistic regression, BMI over 25 kg/m² was protective in all mortality categories. Nevertheless, there was no significant interaction between age over 80 years to BMI over 25 kg/m² in all mortality outcomes.

Conclusions: Among patients hospitalized with sepsis, higher BMI is a protective factor against mortality in both elderly and younger patients.

Background: The adherence to a narrowband ultraviolet B (NB-UVB) treatment plan is derived, in large part, from the patient’s skin tolerance to the phototherapy dose. At present, the initial and first-month incremental phototherapy doses are determined prior to treatment initiation based on the patient's Fitzpatrick skin phototyping.

Objectives: To identify variables that predict adherence to NB-UVB first-month treatment dosage plan.

Methods: Charts of 1000 consecutive patients receiving NB-UVB at a hospital-based phototherapy unit were retrospectively analyzed. We included patients receiving NB-UVB for atopic dermatitis, psoriasis, vitiligo, and mycosis fungoides. The first-month NB-UVB treatment plan was determined based on the patient's Fitzpatrick phototype. Adherence to treatment was defined as receiving at least 80% of the planned first-month cumulative dose. We compared adherent vs. non-adherent patient groups for age, sex, Fitzpatrick phototype, presence of freckles, nevus count category, and type of dermatological disease.

Results: The study included 817 eligible patients, mean age 40 (2–95) years; 54% men; 32% had Fitzpatrick phototype I-II. Distribution by diagnosis was atopic dermatitis (29%), psoriasis (27%), vitiligo (23%), and mycosis fungoides (21%). Adherence to NB-UVB treatment plan was observed in 71% of patients. Adherence decreased with age, with 7% decrease per year (P = 0.03) and was higher among mycosis fungoides patients (77.3%) compared to all other diagnoses (69.8%; P = 0.02).

Conclusions: Adherence to NB-UVB treatment may be related to age and diagnosis. Fitzpatrick phototype-based first-month treatment plans should be modified accordingly.

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.

Background: Current guidelines for the treatment of heart failure with reduced ejection fraction (HFrEF) are based on studies that have excluded or underrepresented older patients.

Objectives: To assess the value of guideline directed medical therapy (GDMT) in HFrEF patients 80 years of age and older.

Methods: A single-center retrospective study included patients hospitalized with a first and primary diagnosis of acute decompensated heart failure (ADHF) and ejection fraction (EF) of ≤ 40%. Patients 80 years of age and older were stratified into two groups: GDMT, defined as treatment at hospital discharge with at least two drugs of the following groups: beta-blockers, angiotensin converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), or mineralocorticoid antagonists; and a personalized medicine group, which included patients who were treated with up to one of these drug groups. The primary outcomes were 90-day all-cause mortality, 90-day rehospitalization, and 3-years mortality.

Results: The study included 1152 patients with HFrEF. 254 (22%) patients who were at least 80 years old. Of the group, 123 were GDMT at discharge. When GDMT group was compared to the personalized medicine group, there were no statistically significant differences in terms 90-day mortality (17% vs. 13%, P = 0.169), 90-day readmission (51 % vs. 45.6%, P = 0.27), or 3-year mortality (64.5% vs. 63.3%, P = 0.915).

Conclusions: Adherence to guidelines in the older adult population may not have the same effect as in younger patients who were studied in the randomized clinical trials. Larger prospective studies are needed to further address this issue.