Israel Medical Association Journal

Background: Patients with mechanical prosthetic heart valves must be treated with vitamin K antagonists (VKA) due to an increased risk of valve thrombosis and systemic embolism.

Objectives: To assess the effects of the COVID-19 pandemic on VKA treatment control in patients with mechanical prosthetic heart valves.

Methods: We conducted a retrospective nationwide cohort study using the Clalit Health Services database. The cohort included patients who underwent either aortic or mitral valve replacement using a prosthetic mechanical valve. The primary outcomes included the overall time in therapeutic range (TTR) and the percent of patients with a TTR < 50% during the first year of the COVID-19 pandemic compared to preceding year.

Results: The cohort included 2381 patients. The percentage of patients who had at least two international normalized ratio (INR) tests during the first year of the COVID-19 pandemic was significantly lower compared to the year preceding the pandemic (81% and 87%, respectively, P < 0.001). In both years, the percentage of patients without any documented INR test was high (31.5% in the first COVID-19 pandemic year and 28.9% in the preceding year, P < 0.001). TTR was significantly lower during the 1st year of the COVID-19 pandemic compared to the preceding year (68.1% ± 26 and 69.4% ± 24, P = 0.03). A TTR > 50% was demonstrated in 78% and 81% during the pandemic and the preceding year, P = 0.009.

Conclusions: We noted overall poor VKA control in patients with mechanical heart valves. During the COVID-19 pandemic, VKA control became even worse as reflected by significantly lower TTR and INR tests rates.

Background: Galactin-3 has been found to be involved in oocyte maturation, folliculogenesis, implantation, and placentation. The expression of Galactin-3 in the endometrium of women who have successfully undergone in vitro fertilization (IVF) has been suggested as a potential biomarker for predicting successful embryo implantation.

Objectives: To evaluate the expression of Galactin-3 in the sera and follicular fluid of women during IVF cycles.

Methods: This prospective research included 21 women undergoing IVF treatments. Blood samples were taken at four points: day 2 before starting stimulation, trigger day, day of oocyte retrieval, and day of the β-human chorionic gonadotropin level test. In addition, follicular fluid samples were taken on the day of oocyte retrieval. Galactin-3 protein levels were measured in serum and follicular fluid using enzyme-linked immunosorbent assay.

Results: Galactin-3 levels on the stimulation day were positively correlated to estradiol levels on the day of the trigger (0.59, P = 0.02). Among women who achieved pregnancy compared to those who did not, Galectin-3 serum levels were higher on the day of the trigger (17.93 ± 4.35 ng/ml vs. 11.01 ± 3.73 ng/ml, P = 0.015).

Conclusions: These findings may imply a potential role of Galectin-3 on the success of IVF treatments, underscoring the potential importance of inflammatory processes in fertility.

Background: Coronary heart disease (CHD) patients are considered high cardiovascular risks. Guidelines recommend low-density lipoprotein cholesterol (LDL-C) target levels below 55 mg/dl with > 50% reduction from baselines. These levels can be reached by a combination of statins, ezetimibe, and anti-protein convertase subtilisin/kexin type 9 (anti-PCSK9) agents. Our clinical impression was that CHD patients do not reach LDL-C target levels, despite the wide availability.

Objectives: To evaluate whether hospitalization would result in changes in lipid lowering regimens and short-term compliance.

Methods: We conducted a retrospective cohort study using data of CHD patients who were admitted to internal medicine wards at Clalit Health Services medical centers because of anginal syndrome during 2020–2022. The data were evaluated for demographic and clinical characteristics; LDL-C level at admission, 6 months previously, and 3 months and 6–9 months after discharge; rates of reaching LDL-C target levels; and lipid lowering treatment at admission, discharge, and 6–9 months after.

Results: The cohort included 10,540 patients. One-third and three-quarters did not have lipids level measurements up to 6 months before and during hospitalization, respectively. Only one-fifth of the patients reached LDL-C values before and during admission (median LDL-C 72 mg/dl; range 53–101). Approximately half were treated with high-dose potent statins. Only 10% were treated with ezetimibe. Hospitalization did not have a clinically significant effect on short-term lipid lowering treatment or LDL-C levels.

Conclusions: Gaps were noted between guidelines and clinical practice for reaching LDL-C target levels. Further education and strict policy are needed.

Background: Preeclampsia is a unique vascular disease during pregnancy that generally appears after 20 of weeks gestation or until 6 weeks after delivery. Left undiagnosed, preeclampsia can lead rapidly to death of both mother and fetus.

Objectives: To verify the efficacy of peripheral blood inflammatory markers (BIMs)in diagnosing preeclampsia and compare them with results from other studies.

Methods: Our retrospective case-control study comprised two patient groups. Pregnant women with preeclampsia and pregnant women without preeclampsia were compared for BIMs: neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and mean platelet volume (MPV). The primary endpoint of our research was to assess the predictive power of BIMs for preeclampsia diagnosis.

Results: The sample size was calculated based on expected differences of BIMs between the control and study groups. Comparison of quantitative variables was conducted with independent sample t-test or alternatively by Wilcoxon rank sum test. The MPV values were slightly higher in the preeclampsia group, but not statistically significant. NLR and PLR did differentiate between study and control groups.

Conclusions: The diagnostic accuracy of BIMs is unsatisfactory for preeclampsia diagnosis. Discrepancies concerning these values need to be clarified. Further large prospective studies are necessary to validate the potential factor accuracy in preeclampsia diagnosis.

Background: Heart failure (HF) is an emerging pandemic associated with increased mortality, recurrent hospitalizations, and reduced quality of life. Guideline-directed medical therapy has been shown to improve outcomes, particularly in patients with HF with reduced ejection fraction (HFrEF). The main goal of HF clinics is optimizing medical therapy.

Objectives: To assess the impact of our HF clinic on medical therapy and clinical outcomes.

Methods: We obtained demographic, echocardiographic, and clinical data of patients listed in our HF clinic during a 4-year period. Medical therapy was evaluated based on patient reports and documented data. Recurrent admissions for HF were documented.

Results: A total of 317 patients (74.1% male, median age 66 years, IQR 55–74) were listed in the clinic with a total of 1140 visits. Of these patients, 62.5% had HFrEF, 20.5% presented with mildly reduced ejection fraction, and 17% showed preserved ejection fraction at the time of the first visit. The use of sodium glucose co-transporter 2 inhibitors and mineralocorticoid receptor antagonists was optimized in 92% and 91% of the patients, respectively. In the subgroup of patients with HFrEF, the use of angiotensin-receptor antagonist/neprilysin inhibitor increased from 22.6% to 87.9% (P < 0.001) and SGLT2 inhibitor use increased from 49.2% to 92% (P < 0.001). During the follow-up period (2.2 years, IQR 1.1–3.1), 203 patients (64%) were readmitted to the hospital for HF at least once. The rate of readmissions decreased over time.

Conclusions: An HF clinic plays an important role in optimizing medical therapy and reducing readmissions.

The prevalence of difficult-to-treat rheumatoid arthritis (D2T RA) varies between 5% and 25%, with females comprising the majority of patients and no difference in patient age between D2T and non-D2T RA cohorts. While several attempts to subclassify D2T RA patients into defined subgroups have been tried, the inclusion of an individual D2T RA patient to one of the predefined subgroups can be difficult or impossible as multiple factors are usually involved in the mechanisms of rheumatoid arthritis (RA) refractoriness, with the complex interplay of inflammatory, structural, social, and psychological factors being unique for each patient. More severe disease at presentation, including seropositivity and early erosion formation, and insufficiently aggressive initial treatment can both contribute to the eventual development of D2T RA. No single test or study can replace the holistic clinical approach to the diagnosis and understanding of the causation of D2T RA. Traditional in-depth clinical history and thorough clinical examination remain sine qua non in managing D2T RA patients. Multifaceted contributions of inflammatory and non-inflammatory components create the uniqueness of D2T RA and dictate a comprehensive approach to the management, including both pharmacologic and non-pharmacological therapeutic strategies. Mean annual total costs for D2T RA patients have been estimated as being about twice as high as that of patients with non-D2T RA.

The emergence of the hybrid hospital represents a paradigm shift, blending the physical and virtual realms to optimize healthcare delivery. Telehealth made its significant entrance into the health systems during the coronavirus disease 2019 (COVID-19) pandemic. The use of a variety of telehealth initiatives increased during the COVID-19 pandemic. Approximately 8% of primary care visits in the United States are by telehealth. Despite the rapid growth of telehealth, several barriers persist. Technological limitations, regulatory challenges, and resistance to change among both healthcare providers and patients pose hurdles to the widespread adoption of telehealth services. A significant concern in the healthcare digital evolution is the digital divide. Socioeconomic factors, such as limited access to high-speed internet and digital devices, can exacerbate existing healthcare disparities. An important part of the hybrid hospital is home hospitalization, which is an alternative to regular hospitalization. This method opens access to big, tertiary, academic centers to remote populations and advances treatment equity. Home hospitalization has become available in several countries such as Australia, China, and the United States, with impressive results for peripheral, remote populations. According to the McKenzie Report, virtual hospitals have the potential to ease busy health systems, make more hospital beds available, decrease the need for building physical hospitals, and save millions of dollars. Hybrid hospitals and telehealth are here to stay. The medical community should study the risks and opportunities and establish guidelines for proper, quality, and safe management.

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: Exclusive breastfeeding is recommended through six months as it supports infant growth and development. Yet, many mothers do not exclusively breastfeed in early postpartum.

Objectives: To examine factors associated with exclusive breastfeeding at hospital discharge among culturally diverse women.

Methods: This cross-sectional study used data of women who gave birth at a major medical center in Israel in 2015–2017. Descriptive statistics and regression analysis were conducted to examine maternal characteristics and associated breastfeeding outcomes by hospital discharge.

Results: Among 10,978 women, 17.8% (n=1958) exclusively breastfed, 57.9% (n=6357) partially breastfed, and 24.3% (n=2663) did not breastfeed. Among Israeli-born and former Soviet Union-born Jewish women, breastfeeding intention (odds ratio [OR] 19.59, 95% confidence interval [95%CI] 10.27–37.35 and OR 15.92, 95%CI 5.79–43.80, respectively) and early breastfeeding (OR 2.415, 95%CI 1.91–3.05 and OR 2.04, 95%CI 1.57–2.64, respectively) were associated with exclusive breastfeeding. The only significant factor associated with exclusive breastfeeding among refugees and Israeli-born Muslim women was early breastfeeding (OR 1.61, 95%CI 1.20–2.16). For Ethiopian-born Jewish women, not married (OR 0.330, 95%CI 0.114–0.955) and cesarean delivery (OR 0.481, 95%CI 0.232–0.998) were negatively associated with exclusive breastfeeding.

Conclusions: Despite having access to the same hospital-based breastfeeding support, there were differences among ethno-culturally diverse women in Israel. In this study, we identified maternal characteristics associated with early breastfeeding among women of diverse ethno-cultural backgrounds. Study findings highlight the importance of ethno-cultural considerations in breastfeeding practices and inform health professionals of factors associated with exclusive breastfeeding in early postpartum.

Background: Intra-articular knee injections (IAKI) are commonly used for diagnostic and therapeutic purposes but may induce anxiety and fear. While existing literature has identified the variance between expected and actual pain levels in various medical procedures, this phenomenon remains unexplored in the context of IAKI.

Objectives: To describe the differences between anticipated and experienced pain recorded during IAKI.

Methods: The study cohort included 50 patients who underwent IAKI by an orthopedic specialist in an outpatient clinic. Patients recruited to the study recorded the anticipated and experienced pain, anxiety index, and factors influencing injection related fear.

Results: The study population (n=50) demonstrated a significant difference between the pain expected before the injection (mean Visual Analogue Scale [VAS] score 6.19) and the actual experienced (mean VAS score 2.07, P-value < 0.001). Significant differences between anticipated and experienced VAS scores were demonstrated for both females and males. There was a significant difference between males and females in terms of estimated VAS score. There was no significant difference between males and females in term of the experienced VAS score. The difference (delta) between expected and experienced pain differed significantly between sexes.

Conclusions: These findings emphasize the importance of educating patients about expected pain levels during IAKI. Presenting this quantified information may reassure patients that the procedure is not as painful as expected, which can potentially increase the compliance.

Background: Left ventricular assist devices (LVAD) are a staple element in contemporary treatment of advanced heart failure. LVAD surgeries are mostly done in heart transplantations centers, as a destination therapy or as a bridge to heart transplantation.

Objectives: To describe our step-by-step experience in establishing and implementing a new LVAD program in a non-heart transplant center. To give insight to our short- and long-term results of our first 25 LVAD patients.

Methods: Preliminary steps included identifying the need for a new program and establishing the leading team. Next is defining protocols for pre-operative evaluation, operating room, post-operative management, and outpatient follow-up. The leading team needs to educate other relevant units in the hospital that will be involved in the care of these patients. It is essential to work in collaboration with a heart transplant center from the very beginning. Patient selection is of major importance especially in the early experience. Initially “low risk” patients should be enrolled.

Results: We describe our first 25 LVAD patients. Our first five patients all survived beyond 2 years, with no major complications. Overall, there was one operative death due to massive GI bleeding. There were four late deaths due to septic events.

Conclusions: Establishing a new LVAD program can be successful also with small- and medium-size programs. With careful and meticulous planning LVAD implantation can be extended to more centers thus offering an excellent solution for advanced heart failure patients.

Background: Immunoglobulin G4-related disease (IgG4-RD) is a chronic, immune-mediated condition characterized by fibro-inflammatory lesions with lymphoplasmacytic infiltration. Diagnosis traditionally relies on histopathological findings, including the presence of IgG4+ plasma cells. However, due to challenges in biopsy accessibility, additional measures are needed to facilitate diagnosis.

Objectives: To identify additional parameters for characterizing IgG4-RD patients.

Methods: We compared several circulating factors between a cohort of patients with IgG4-RD disease seen at our hospital between 2017 and 2023 and healthy controls.

Results: Among 16 suspected patients, 13 were confirmed to have IgG4-RD, and 3 were classified as highly likely. Comparison with controls revealed differences in white blood cell count (WBC) (Folf change (FC) 1.46, P < 0.05), plasmablasts (FC 3.76, P< 0.05), plasmablasts CD38 (FC 1.43, P < 0.05), and CD27 (FC 0.66, P = 0.054), thus highlighting potential markers for IgG4-RD diagnosis. Treatments with steroids/rituximab tend to reduce plasmablast (FC 0.6) and IgG4 (FC 0.28) levels and to increase Gal-3 levels.

Conclusions: Levels of plasmablasts are a significant diagnostic feature in IgG4-RD. Healthy individuals have a lower level of plasmablasts. Elevated Gal-3 in serum of patients with IgG4-RD suggests a role in plasmablast activation. CD38/CD27 expression by plasmablasts emerges as a potential marker. Further research on a larger cohort is needed to confirm these findings.

Among patients admitted with acute decompensated heart failure (ADHF), deterioration of renal function with resulting acute kidney injury (AKI) is reported in up to 70% of patients with cardiogenic shock. Twenty percent of heart failure patients with AKI progress to dialysis (AKI-D). Optimal timing for initiation of renal replacement therapies (RRT) has been researched; however, minimal studies discuss guidelines for weaning from RRT [1]. Electronic monitoring of urine output (UO) may serve as a tool to aid in withdrawal from RRT. We present a case of ADHF with severe AKI requiring continuous renal replacement therapy (CRRT) where real-time electronic monitoring of UO was implemented for the first time to guide de-escalation therapy from CRRT until successful withdrawal.

Background: Long-term support with a HeartMate 3 (HM3) left ventricular assist device (LVAD) has improved outcomes of patients with end-stage heart failure. However, there is a paucity of data on the outcomes of patients who underwent concomitant cardiac surgical procedure (CCSP) during HM3-LVAD implantation.

Objectives: To assess our single-center experience with patients who underwent CCSP during the implantation of an HM3-LVAD.

Methods: From December 2016 until April 2022, 131 adult patients underwent HM3-LVAD implantation. A total of 23 patients underwent CCSP during the HM3-LVAD implantation+CCSP, and 108 underwent only HM3-LVAD implantation (HM3-only).

Results: The median age was 59 ± 11 years (range 54-67), 82% (n=108) were male, and 76% (n=100) were implanted as a bridge-to-transplant. The concomitant procedures performed during the implantation included 8 aortic valve repairs/replacements, 14 tricuspid valve repairs, 4 patent foramen ovales or atrial septal defect closures, and 3 other cardiac procedures. The mean cardiopulmonary bypass time was 113 ± 58 minutes for the HM3-only group and 155 ± 47 minutes for the HM3+CCSP group (P = 0.007). The mortality rates at 30 days, 6 months, and 12 months post-implantation were 2 (9%), 5 (22%), and 6 (26%) respectively for the HM3+CCSP group, and 7 (6%), 18 (17%), and 30 (28%) for the HM3-only group (P = 0.658, 0.554, and 1.000).

Conclusions: Our experience demonstrated no significant difference in the 30-day, 6-month, and 12-month mortality rates for patients who underwent a CCSP during HM3-LVAD implantation compared to patients who did not undergo CCSP during HM3-LVAD implantation.

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.