Israel Medical Association Journal

Background: Endothelial progenitor cells may have a role in ongoing endothelial repair. Impaired mobilization or depletion of these cells may contribute to progression of vascular disease. Our hypothesis was that endothelial progenitor cells would be suppressed in patients with acute cerebrovascular event based on our previous study that found severe endothelial dysfunction in those patients.

Objectives: To study the ability of patients with acute stroke to build colonies of endothelial progenitor cells.

Methods: We studied the number of colony-forming units of endothelial progenitor cells (CFU-EPCs) from the peripheral blood of 22 male patients with a first-time acute stroke (age 58.09 ± 9.8 years) and 13 healthy men (34 ± 6.7 years), 8 female patients with a first-time acute stroke (54.6 ± 10.3 years) and 6 healthy women (38.3 ± 11.6 years). Endothelium-dependent function was assessed by high-resolution ultrasonography of the brachial artery that measured the change in diameter of the artery by flow-mediated diameter percent change (FMD%). All patients had strokes demonstrated by a brain computed tomography (CT) scan done on admission. Peripheral blood was drawn soon after admission and was processed for endothelial progenitor cells in culture.

Results: Thirty patients without known cardiovascular risk factors and who did not take any medications were admitted with a first-time acute stroke. All demonstrated a strong correlation between CFU-EPCs grown in culture and endothelial dysfunction (r = 0.827, P < 0.01). Endothelial dysfunction with an FMD% of -2.2 ± 9.7% was noted in male patients vs. 17.5 ± 6.8% in healthy males (P = 0.0001), and -7.2 ± 10.1% in female patients vs. 25.1 ± 7.1% in healthy females (P = 0.0001). CFU-EPCs were 5.5 ± 6.3 in men with stroke vs. 23.75 ± 5.3 in healthy males (P = 0.0001), and 7.6 ± 4.9 in women with stroke vs. 22.25 ± 6.7 in healthy females (P = 0.0004).

Conclusions: Patients with acute stroke had an impaired ability to grow CFU-EPCs in culture and exhibited endothelial dysfunction. The novelty of this study was the discovery of the phenomenon of depressed numbers of EPCs and the poor ability to grow colonies of EPCs in the first 24 hours of the cerebrovascular event.

Background: Brain-derived neurotrophic factor (BDNF) is a neuronal growth factor that is important for the development, maintenance, and repair of the peripheral nervous system. The BDNF gene commonly carries a single nucleotide polymorphism (Val66Met-SNP), which affects the cellular distribution and activity-dependent secretion of BDNF in neuronal cells.

Objectives: To check the association between BDNF Val66Met-SNP as a predisposition that enhances the development of chemotherapy-induced peripheral neuropathy in an Israeli cohort of patients with breast cancer who were treated with paclitaxel.

Methods: Peripheral neuropathy symptoms were assessed and graded at baseline, before beginning treatment, and during the treatment protocol in 35 patients, using the reduced version of the Total Neuropathy Score (TNSr). Allelic discrimination of BDNF polymorphism was determined in the patients' peripheral blood by established polymerase chain reaction and Sanger sequencing.

Results: We found Val/Val in 20 patients (57.14%), Val/Met in 15 patients (42.86%), and Met/Met in none of the patients (0%). Baseline TNSr scores were higher in Met-BDNF patients compared to Val-BDNF patients. The maximal TNSr scores that developed during the follow-up in Met-BDNF patients were higher than in Val-BDNF patients. However, exclusion of patients with pre-existing peripheral neuropathy from the analysis resulted in equivalent maximal TNSr scores in Met-BDNF and Val-BDNF patients.

Conclusions: These observations suggest that BDNF Val66met-SNP has no detectable effect on the peripheral neuropathy that is induced by paclitaxel. The significance of BDNF Val66Met-SNP in pre-existing peripheral neuropathy-related conditions, such as diabetes, should be further investigated.

Background: Early identification of patients with a likelihood of cardiac improvement has important implications for management strategies.

Objectives: To evaluate whether tissue Doppler imaging (TDI) and two-dimensional (2D) strain measures may predict left ventricular (LV) improvement in patients with recent onset dilated cardiomyopathy (ROCM).

Methods: Clinical and comprehensive echo were performed at baseline and at 6 months. Patients who achieved an increase of ≥ 10 LV ejection fraction (LVEF) units and LV reverse remodeling (LVRR) (group 1) and those who improved beyond the device threshold achieving LVEF of ≥ 0.40 (group 2) were compared to patients who did not improve to this level.

Results: Among 37 patients with ROCM (mean age 56.3 ± 12.9 years and LVEF 29.1 ± 7.0%), 48% achieved LVEF ≥ 0.40 and 37.8% demonstrated LVRR. Patients with LVEF improvement ≥ 40% presented at diagnosis with higher LVEF (P = 0.006), smaller LV end-diastolic diameter (LVEDd) (P = 0.04), higher E’ septal (P = 0.02), lower E/E’ ratio (P = 0.02), increased circumferential strain (P = 0.04), and apical rotation (P = 0.009). Apical rotation and LVEDd were found to be independent predictors of LVRR. End-systolic LV volume was a significant predictor of LVEF improvement (≥ 40%).

Conclusions: Nearly half of the patients with ROCM demonstrated cardiac function improvement beyond the device threshold by 6 months. Apical rotation was introduced in our study as 2D strain prognostic parameter and found to be an independent predictor of LVRR. LV size and volume were predictors of LV improvement.

Background: Sepsis is a common cause of hospitalization, particularly in intensive care units (ICUs), and is a major cause of morbidity and mortality. Diagnosis is often difficult due to the absence of characteristic clinical signs (e.g., fever and leukocytosis); therefore, additional markers, in addition to C-reactive protein (CRP) and white blood cell (WBC) count, are needed.

Objectives: To prospectively link resting energy expenditure (REE) with CRP, WBC count, and sequential organ failure assessment (SOFA) scores in ICU patients. Such a correlation may suggest REE measurement as an additional parameter for sepsis diagnosis.

Methods: Our study comprised 41 ventilated consecutive patients > 18 years of age. Patient demographic data, height, actual body weight, and SOFA scores were collected at admission. REE was measured by indirect calorimetry. REE, CRP, and WBC measurements were collected at admission, on day three after admission, and 1 week later or as clinically indicated.

Results: Comparison of the REE and CRP changes revealed a significant correlation between REE and CRP changes (r = 0.422, P = 0.007). In addition, CRP changes also correlated with the changes in REE (r = 0.36, P = 0.02). Although no significant correlations in REE, WBC count, and SOFA score were found, a significant trend was observed.

Conclusions: To the best of our knowledge, this is the first study to link REE and CRP levels, indicative of severe infection. Further study is needed to establish these findings.

Background: Unlike the elective treatment of metastatic colorectal cancer (MCRC), sufficient data and consensual guidelines on acute care are lacking.

Objectives: To analyze a cohort of MCRC patients who required urgent surgery due to acute abdomen and to identify risk factors contributing to the patient's perioperative mortality and morbidity.

Methods: A retrospective analysis was conducted of patients diagnosed with stage IV colorectal cancer who required urgent laparotomy at the Rabin Medical Center. Comparative analysis was performed using Pearson’s chi-square and Student`s t-test.

Results: Between 2010 and 2015, 113 patients underwent urgent laparotomy due to colorectal cancer complications, of which 62 patients were found to have a metastatic, stage IV, disease. Large bowel obstruction was the most common indication for urgent laparotomy. In-hospital mortality was 30% (n=19), and overall 30 day mortality was 43%. Fifteen patients (24%) required more than one surgery. The average length of hospital stay was 21 days. Age and lactate levels at presentation were the only prognostic factor found for mortality (P < 0.05).

Conclusions: MCRC laparotomy patients incur a significant burden of care and have a relatively high incidence of early mortality. Our data suggest high, verging on unacceptable, mortality and complication rates in this subgroup of patients. This finding is further accentuated in the subgroup of older patients presenting with lactatemia. These data should be considered by surgeons when discussing treatment options with patients and families.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a challenging nosocomial pathogen in the last 50 years.

Objectives: To describe an investigation and containment of an MRSA outbreak in a neonatal intensive care unit (NICU).

Methods: Our NICU is a 25-bed level III unit. Almost 540 neonates are admitted yearly. The index case was an 8 day old term baby. MRSA was isolated from his conjunctiva. Immediate infection control measures were instituted, including separation of MRSA+ carriers, strict isolation, separate nursing teams, and screening of all infants for MRSA. Healthcare workers and parents of positive cases were screened and re-educated in infection control measures. New admissions were accepted to a clean room and visiting was restricted. MRSA isolates were collected for molecular testing.

Results: MRSA was isolated from five infants by nasal and rectal swabs, including the index case. Screening of healthcare workers and families was negative. Two MRSA+ patients already known in the pediatric intensive care unit (PICU) located near the NICU were suspected of being the source. All NICU isolates were identical by pulsed-field gel electrophoresis but were different from the two PICU isolates. The NICU and one of the PICU isolates were defined as ST-5 strain by multilocus sequence typing. One PICU isolate was ST-627. All NICU isolates were Panton–Valentine leukocidin negative and SCCmec type IV. No further cases were detected, and no active infections occurred.

Conclusions: A strict infection control policy and active screening are essential in aborting outbreaks of MRSA in the NICU.

Background: Risk factors for bleeding complications after percutaneous kidney biopsy (PKB) and the role of primary hemostasis screening are not well established.

Objectives: To determine the role of primary hemostasis screening and complication outcomes among individuals who underwent PKB.

Methods: We reviewed data of 456 patients who underwent PKB from 2010 to 2016 in a large university hospital. In 2015, bleeding time (BT) testing was replaced by light transmission aggregometry (LTA) as a pre-PKB screening test.

Results: Of the 370 patients who underwent pre-PKB hemostasis screening by BT testing, prolonged BT was observed in 42 (11.3%). Of the 86 who underwent LTA, an abnormal response was observed in 14 (16.3%). Overall, 155 (34.0%) patients experienced bleeding: 145 (31.8%) had minor events (hemoglobin fall of 1–2 g/dl, macroscopic hematuria, perinephric hematoma without the need for transfusion or intervention) and 17 (3.7%) had major events (hemoglobin fall > 2 g/dl, blood transfusion or further intervention). Abnormal LTA response did not correlate with bleeding (P = 0.80). In multivariate analysis, only prolonged BT (P = 0.0001) and larger needle size (P = 0.005) were identified as independent predictors of bleeding.

Conclusions: Bleeding complications following PKB were common and mostly minor, and the risk of major bleeding was low. Larger needle size and prolonged BT were associated with a higher bleeding risk. Due to the relatively low risk of major bleeding and lack of benefit of prophylactic intervention, the use of pre-PKB hemostasis screening remains unestablished.

Background: Family physicians and internal medicine specialists play an essential role in treating cancer patients. Modern technological advances in radiotherapy are not widely appreciated by primary care physicians. Bone metastases are a frequent complication of cancer. Palliative radiation therapy, as a component of modern advances in radiation treatments, should not subject normal bodily structures to excessive doses of irradiation. The sacrum is a common destination site for bone metastases, yet its concave shape along with its proximity to the rectum, intestines, and femoral heads creates treatment-planning challenges.

Objectives: To investigated whether the volumetric modulated arc therapy (VMAT) technique is preferable to more conventional radiation strategies.

Methods: The study comprised 22 patients with sacral metastases who were consecutively treated between 2013 and 2014. Two plans were generated for the comparison: three-dimensional (3D) and VMAT.

Results: The planning target volume (PTV) coverage of the sacrum was identical in VMAT and 3D planning. The median values for the rectal dose for 3D and VMAT were 11.34 ± 5.14 Gy and 7.7 ± 2.76 Gy, respectively. Distal sacral involvement (S4 and S5) was observed in only 2 of 22 cases, while the upper pole of the rectum ended at the level above S3 in just 3 cases.

Conclusions: Radiation therapy continues to be an integral component of the palliative armamentarium against painful metastases. Radiation oncologist, in conjunction with referral physicians, can tailor treatment plans to reflect the needs of a given patient.

Background: Diffuse large B-cell lymphoma (DLBCL) accounts for 30% of all non-Hodgkin lymphomas (NHL) and 80% of agressive lymphomas. Besides the traditional International Prognostic Index (IPI), some other factors may also influence the prognosis of DLBCL patients.

Objectives: To study how the genetic polymorphisms in the metabolic pathway influence the event-free and overall survivals and therapeutic responses in DLBCL.

Methods: The study was comprised of 51 patients (32 men, 19 women). The average age was 53.1 years. DLBCL was diagnosed between 2011 and 2016 and the average follow-up time was 3.78 years. These patients received 1–8 cycles (an average of 6.2 cycles) of rituximab, cyclophosphamide, doxorubicin, vincristin, prednisolon (R-CHOP) immunochemotherapy. Real-time polymerase chain reaction was used to determine the genetic polymorphisms of CYP2E1, GSTP1, NAT1, and NAT2 genes.

Results: Our results showed that the polymorphisms of CYP2E1, GSTP1, and NAT1 genes did not influence the prognosis of DLBCL patients significantly. In terms of the NAT2 gene, GG homozygous patients showed slightly better therapeutic response and survival results compared to those bearing an A allele; however, the differences were not statistically significant.

Conclusions: Our results could not confirm that genetic polymorphism in metabolic pathways has any predictive role in DLBCL. 

 

Background: Male infertility is solely responsible for approximately 20% of all infertility in couples. Various factors have been proposed as having a negative effect on sperm quality; however, the reasons for the global decline in sperm parameters during the last few decades are still controversial. 

Objectives: To investigate the fluctuations of semen parameters (sperm concentration, motility, and morphology) in three sperm quality groups and to examine the trends of those parameters in the same men over time. 

Results: Our data showed deterioration in all semen parameters assessed in the group of men originally considered as having normal semen values according to the 2010 criteria of the World Health Organization. In contrast, we found significant improvement over time in all semen parameters in the group of men with severe oligo-terato-asthenozoospermia. 

Conclusions: Our results suggest that, although there were changes in sperm quality over time in the groups assessed, the clinical significance is negligible and does not necessarily justify a change in the therapeutic approach to infertility or sperm cryopreservation. 

 

Background: Accurate pulse oximetry reading at hospital admission is of utmost importance, mainly for patients presenting with hypoxemia. Nevertheless, there is no accepted or evidence-based protocol for such structured measuring.

Objectives: To devise and assess a structured protocol intended to increase the accuracy of pulse oximetry measurement at hospital admission.

Methods: The authors performed a prospective comparison of protocol-based pulse-oximetry measurement with non-protocol based readings in consecutive patients at hospital admission. They also calculated the relative percentage of improvement for each patient (before and after protocol implementation) as a fraction of the change in peripheral capillary oxygen saturation (SpO₂) from 100%.

Results: A total of 460 patients were recruited during a 6 month period. Implementation of a structured measurement protocol significantly changed saturation values. The SpO₂ values of 24.7% of all study participants increased after protocol implementation (ranging from 1% to 21% increase in SpO₂ values). Among hypoxemic patients (initial SpO₂ < 90%), protocol implementation had a greater impact on final SpO₂ measurements, increasing their median SpO₂ readings by 4% (3–8% interquartile range; P < 0.05). Among this study population, 50% of the cohort improved by 17% of their overall potential and 25% improved by 50% of their overall improvement potential. As for patients presenting with hypoxemia, the median improvement was 31% of their overall SpO₂ potential.

Conclusions: Structured, protocol based pulse-oximetry may improve measurement accuracy and reliability. The authors suggest that implementation of such protocols may improve the management of hypoxemic patients.