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עמוד בית
Tue, 05.12.23

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October 2023
Rotem Tal-Ben Ishay MD MPH, Kobi Faierstein MD, Haim Mayan MD, Noya Shilo MD

Background: At the beginning of 2020, the coronavirus disease 2019 (COVID-19) pandemic presented a new burden on healthcare systems.

Objectives: To evaluate the impact of the COVID-19 pandemic on the outcome of non-COVID patients in Israel.

Methods: We conducted a retrospective observational cohort study at a tertiary medical center in Israel. From December 2018 until June 2022, 6796 patients were hospitalized in the internal medicine wards. Patients were grouped based on their admission date: admitted during COVID waves (waves group), admitted between waves (interim group), and admitted during the same months in the previous year (former-year group).

Results: Mortality during hospitalization and 30-day mortality were higher in the waves group compared to the interim and former-year groups (41.4% vs. 30.5% and 24%, 19.4% vs. 17.9% and 12.9%, P < 0.001). In addition, 1-year mortality was higher in the interim group than in the waves and former-year group (39.1 % vs. 32.5% and 33.4%, P = 0.002). There were significant differences in the readmissions, both at 1 year and total number. The waves group had higher rates of mechanical ventilation and noradrenaline administration during hospitalization. Moreover, the waves group exhibited higher troponin levels, lower hemoglobin levels, and more abnormalities in liver and kidney function.

Conclusions: Hospitalized non-COVID patients experienced worse outcomes during the peaks of the pandemic compared to the nadirs and the preceding year, perhaps due to the limited availability of resources. These results underscore the importance of preparing for large-scale threats and implementing effective resource allocation policies.

Moran Drucker Iarovich MD, Sara Apter MD, Eli Konen MD MHA, Yael Inbar MD, Marrianne Michal Amitai MD, Eyal Klang MD

Background: Computed tomography (CT) is the main diagnostic modality for detecting pancreatic adenocarcinoma.

Objectives: To assess the frequency of missed pancreatic adenocarcinoma on CT scans according to different CT protocols.

Methods: The medical records of consecutive pancreatic adenocarcinoma patients were retrospectively collected (12/2011–12/2015). Patients with abdominal CT scans performed up to a year prior to cancer diagnosis were included. Two radiologists registered the presence of radiological signs of missed cancers. The frequency of missed cancers was compared between portal and pancreatic/triphasic CT protocols.

Results: Overall, 180 CT scans of pancreatic adenocarcinoma patients performed prior to cancer diagnosis were retrieved; 126/180 (70.0%) were conducted using pancreatic/triphasic protocols and 54/180 (30.0%) used portal protocols. The overall frequency of missed cancers was 6/180 (3.3%) in our study population. The frequency of missed cancers was higher with the portal CT protocols compared to the pancreatic/triphasic protocols: 5/54 (9.3%) vs. 1/126 (0.8%), P = 0.01. CT signs of missed cancers included small hypodense lesions, peri-pancreatic fat stranding, and dilated pancreatic duct with a cut-off sign.

Conclusions: The frequency of missed pancreatic adenocarcinoma is higher on portal CT protocols. Physicians should consider the cancer miss rate on different CT protocols.

September 2023
Ljudmila Stojanovich PhD, Natasa Stanisavljevic PhD, Aleksandra Djokovic PhD, Milomir Milanovic PHD, Jovica Saponjski PhD, Yehuda Shoenfeld MD FRCP MaACR

Background: Data are scarce on the immunogenicity of coronavirus disease 2019 vaccines in patients with autoimmune rheumatic diseases (ARD).

Objectives: To measure the immunoglobulin G (IgG) response after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization and to evaluate clinical characteristics associated with seropositivity.

Methods: Samples were collected after the second and third doses of the three different types of vaccines in ARD patients. Seroconversion rates and IgG antibody S1/S2 titers were measured.

Results: The type of ARD diagnosis and previous treatment had no significant impact on the serum IgG antibody levels measured after the second (P = 0.489 and P = 0.330, respectively) and boost dose (P = 0.441 and P = 0.446, respectively). What made a significant difference regarding serum IgG antibody levels after the second dose was the type of SARS-CoV-2 vaccine. The difference was highly statistically significant for all vaccine types (P = 0.001 with the highest odds ratio for the mRNA vaccine). After the boost with the mRNA vaccine, all patients achieved a high level of serum IgG antibody levels (t = 10.31, P = 0.001). No ARD patients experienced serious post-vaccinal reactions. Eight patients developed COVID-19 before the boost dose.

Conclusions: In ARDs patients, the highest level of serum IgG antibody against S1/S2 proteins was achieved with the mRNA vaccine, irrespective of the therapy applied or the type of the disease. We recommend a booster dose with mRNA vaccine in all ARDs for the highest SARS-CoV-2 protection without serious post-vaccinal reactions observed.

Avishay Elis MD, Ella Giladi MD, Ahmad Raiyan MD, Alaa Atamna MD

Background: Congestive heart failure (CHF) with reduced ejection fraction (HFrEF) or with preserved ejection fraction (HFpEF) is a common diagnosis in patients hospitalized in the department of internal medicine. Recently, the therapeutic regimens were updated, as the sodium-glucose cotransporter-2 (SGLT2) inhibitors became an integral part of the therapeutic regimen for either HFrEF or HFpEF.

Objectives: To define the demographic and clinical characteristics of CHF patients hospitalized in the department of medicine.

Methods: We conducted a retrospective cohort study that included all patients hospitalized in the departments of medicine at the Rabin Medical Center, Israel, between 2016 and 2019. Demographic and clinical background, in-hospital procedures, discharge regimens, and outcome parameters were evaluated according to HFrEF/HFpEF.

Results: The cohort included 4458 patients. The majority (97%) presented with a preexisting diagnosis, whereas HF was an active condition in only half of them. The rates of HFrEF/HFpEF were equal. In most cases, the trigger of the exacerbation could not be determined; however, infection was the most common cause. There were basic differences in the demography, clinical aspects, and therapeutic regimens at discharge between HFrEF and HFpEF. Both conditions were associated with high in hospital mortality (8%) and re-admissions rates (30 days [20%], 90 days [35%]) without any difference between them.

Conclusions: HFrEF/HFpEF patients differed by demographics and co-morbidities. They were equally represented among patients admitted to medical wards and had similar prognosis. For both diagnoses, hospitalization should be considered for updating therapeutic regimens, especially with SGLT2 inhibitors.

August 2023
Sheer Shabat MD, Ronit Grinbaum MD, Yoram Kluger MD, Haggi Mazeh MD, Zvi Ackerman MD, Orit Pappo MD, Offir Ben-Ishay MD

Background: Signet ring cell carcinoma (SRCC) is classified as an undifferentiated gastric carcinoma with poor prognosis. Early SRCCs are associated with improved prognosis.

Objectives: To describe the outcomes of incidental SRCC.

Methods: In this case series, 900 medical charts of patients with SRCC were screened to identify patients with incidental SRCC, defined as diagnosed in random, non-focal-lesion-targeted biopsies.

Results: Six patients were diagnosed with incidental SRCC and underwent gastrectomy. The final pathology of five patients revealed one or more small foci of early SRCC without lymphovascular invasion. Only one patient had no evidence of malignancy. The median follow-up after surgery was 4.2 years (50 months, range 37–90 months). No deaths or recurrences were recorded during the follow-up period. These results resemble the reported survival rate for early SRCC.

Conclusions: An aggressive surgical approach in incidental gastric SRCC patients is recommended, as they have a chance for long-term survival.

July 2023
Moran Drucker Iarovich MD, Yael Inbar, MD, Sara Apter MD, Eli Konen MD MHA, Eyal Klang MD, Marrianne Michal Amitai MD

Background: Perivascular cuffing as the sole imaging manifestation of pancreatic ductal adenocarcinoma (PDAC) is an under-recognized entity.

Objectives: To present this rare finding and differentiate it from retroperitoneal fibrosis and vasculitis.

Methods: Patients with abdominal vasculature cuffing were retrospectively collected (January 2011 to September 2017). We evaluated vessels involved, wall thickness, length of involvement and extra-vascular manifestations.

Results: Fourteen patients with perivascular cuffing were retrieved: three with celiac and superior mesenteric artery (SMA) perivascular cuffing as the only manifestation of surgically proven PDAC, seven with abdominal vasculitis, and four with retroperitoneal fibrosis. PDAC patients exhibited perivascular cuffing of either or both celiac and SMA (3/3). Vasculitis patients showed aortitis with or without iliac or SMA cuffing (3/7) or cuffing of either or both celiac and SMA (4/7). Retroperitoneal fibrosis involved the aorta (4/4), common iliac (4/4), and renal arteries (2/4). Hydronephrosis was present in 3/4 of retroperitoneal fibrosis patients. PDAC and vasculitis demonstrated reduced wall thickness in comparison to retroperitoneal fibrosis (PDAC: 1.0 ± 0.2 cm, vasculitis: 1.2 ± 0.5 cm, retroperitoneal fibrosis: 2.4 ± 0.4 cm; P = 0.002). There was no significant difference in length of vascular involvement (PDAC: 6.3 ± 2.1 cm, vasculitis: 7.1 ± 2.6 cm, retroperitoneal fibrosis: 8.7 ± 0.5 cm).

Conclusions: Celiac and SMA perivascular cuffing can be the sole finding in PDAC and may be indistinguishable from vasculitis. This entity may differ from retroperitoneal fibrosis as it spares the aorta, iliac, and renal arteries and demonstrates thinner walls and no hydronephrosis.

June 2023
Tal Bechor Ariel MD, Ben Ariel MD, Yuni Lahav MD, Moshe Yana BSc, Michael Ben-Acon MD, Nechama Sharon MD

Background: Infants younger than 6 months of age are not eligible for coronavirus disease 2019 (COVID-19) vaccinations. Maternal variables during pregnancy and the postnatal period may affect the clinical and laboratory course of COVID-19 positive infants.

Objective: To assess the clinical manifestation and laboratory differences in infants with three maternal variables: breastfeeding, vaccinated, and co-illness.

Methods: We conducted a single-center retrospective cohort study of positive COVID-19 infants with three subgroups of maternal variables. The population included infants under 6 months of age hospitalized due to COVID-19. Data about clinical features, laboratory tests, and maternal information including vaccination status, breastfeeding status and maternal positive COVID-19 infection was gathered. All variables were compared among the three subgroups.

Results: Breastfed infants had shorter hospitalization period (mean 2.61 ± 1.378 days) compared to non-breastfed infants (mean 3.8 ± 1.549) (P = 0.051). COVID-19 infants of positive COVID-19 mothers had a higher absolute neutrophil count (mean 4.4 ± 3.8) compared to infants of COVID-19 negative mothers (mean 2.7 ± 2.4) (P = 0.042).

Conclusion: Breastfeeding was associated with shorter periods of hospitalization in COVID-19 positive infants. In addition, positive COVID-19 infants of mothers who were positive for COVID-19 are likely to have a higher absolute neutrophils count.

Yaron Niv MD FACG AGAF, Theodore Rokkas MD PhD FACG AGAF FEBGH

Background: Mucins, heavily glycosylated glycoproteins, are synthesized by mucosal surfaces and play an important role in healthy and malignant states. Changes in mucin synthesis, expression, and secretion may be a primary event or may be secondary to inflammation and carcinogenesis.

Objectives: To assess current knowledge of mucin expression in the small bowel of celiac disease (CD) patients and to determine possible associations between mucin profile and gluten-free diet.

Method: Medical literature searches of articles in English were conducted using the terms mucin and celiac. Observational studies were included. Pooled odds ratios and 95% confidence intervals were calculated.

Results: Of 31 articles initially generated by a literature search, 4 observational studies that fulfilled the inclusion criteria remained eligible for meta-analysis. These studies included 182 patients and 148 controls from four countries (Finland, Japan, Sweden, United States). Mucin expression was significantly increased in small bowel mucosa of CD patients than in normal small bowel mucosa (odds ratio [OR] 7.974, 95% confidence interval [95%CI] (1.599–39.763), P = 0.011] (random-effect model). Heterogeneity was significant: Q = 35.743, df (Q) = 7, P < 0.0001, I2 = 80.416%. ORs for MUC2 and MUC5AC expression in the small bowel mucosa of untreated CD patients were 8.837, 95%CI 0.222–352.283, P = 0.247 and 21.429, 95%CI 3.883–118.255, P < 0.0001, respectively.

Conclusions: Expression of certain mucin genes in the small bowel mucosa of CD patients is increased and may serve as a diagnostic tool and assist in surveillance programs.

May 2023
Yaniv Zager MD, Yuri Goldes MD, Dan Assaf MD, Nadav Zilka MD, Roi Anteby MD, Yehonatan Nevo MD, Liran Barda MD, Avinoam Nevler MD

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.

Mailam Eltity MD, Merav Ben-David MD, Vera Nikitin MD, Amir Dori MD PhD

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.

Daniel Leshin-Carmel MD, Aino Shperber MD, Inessa Minz MD, David Hassin MD, Daniel Starobin MD

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].

March 2023
Abedallh Hamad MD, Frida Shemesh MD, Avi Ohry MD, Yekaterina Slutzky MD, Valeria Kaplan RN MA, Svetlana Kartoon MD, Raphael Joseph Heruti MD

Stevens-Johnson Syndrome (SJS), or toxic epidermal necrolysis, is a rare syndrome that develops after an allergic reaction to a medication [1,2]. It affects the skin and the mucocutaneous tissue. Individuals diagnosed with SJS are rarely referred to a rehabilitation medicine (RM) facility.

The annual prevalence of SJS is about one in one million. The skin is covered with blisters. Usually, it affects about 10 % of body surface area. The patients are treated usually by ophthalmologists, dermatologists, allergologists, and immunologists. When severe complications occur, plastic surgeons and intensive care physicians may also be involved. Few publications were found that linked SJS with comprehensive rehabilitation treatment [3-5].

February 2023
Daniel Solomon MD, Itzhak Greemland MD, Nikolai Menasherov MD, Vyacheslav Bard MD

Background: Surgical resection is the only curative option for gastric carcinoma (GC). Minimally invasive techniques are gaining popularity.

Objectives: To present a single-surgeon's experience in transitioning from an open to a minimally invasive approach, focusing on surgical and oncological outcomes.

Methods: We conducted a retrospective analysis including distal gastrectomy patients 2012–2020 operated by a single surgeon. Two cohorts were compared: open (ODG) and laparoscopic distal gastrectomy (LDG).

Results: Overall, 173 patients were referred for gastrectomy during the study years. We excluded 80 patients because they presented with non-GC tumors, underwent proximal or total gastrectomy, or underwent palliative surgery. Neoadjuvant treatment was administered to 62 patients (33.3%). Billroth 1 was the preferred method of reconstruction (n=77, 82.8%), followed by Roux-en-Y (n=12, 13%). Fifty-one patients (54.8%) underwent LDG, 42 (45.2%) underwent ODG. The LDG group had significantly shorter lengths of stay (6 days, interquartile range [IQR] 1–3 5–8 vs. 5 days, IQR 1–3 4–6, P = 0.001, respectively), earlier return to oral feeding (1 day, IQR 1–3 1–3 vs. 2 days, IQR 1–3 1–3.2, P < 0.001), and earlier removal of drains (4 days, IQR 1–3 3–5.2 vs. 5 days, IQR 1–3 3.5–6.7, P < 0.001). Overall lymph node yield was 30 (IQR 1–3 24–39) and was similar among groups (P = 0.647).

Conclusions: Laparoscopic techniques for resection of distal GC are feasible and safe, leading to good perioperative outcomes and adequate lymph node yield.

Shir Schlosser BMedSc, Svetlana Zalmanov MD, Raphael M. Pfeffer MD, Yoav Lipski MD, Vladislav Grinberg MD, Yael Kalmus RN, Daphne Levin PhD, Keren Hod RD PhD, Merav A. Ben David MD

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.

Baruch Wolach MD, Ziv Lenzner MD

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.

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