Israel Medical Association Journal

Background: Thymectomy is a reliable surgical method for treating patients with myasthenia gravis (MG) and benign tumors of the thymus. Despite the advantages of minimally invasive surgical approaches for resection of thymic neoplasms, there are still controversies regarding the superiority of one type of surgery over another.

Objectives: To report the results of our initial Israeli experience with robotic thymectomy in 22 patients with MG and suspected benign thymic tumors.

Methods: We retrospectively analyzed 22 patients (10 men, 12 women) who underwent robotic thymectomy by a left-sided (16) or right-sided approach (6) using the da Vinci robotic system at Assaf Harofeh Medical Center. Seven patients were diagnosed with MG before surgery and 14 had suspected benign thymic neoplasms.

Results: Average operative time was 90 minutes. There were no deaths or intraoperative complications. Postoperative complications occurred in two patients (dyspnea and pleural effusion). Median blood loss was 12.3 cc (range 5–35 cc), median hospital stay 2.9 days (range 2–5 days), and mean weight of resected thymus 32.1 grams. Seven patients had thymic hyperplasia, six a lipothymoma, one a thymic cyst. Seven each had thymomas in different stages and one had a cavernous hemangioma.

Conclusions: Robotic thymectomy is a safe, technically effective surgical method for resection of thymic neoplasms. The advantages of this technique are safety, short hospitalization period, little blood loss, and low complications. We have included this surgical procedure in our thoracic surgery residency program and recommend a learning curve program of 10 to 12 procedures during residency.

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: When a breast lesion is suspected based on a physical exam, mammography, or ultrasound, a stereotactic core needle biopsy (CNB) is usually performed to help establish a definitive diagnosis. CNBs are far less invasive than excisional biopsies, with no need for general anesthetics or hospitalization, and no recovery period. However, since only samples of the mass are removed in a CNB and not the whole mass, sampling errors can occur.

Objectives: To compare the degree of agreement between the pathological data from CNBs and excisional biopsies from a single tertiary referral hospital.

Methods: The concordance of pathological data was compared in patients who underwent CNBs and had their surgical procedures at the same medical center.

Results: From the 894 patients who underwent CNBs, 254 (28.4%) underwent subsequent excisional biopsies at our medical center. From the total of 894 patients, 227 (25.3%) who underwent a CNB were diagnosed with a malignancy, with the rest of the CNBs being diagnosed as benign pathologies. The pathological findings in the CNBs and in the excisional biopsies concurred in 232/254 (91.3%) of the cases.

Conclusions: A CNB to confirm mammographic or clinical findings of breast lesions is an accurate method to establish a pathological diagnosis of breast lesions. The accuracy is higher for invasive carcinomas than for non-invasive cancers. Excisional biopsies are necessary for lesions with anticipated sampling errors or when the core needle biopsy findings are discordant with clinical or mammographic findings.

Background: Recent studies have analyzed risk factors associated with complications after gastric cancer surgery using the Clavien-Dindo classification (CD). However, they have been based on Asian population cohorts (Chinese, Japanese, Korean).

Objectives: To prospectively analyze all post-gastrectomy complications according to severity using CD classification and identify postoperative risk factors and complications.

Methods: We analyzed all gastrectomies for gastric cancer performed 2009–2014. Recorded parameters included demographic data, existing co-morbidities, neo-adjuvant treatment, intra-operative findings, postoperative course, and histologic findings. Postoperative complications were graded using CD classification.

Results: The study comprised 112 patients who underwent gastrectomy. Mean age was 64.8 ± 12.8 years; 53 patients (47%) underwent gastrectomy, 37 (34%) total gastrectomy, and 22 (19%) total extended gastrectomy. All patients had D2 lymphadenectomy. The average number of retrieved lymph nodes was 35 ± 17. Severe complication rate (≥ IIIa) was 14% and mortality rate was 1.8%. In a univariate analysis, age > 65 years; ASA 3 or higher; chronic renal failure; multi-organ resection; and tumor, node, and metastases (TNM) stage ≥ IIIc were found to be significantly associated with CD complication grade > III (P = 0.01, P = 0.05, P = 0.04, P = 0.04, and P = 0.01, respectively). Multivariate regression analysis revealed advanced stage (≥ IIIc) and age > 65 years to be significant independent risk factors (P < 0.05).

Conclusions: Age > 65 and advanced stage (≥ IIIc) were the primary risk factors for complications of grade > III according to the CD classification following gastrectomy for gastric cancer.

Background: Acute musculoskeletal pain is one of the most commonly reported symptoms among patients visiting the emergency department (ED). Treatment with over-the-counter pain medications, given by nurses, results in improved pain management and reduces the waiting time to drug administration without significant side effects. Opioid analgesics are extensively used for acute pain in the ED. Compared to morphine, oxycodone has a much more specific pharmacological activity, higher analgesic potential, and more tolerable side effects.

Objectives: To assess the degree of pain reduction using different protocols, including dypirone and oxycodone given by nurses, in treating acute musculoskeletal pain in the emergency department (primary outcome) and to evaluate the need for rescue medications (secondary outcome).

Methods: This observational prospective clinical trial compared two groups of 50 patients, each one visiting the ED due to musculoskeletal pain. One group was treated with dipyrone syrup and the other was treated with oxycodone syrup. The primary outcome was pain reduction measured by the Numeric Rating Scale (NRS). The secondary outcome was the difference in need for rescue medications.

Results: The reduction in the NRS was greater in the patients treated with oxycodone. This finding was statistically and clinically significant (P < 0.001). The need for rescue medications was also significantly reduced in this group of patients (P = 0.007).

Conclusions: This study showed that the administration of over-the-counter oxycodone syrup by nurses decreases the post-treatment pain reported by patients, reduces the need for rescue medications, and increases the satisfaction of the medical staff.

Background: Extended-spectrum beta-lactamase (ESBL) production is the most common antimicrobial resistance mechanism in the neonatal intensive care unit (NICU), with colonization and blood stream infections being a major threat to this population. Since 2013, all NICU admissions at our facility were screened twice weekly for ESBL colonization.

Objectives: To determine independent risk factors for colonization of infants with ESBL-producing bacteria in the NICU.

Methods: A retrospective case study of ESBL-colonized infants vs. controls (matched by date of birth and gestational age) was conducted in the NICU of Soroka University Medical Center, Israel, between 2013 and 2014. Epidemiological, laboratory, and clinical data were extracted from medical files. Univariable and multivariable analyses were used to assess associations between ESBL colonization and possible clinical risk factors.

Results: Of 639 admissions during the study period, 87 were found to be ESBL-colonized (case infants) and were matched to 87 controls. Five case infants became infected (5.7%) with ESBL strains. Klebsiella pneumoniae was the most common isolated bacteria. The mean time from admission to colonization was 15 days. Univariable analysis showed an association of male gender and highest Apgar score at 1 and 5 minutes with ESBL colonization (P < 0.05). Multivariable analysis yielded only a possible association of higher Apgar score at 1 and 5 minutes (hazard ratio [HR] 1.515, 95% confidence interval [95%CI] 0.993-2.314; HR 1.603, 95%CI 0.958–2.682, respectively) with ESBL colonization.

Conclusions: Future studies should focus on maternal colonization and possible strategies for preventing vertical transmission of ESBL strains to high-risk neonates.

Background: Idiopathic membranous nephropathy (IMN) is one of the most common causes of nephrotic syndrome (NS) in Caucasian adults. Most patients have good renal prognosis, but 30–40% may progress to end stage renal disease (ESRD). 

Objectives: To evaluate the efficacy and safety of immunosuppressive treatment (IST) in high-risk patients.

Methods: All IMN patients diagnosed by kidney biopsy from 2004–2010 were included. Clinical and laboratory data were collected at each follow-up visit. Risk assessment for renal progression classified patients as high risk if: 24 hour protein excretion > 6 g/day, estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2, and severe disabling or life-threatening clinical symptoms of NS were present.

Results: Among 290 biopsies, 37 patients (12.7%) were IMN. They were allocated to the high-risk IST group (n=16) or low-risk supportive treatment (ST) group (n=21) according to the likelihood of developing renal failure. Mean follow-up was 47 ± 17.3 months. Complete and partial remission rate was 68.7% for high-risk IST vs. 90.4% for low-risk ST. In the high-risk IST group, eGFR was significantly lower at 30 months (65.5 ± 28.6 vs. 85.3 ± 21.6 at baseline, P < 0.05). Four high-risk patients reached ESRD. In the low-risk ST group, eGFR remained stable at 30 and 60 months. 

Conclusions: This study showed a high remission rate for IMN. IST with prednisolone and cyclophosphamide provided favorable renal outcomes in most high-risk patients. The very high remission rate obtained in the low-risk patients confirms the adequacy of supportive treatment in this group.

Background: Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disease with poor prognosis despite intensive therapy.

Objectives: To discuss the ideal therapy of EBV-associated HLH for adults.

Methods: We retrospectively studied 23 adult patients with EBV-associated HLH at our institution between January 2000 and June 2015. The clinical characteristics, treatment, and prognosis of adult EBV-associated HLH were analyzed. The median age was 38 years (range 18–72).

Results: All patients were found to have high fever, thrombocytopenia, abnormal liver function, elevated ferritin, and lactate dehydrogenase. Leukopenia, anemia, coagulopathy, hypofibrinogenemia, and splenomegaly were found in more than 80% of patients. Ten patients were treated with HLH-2004 protocol. Eventually, 95.7% of patients died of EBV-associated HLH. Non-HLH-2004 treatment and bone marrow suppression may predict early relapse independently, and the poor performance status and high lactate dehydrogenase level can be poor prognostic factors. It was also validated in comprehensive analysis of published articles.

Conclusions: Adult EBV-associated HLH occurs most often in people of Asian descent who are older than 35 years. These patients had a disappointing outcome despite intensive treatment, especially with high lactate dehydrogenase levels, poor performance status, and bone marrow suppression. HLH-2004 protocol has shown a glimmer of hope in the adult populations.

Background: Recent evidence suggests that olfaction is impaired in patients with pseudotumor cerebri (PTC).

Objectives: To measure suprathreshold olfactory function by using the University of Pennsylvania Smell Identification Test (UPSIT), assessing its usefulness for routine clinical use.

Methods: Forty PTC patients underwent USPIT olfactory testing.

Results: Twenty-nine out of 40 (73%) PTC patients (36 women, 4 men; mean age 34 years) had reduced suprathreshold smell sensation according to UPSIT scores: 19 (47%) had mild microsmia, 9 (23%) had moderate microsmia, and one (3%) was classified as having severe microsmia. The mean UPSIT score of all patients was 32.4 (95% confidence interval 31.4–33.4). Multivariate regression analysis found that UPSIT scores were not related to disease activity, disease duration, initial intracranial pressure (ICP), or visual function.

Conclusions: Many PTC patients have reduced suprathreshold olfactory dysfunction that can be discovered by UPSIT, a rapidly administered smell test, which is suitable for clinical office use.

Background: Little is known about the incidence of urinary tract infections (UTI) in the dispersed Bedouin population. UTIs are routinely treated empirically according to local resistance patterns, which is important when evaluating the risk factors and antibiotic resistance patterns in the Bedouin population.

Objectives: To analyze risk factors, pathogens, and antibiotic resistance patterns of UTIs in the Bedouin population compared to the general population in southern Israel. To compare data from this study to that from a previous study conducted at our center.

Methods: We prospectively followed all patients hospitalized with community acquired UTIs during a 4 month period at Soroka Medical Center. We also compared results from this study to those from a study conducted in 2000.

Results: The study comprised 223 patients: 44 Bedouin (19.7%), 179 (80.3) non-Bedouin; 158 female (70.9%), 65 male (29.1). The Bedouin were younger (51.7 vs. 71.1 years of age, P < 0.001) and had a lower Charlson Comorbidity Index (2.25 vs. 4.87, P < 0.001). Enterobacteriaceae were the most common pathogens identified, and Escherichia coli (E. coli) was the most common with 156 (70%) strains identified, followed by Klebsiella spp. with 29 (13%), Proteus spp. with 18 (8%), pseudomonas with 9 (4%), and other bacteria including enterococci with 11 (5%). The prevalence of E. coli increased significantly from 56% in 2000 to 70% in this study. We also noted an increase in community acquired extended spectrum beta lactamase (ESBL) pathogens from 4.5% in 2000 to 25.5% in the present study. No statistically significant difference was observed between the Bedouin and general populations in the causal pathogens, resistance to antibiotics, length of therapy, and readmission rate within 60 days. 

Conclusions: The Bedouin population hospitalized for UTIs is younger and presents with fewer co-morbidities. Isolated pathogens were similar to those found in the general population as was the presence of drug resistant infections. Overall, a substantial percentage of pathogens were resistant to standard first-line antibiotics, driving the need to change from empiric therapy to aminoglycoside therapy. 

 

Background: The closure of an atrial septal defect is procedure that is frequently performed in both adults and children. Currently, the most commonly used devices are the Amplatzer® and Occlutech® Figulla® atrial septal occluders. Studies conducted in adults have shown that these devices all have similar performance efficiency for the closure of secundum atrial septal defects. No study to date has examined their performance in the pediatric population.

Objectives: To evaluate and compare the performance of Amplatzer® and Occlutech® Figulla® atrial septal occluders in the pediatric population.

Methods: A consecutive retrospective study of exclusively pediatric patients who underwent percutaneous closure of atrial septal defect with these devices was conducted at our institute. 

Results: The study comprised 110 children, 50 in the Amplatzer® device group and 60 in the Occlutech® Figulla® device group. The groups had similar demographic and defect characteristics, except for defect size per transesophageal echocardiography (TEE), which was 2.1 mm larger in the Amplatzer® device group (P = 0.02). No adverse events were recorded in either of the study groups. Complete defect closure at 12 months follow-up (procedural success) was achieved in all but one of the patients in the Amplatzer® group and all but two in the Figulla® group (P = 1). The residual shunt rates of fenestrated defects were similar in the two groups. 

Conclusions: For children with an isolated secundum atrial septal defect, percutaneous closure is equally safe and effective with either Amplatzer® or Occlutech® Figulla® devices.

Background: Non-infectious uveitis (NIU) leads to severe visual impairment, potentially impacting on health-related quality of life (QoL). 

Objectives: To investigate the impact of NIU on QoL.

Methods: Eighty NIU patients and 23 healthy controls completed the 36-item Short-Form Health Survey (SF)-36. The SF-36 values were statistically analyzed to evaluate differences between patients and healthy controls and to identify correlations between SF-36 subscores and clinical/demographic data. 

Results: NIU patients showed a decrease in the physical component summary score (P < 0.0001) compared to healthy controls, while no difference was highlighted in the mental component summary score (P = 0.97). NIU patients showed a decrease in physical functioning (P = 0.008), role-physical (P = 0.003), bodily pain (P = 0.0001), general health (P < 0.0001), and social functioning (P = 0.01). Physical functioning was lower in patients with acute anterior uveitis (AAU) than in those with panuveitis (P = 0.003). No differences were found between patients with bilateral or unilateral NIU, isolated NIU, or NIU associated with systemic diseases and with or without ocular activity. No correlations were identified between best-corrected visual acuity and SF-36 subscores. Physical functioning (P = 0.02), bodily pain (P = 0.004), and social functioning (P = 0.02) were reduced in males versus females. 

Conclusions: QoL is impaired in individuals with NIU, particularly in the physical domains, general health, and social functioning. AAU affects physical functioning more than panuveitis. NIU seems to affect per se QoL disregarding inflammatory activity, visual impairment, and presence of associated systemic diseases.