Israel Medical Association Journal

Background: Despite its wide use, evidence is inconclusive regarding the effect of percutaneous endoscopic gastrostomy (PEG) in patients with chronic diseases and dementia among hospitalized patients with malnutrition.

Objectives: To examine the effect of PEG insertion on prognosis after the procedure.

Methods: This retrospective analysis of medical records included all adult patients who underwent PEG insertion between 1 January 2009 and 31 December 2013 during their hospitalization. For each PEG patient, two controls similar in age, sex, referring department, and underlying condition were randomly selected from the entire dataset of patients admitted. The effect of PEG on mortality and repeated admissions was examined.

Results: The study comprised 154 patients, 49 referred for PEG insertion and 105 controls (mean age 74.8 ± 19.8 years; 72.7% females; 78.6% admitted to internal medicine units). Compared to controls, the PEG group had a higher 2-year mortality rate (59.2% vs. 17.1%, P < 0.001) but the 2-year readmission rate did not differ significantly (44.9% vs. 56.2% respectively, P = 0.191). Regression analysis showed PEG was  associated with increased risk of the composite endpoint of death or readmission (hazard ratio 1.514, 95% confidence interval 1.016–2.255, P = 0.041). No specific characteristic of admission was associated with increased likelihood of death or readmission. Among readmitted patients, reasons for admission and baseline laboratory data, including albumin and cholesterol, did not differ between the PEG patients and controls.

Conclusions: In-hospital PEG insertion was associated with increased mortality at 2 years but had no effect on readmissions.

The interplay between post-traumatic stress disorder (PTSD) and autoimmunity is well known. One of the contributors leading to immune disorders is autonomic dysregulation, which is characterized by attenuated parasympathetic and elevated sympathetic systems. In this review, we described evidence regarding the relationship between stress, PTSD, autonomic dysfunction, and autoimmunity. Stress is a physiological response, which is functional for our being. The implication of dysfunction in stress response may be a cause of disease development. We described the fundamental role of the pathological high levels of stress in PTSD as a mediator factor that contributes to autonomic dysfunction, which as a result may lead to autoimmunity. Systemic lupus erythematosus, rheumatoid arthritis, and type 1 diabetes are some of the autoimmune diseases PTSD patients are at higher risk of developing. Notably, some autoimmune diseases are shown to increase the susceptibility to develop PTSD, which may indicate a bidirectional influence. In addition, we elaborated on stress as a major component in both fibromyalgia and PTSD, as there are overlaps between the pathogenesis of fibromyalgia and PTSD. Underlying chronic low-grade inflammation, which characterizes PTSD patients, may be a potential target and biomarker in treating PTSD patients. We believe that chronic low-grade inflammation, high concentrations of cytokines, and other inflammatory biomarkers, which characterize PTSD patients, may be potential targets and biomarkers in the treatment of PTSD patients and part of the PTSD diagnostic criteria.

Fibromyalgia is one of the most significant causes of chronic widespread musculoskeletal pain, heavily burdening both individual patients and the healthcare system. Hence, reducing the prevalence of the disorder is of paramount importance. Unfortunately, the etiology and the exact risk factors leading to the development of fibromyalgia are not clearly known, making its prevention difficult and challenging. Nevertheless, there are numerous risk markers that are associated with an increased probability of the disease, such as obesity, psychological and physical stress, exposure to traumatic life events, certain infectious disorders, and co-morbid rheumatic and psychiatric disorders. It is reasonable to assume that targeting preventable risk markers may suppress consequent emergence of fibromyalgia, but studies investigating primary prevention on fibromyalgia are scarce. In this review, we examined several studies that discuss proven methods to prevent fibromyalgia, including maintenance of a normal body mass index, regular physical exercise, and psychological techniques such as cognitive behavioral therapy.

Background: Clinical investigations of long-term effects of coronavirus disease 2019 (COVID-19) are rarely translated to objective findings.

Objectives: To assess the functional capacity of individuals reported on deconditioning that hampered their return to their pre-COVID routine.

Methods: Assessment included the 6-minute walk test (6MWT) and the 30-second sit-to-stand test (30-STST). We compared the expected and observed scores using the Wilcoxon signed-rank test. Predictors of test scores were identified using linear regression models.

Results: We included 49 individuals, of whom 38 (77.6%) were recovering from mild COVID-19. Twenty-seven (55.1%) individuals had a 6MWT score lower than 80% of expected. The average 6MWT scores were 129.5 ± 121.2 meters and 12.2 ± 5.0 repeats lower than expected scores, respectively (P < 0.001 for both). The 6MWT score was 107.3 meters lower for individuals with severe COVID-19 (P = 0.013) and rose by 2.7 meters per each 1% increase in the diffusing capacity of carbon monoxide (P = 0.007). The 30-STST score was 3.0 repeats lower for individuals who reported moderate to severe myalgia (P = 0.038).

Conclusions: Individuals with long COVID who report on deconditioning exhibit significantly decreased physical capacity, even following mild acute illness. Risk factors include severe COVID-19 and impaired diffusing capacity or myalgia during recovery.

Background: The coronavirus disease 2019 (COVID-19) pandemic has severe consequences in terms of mortality and morbidity. Knowledge of factors that impact COVID-19 may be useful in the search for treatments.

Objectives: To determine the effect of glucose-6-phosphate dehydrogenase (G6PD) deficiency on morbidly and mortality associated with COVID-19.

Methods: All patients admitted to Hadassah Hebrew University Medical Center between 01 March 2020 and 03 May 2021 with a diagnosis of COVID-19 were included. We retrospectively retrieved demographic, clinical, and laboratory data from the hospital’s electronic medical records. The main outcomes were mortality, intensive care unit (ICU) admission, and severity of COVID-19.

Results: The presence of G6PD deficiency emerged as an independent protective predictor for ICU admission (odds ratio [OR] 0.258, 95% confidence interval [95%CI] 0.077–0.619, P = 0.003) and the development of critical illness (OR 0.121, 95%CI 0.005–0.545, P = 0.006). Moreover, patients with G6PD deficiency had a trend toward lower mortality rates that did not reach statistical significance (OR 0.541, 95%CI 0.225–1.088, P = 0.10).

Conclusions: Patients with G6PD deficiency were less likely to have a severe disease, had lower rates of ICU admission, and trended toward lower mortality rates.

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: Diagnosis of onychomycosis is based on potassium hydroxide (KOH), direct smear, culture, and polymerase chain reaction. Nail clippings are rarely used as a diagnostic tool.

Objectives: To evaluate nail clippings for the diagnosis of onychomycosis and to compare it to KOH smears.

Methods: Nail clipping specimens of 39 patients were collected: 34 with onychomycosis proved by positive culture and 5 from normal nails. The specimens were submitted to histological processing and then stained with periodic acid–Schiff (PAS) and Grocott-Gomori's methenamine silver (GMS) stains. For each nail, KOH smear was also performed. Two pathologists who had no information on the KOH smear and the culture results evaluated the nail clipping histology for the presence of fungal element. Their assessment was compared to the KOH smear and culture results.

Results: Of the 34 specimens that had positive culture, 25 were dermatophytes, 5 were molds, and 4 were candida. Clipping specimens were positive in 30 cases (88%): 23/25 dermatophyte, 4/5 molds, and 3/4 candida. Pathologists were able to classify the pathogens into dermatophytes and non-dermatophytes based on the morphology. PAS stain results were the same as GMS in evaluation of the nail specimen. KOH smear was positive in 29 nails (85%): 20/25 dermatophytes, all 5 molds, and 4 candida. In all five nails where the culture was negative, both clipping and KOH smear did not show fungal elements.

Conclusion: Nail clippings can serve as a rapid, inexpensive, and reliable method for evaluation of onychomycosis, comparable to KOH smear, with the advantage of pathogen group identification.

Background: Anal squamous cell carcinoma (ASqCC) is a rare malignancy, traditionally treated with combined chemoradiation, with a continuous infusion of 5-fluorouracil (5-FU) and mitomycin C (MMC). Replacing intravenous (IV) 5-FU with oral capecitabine (oral fluoropyrimidine) has been reported as a non-inferior treatment option. However, these data are scarce, with variable results.

Objectives: To examine the outcome of patients with ASqCC treated with either IV 5-FU or capecitabine concomitantly with radiation therapy. To compare treatment side effects, local recurrence, and general outcome.

Methods: We reviewed charts of patients who were diagnosed with stage I–III ASqCC. All participating patients received chemoradiation at the Assuta Medical Center between 2011 and 2019.

Results: In this study, 43 patients with ASqCC were eligible; 14 received 5-FU and 29 were treated with capecitabine. Basic characteristics were similar between the two groups, with longer follow-up for the 5-FU group. Six months following treatment, 100% (13/13 with adequate follow-up) of the 5-FU group had complete clinical response, compared to 84% in the capecitabine group (21/24), P = 0.143. The local recurrence incidence was higher in the 5-FU group at 23% (7, 10, 26 months following therapy, and none in the capecitabine group (P = 0.088). Although local and hematological toxicities were similar between groups, one patient receiving capecitabine died during chemoradiotherapy.

Conclusions: Oral capecitabine demonstrated non-inferior disease control in ASqCC treated with chemoradiotherapy. We recommend oral capecitabine over continuous IV 5-FU in locally and locally advanced ASqCC. Close monitoring of side effects is required to reduce major toxicity.

Background: Pediatric patients with newly diagnosed type 1 diabetes mellitus (T1DM) are commonly treated with daily multiple insulin injections or an insulin pump. They tend to have higher body mass index-standard deviation scores (BMI-SDS) than non-diabetic children.

Objectives: To identify patterns in the changes in BMI in the 3 years after T1DM diagnosis, and to discover factors that relate to excessive weight gain.

Methods: This retrospective study included clinical and laboratory data for 194 boys and girls aged 2–18 years at the time of diagnosis and at 1, 2, and 3 years after. Their BMI values were compared to non-diabetic children using BMI percentile and z-score (standard deviation) based on the U.S. Centers for Disease Control and Prevention (CDC) growth charts.

Results: Both males and females had low mean BMI-SDS at diagnosis (-0.4499 ± 1.38743 male, 0.3050 ± 1.29887 female) that increased after 1 year (-0.0449 ± 1.14772 male, 0.1451 ± 0.98893 female). Lower glycated hemoglobin (HbA1c) at 1 year correlated with higher BMI-SDS (r = -0.215, P = 0.011). No such correlation was found in the following 2 years. The daily dose of basal insulin correlated with higher BMI-SDS at 1 year (r = 0.183, P = 0.026) and 3 years (r = 0.297, P < 0.01). No association was found between the use of an insulin pump or continuous glucose monitoring and higher BMI-SDS.

Conclusions: BMI-SDS of children with T1DM was lower than average at the time of diagnosis and rose higher than average in the 3 years following. Higher BMI-SDS was not significantly associated with sex or ethnicity. The most prominent increase happened in the first year.

Background: Due to the high variability in malignancy rate among cytologically indeterminate thyroid nodules (Bethesda categories III–V), the American Thyroid Association recommends that each center define its own categorical cancer risk.

Objectives: To assess cancer risk in patients with cytologically indeterminate thyroid nodules who were operated at our center.

Methods: In a retrospective study, we analyzed the pathology results of all the patients whose fine needle aspiration results showed Bethesda III–V cytology and who subsequently underwent total thyroidectomy or lobectomy from December 2013 to September 2017.

Results: We analyzed 56 patients with indeterminate cytology on fine needle aspiration. Twenty-nine (52%) were defined as Bethesda III, 19 (34%) Bethesda IV, and 8 (14%) Bethesda V category. Malignancy rates were 38%, 58%, and 100% for Bethesda categories III, IV, and V, respectively. Most malignancies in Bethesda categories III and IV were follicular in origin (follicular thyroid carcinoma and follicular type papillary thyroid carcinoma), while 100% of the patients with Bethesda category V were diagnosed with classical papillary thyroid carcinoma. No correlation was found between sonographic and cytological criteria of nodules with Bethesda categories III and IV and rates of malignancy.

Conclusions: We found higher than expected rates of malignancy in indeterminate cytology. This finding reinforces the guidelines of the American Thyroid Association to establish local malignancy rates for thyroid nodules with indetermined cytology.

Takotsubo syndrome (TTS) often develops following stressors such as cardiac surgery. It may be fatal in rare cases. Our 70-year-old female patient presented with a rare case of tricuspid valve papillary fibroelastoma, which was complicated by fatal TTS after successful resection. The patient had a right atrial mass that was investigated with computed tomography and transesophageal echocardiography (TTE). She was scheduled for surgery. Pathology findings were consistent with papillary fibroelastoma of the tricuspid valve. Three weeks after successful surgery, the patient was admitted due to cardiogenic shock with echocardiographic findings of apical ballooning and left ventricular outflow tract obstruction consistent with TTS. The patient died one hour after her admission despite optimal medical therapy.

Leonardo da Vinci was a man of art and science. He became the archetype of the Renaissance era. Leonardo exhaustively studied the proportions of the body, drawing Vitruvian Man in 1490. It is regarded as a universal cultural icon. Leonardo's anatomical illustrations were of notable precision, and he is still considered as the pioneer of modern anatomy. We focus on Leonardo's masterpiece Virgin of the Rocks, which displays the intersection between his prodigious artistic talent and his commitment to science. This master painting discloses discordance between the artist's vast anatomical knowledge and its actualization in the painting. Consequently, many enigmas arise: How could the expert of anatomy, considered as the canon man of proportions, paint anatomical errors and why did he not actualize his knowledge in the painting? Was this an error or intentional? Could the painting techniques he used explain optical illusions that distorted the images? Was he so far ahead of his time that he did not feel compelled to paint realistically, but rather preferred to let his imagination and creativity run free? Some 500 years after Leonardo da Vinci's death, there is no one answer, but there is room for much speculation.

Background: Polyp detection rate (PDR) is a convenient quality measure indicator. Many factors influence PDR, including the patient's background, age, referral (ambulatory or hospitalized), and bowel cleansing.

Objectives: To evaluate whether years of professional experience have any effect on PDR.

Methods: A multivariate analysis of a retrospective cohort was performed, where both patient- and examiner-related variables, including the experience of doctors and nurses, were evaluated. PDR, as the dependent variable was calculated separately for all (APDR), proximal (PPDR), and small (SPDR) polyps.

Results: Between 1998 and 2019, 20,996 patients underwent colonoscopy at a single center. After controlling for covariates, the experience of both doctors and nurses was not found to be associated with APDR (odds ratio [OR] 0.99, 95% confidence interval [95%CI] 0.98–1.00, P = 0.15 and OR 1.03, 95%CI 1.02–1.04, P < 0.0001, respectively). However, after 2.4 years of colonoscopy experience for doctors, and 9.5 years of experience for nurses, a significant increase in APDR was observed. Furthermore, results revealed no association for PPDR and SPDR, as well.

Conclusions: Years of colonoscopy experience for both doctors and assisting nurses were not associated with APDR, PPDR, and SPDR. In doctors with 2.4 years of experience and nurses with 9.5 years of experience, a significant increase in APDR was observed.

Background: Advances in examination techniques have improved routine assessment of non-gynecological structures in the pelvis.

Objectives: To describe the sonographic features of incidental urological abnormalities found during gynecological transvaginal ultrasound.

Methods: A retrospective descriptive analysis of patients who underwent gynecological ultrasound and were diagnosed with urologic findings was performed. The sonographic features of the findings including size, echogenicity, and vascularity were examined.

Results: Gynecological ultrasound diagnosed urological findings in nine women. Two had primary neoplasms of the urinary bladder, one had metastases to the urinary bladder, one had polyps in the distal ureters, four presented with calculus in the distal ureters (one of them was 19 weeks pregnant), and one showed diverticulum of the urethra. At presentation five women (56%) had urinary complaints. Two patients (22%) with abdominal pain with distal ureteral calculi had normal transabdominal ultrasound targeted to the urinary system prior to the gynecological sonography.

Conclusions: Transvaginal ultrasound is useful in the diagnosis of urological abnormalities, mainly in the urinary bladder and the distal ureters. We suggest adding transvaginal assessment for female patients with urinary complains in whom transabdominal ultrasound of urinary system was unremarkable.

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.