Israel Medical Association Journal

Background: Diabetic ketoacidosis (DKA) poses a significant medical emergency in both type 1 (T1DM) and type 2 diabetes mellitus (T2DM) patients. Recent attention has focused on the emergence of euglycemic DKA associated with sodium-glucose cotransporter-2 (SGLT2) inhibitors.

Objectives: To understand the epidemiology and outcomes of DKA, particularly in T2DM patients.

Methods: We conducted a retrospective cohort analysis of 204 patients admitted with DKA to Shamir Medical Center (2013–2021). We assessed demographics, clinical characteristics, and outcomes. Patients were stratified by diabetes type and SGLT2 inhibitor treatment status.

Results: Among the 204 patients with DKA, 38.2% had T2DM. Patients with T2DM exhibited older age, higher co-morbidity burden, and greater prevalence of microvascular complications compared to T1DM patients. Mortality rates were notably higher among T2DM patients, despite similar DKA severity at presentation, including in-hospital mortality rates of 6.4% vs. 0%, P < 0.05, and 90-day mortality rates of 7.7% vs. 0%, P < 0.05. T2DM was independently associated with adverse hospitalization outcomes, including a composite of rehospitalization, prolonged hospital stays, and mortality (odds ratio 2.68, 95% confidence interval 1.302–5.557). SGLT2 inhibitor treatment did not affect hospitalization outcomes of patients with T2DM.

Conclusions: Our findings underscore the importance of recognizing DKA as a substantial complication in diabetic patients, particularly those with T2DM. Vigilance in management, adherence to DKA guidelines, and awareness of triggers such as SGLT2 inhibitors are crucial for improving outcomes in this population.

Echinococcus infections of the liver and lungs are well-known, but cardiac echinococcus is rare, requiring further understanding. A 19-year-old male presented with chest pain, shortness of breath and palpitations. Changes in an electrocardiogram, increased troponin, and a computed tomography (CT) scan revealed a cardiac cyst at the left ventricle’s posterior lateral wall. Medical management included albendazole and praziquantel for 2 weeks followed by surgical cyst removal.

Clinical presentation of cardiac involvement of echinococcus granulosis is variable, requiring high clinical suspicion. Cardiac CT scan and echocardiography provided sufficient information for the diagnosis. The treatment included surgical removal of the cyst and albendazole administration.

Hydatid cyst is a rare zoonotic disease caused by the parasite Echinococcus granulosus [1]. The incidence in endemic areas is about 1–200 cases per 100,000 in population [2].

The liver (60–70% of cases) and lungs (20–30%) are the most common locations of hydatid cysts, with rare cardiac involvement of only 0.05% to 2% of all cases [3], with the left ventricle most frequently involved (60%) [2,4].

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.

Background: Most dyspneic patients in internal medicine departments have co-morbidities that interfere with the clinical diagnosis. The role of brain natriuretic peptide (BNP) levels is well-established in the acute setting but not in hospitalized patients.

Objectives: To evaluate the additive value of BNP tests in patients with dyspnea admitted to medical wards who did not respond to initial treatment.

Methods: We searched the records of patients who were hospitalized in the department of internal medicine D at Sheba Medical Center during 2012 and were tested for BNP in the ward. Data collected included co-morbidity, medical treatments, diagnosis at presentation and discharge, lab results including BNP, re-hospitalization, and mortality at one year following hospitalization.

Results: BNP results were found for 169 patients. BNP was taken 1.7 ± 2.7 days after hospitalization. According to BNP levels, dividing the patients into tertiles revealed three equally distributed groups with a distinctive character. The higher tertile was associated with higher rates of cardiac co-morbidities, including heart failure, but not chronic obstructive pulmonary disease. Higher BNP levels were related to one-year re-hospitalization and mortality. In addition, higher BNP levels were associated with higher rates of in-admission diagnosis change.

Conclusions: BNP levels during hospitalization in internal medicine wards are significantly related to cardiac illness, the existence of heart failure, and patient prognosis. Thus, BNP can be a useful tool in managing dyspneic patients in this setting.

Background: Hypomagnesemia (serum magnesium level < 1.7 mg/dl) occurs more frequently in patients with type 2 diabetes mellitus (T2DM).Serum magnesium levels are not routinely tested in hospitalized patients, including in hospitalized patients with T2DM.

Objectives: To evaluate the prevalence of hypomagnesemia among hospitalized T2DM patients treated with proton pump inhibitors (PPIs) and/or diuretics.

Methods: A total of 263 T2DM patients hospitalized in general departments were included in the study and were further divided into four groups: group 1 (patients not treated with PPIs or diuretics), group 2 (patients treated with PPIs), group 3 (patients treated with diuretics), and group 4 (patients treated with both PPIs and diuretics).  Blood and urine samples were taken during the first 24 hours of admission. Electrocardiogram was performed on admission.

Results: Of the 263 T2DM patients, 58 (22.1%) had hypomagnesemia (serum magnesium level < 1.7 mg/dl). Patients in group 2 had the lowest mean serum magnesium level (1.79 mg/dl ± 0.27). Relatively more patients with hypomagnesemia were found in group 2 compared to the other groups, although a statistically significant difference was not observed. Significantly more patients in group 3 and 4 had chronic renal failure. Patients with hypomagnesemia had significantly lower serum calcium levels.

Conclusions: Hospitalized T2DM patients under PPI therapy are at risk for hypomagnesemia and hypocalcemia

Background: Otogenic cerebral sinus vein thrombosis (CSVT) is a rare but severe complication of otitis media in children. To date, the role of prothrombotic evaluation is still controversial.

Objectives: To report the clinical manifestations, prothrombotic evaluation, and current management of CSVT.

Methods: We performed a retrospective study of nine pediatric patients with otogenic CSVT who underwent prothrombotic evaluation between 2008 and 2018.

Results: Prominent clinical features included persistent otorrhea (88.8%), signs of mastoiditis (88.8%), high fever ≥ 38.3°C (100%), a classic spiking fever pattern (55.5%), and neurological signs (55.5%). A subperiosteal abscess (66.6%) was the most common otitis media complication associated with mastoiditis and CSVT. No microorganism was identified in 55.5% of patients. Cultures collected from ear secretions had a low yield (6.25%). However, PCR assays had a high detection rate (100%; n=3). The prothrombotic evaluation demonstrated an abnormal LAC–dRVVT ratio (6/9), elevated Factor VIII (5/8) (and a combination of both in four patients), antiphospholipid antibodies (2/8), and high homocysteine levels (1/5).The surgical intervention of choice included one-sided mastoidectomy with myringotomy and ventilation-tube placement on the affected side (77.7%). There were no mortalities and no long-term sequela except chronic otitis media (22.2%).

Conclusions: Our findings demonstrate good outcomes for otogenic CSVT treatment with intravenous antibiotics, anticoagulation, and conservative surgical intervention, which supports the current trend in management. The prothrombotic evaluation revealed transient inflammation-related risk factors but did not alter management. Further prospective multicenter studies are needed to determine its relevance

Background: An association was shown between thrombocytosis and future development of several cancers.

Objectives: To investigate whether pre-treatment platelet counts correlated with clinical outcomes of patients with breast cancer.

Methods: This retrospective study included 22 patients who had been diagnosed with stage I breast cancer and were 66.8 ± 13.2 years of age. Of these, 22 with stage II were 61.6 ± 12.3 years old and 9 with stage III and IV were 64.4 ± 15.3 years old. Clinical and hematological data from the first visit to the oncology clinic were collected. The follow-up period was 12 months to 5 years.

Results: A significant difference in platelet counts was found between patients who died (187,000 ± 4000 µ/L) and those who were disease free for 5 years (248,000 ± 83,000 µ/L, P = 0.0001). A significant difference in platelet-to-lymphocyte ratio was found between patients who died and those with recurrence (192 ± 81 vs. 124 ± 71, P = 0.01). A negative correlation was found between age and lymph nodes (Ps = -0.305, P = 0.02) and staging and white blood cells count (Ps = -0.280, P = 0.04). A positive correlation was found between clinical staging and lymph nodes (Ps = 0.443, P = 0.001) and clinical staging and metastases (P = 0.308, P = 0.02).

Conclusions: Platelet counts may be a prognostic marker for breast cancer. Patients who died within 1 year had lower pre-treatment platelet count, which could represent an insidious disseminated intravascular coagulopathy cancer related consumption process.

Background: Immune thrombocytopenia (ITP) is an autoimmune disorder of variable origin that results in bleeding and decreased platelet count. Autoimmune abnormalities have been described in patients with malignancies including non-Hodgkin's lymphoma but are rarely described in patients with Hodgkin's lymphoma.

Objectives: To describe an unusual presentation of Hodgkin's lymphoma in an unusual age and alarm pediatricians of the challenging diagnosis.  

Methods: We present two cases that highlight an unusual clinical presentation of childhood Hodgkin's lymphoma occurring at an atypical age.

Results: Over a 4-year period, two children aged 5 and 6 years were admitted for suspected ITP, both had cervical lymphadenopathy. Bone marrow examination showed no evidence of tumor or fibrosis. Biopsy of the lymph node was possible only after administration of intravenous immunoglobulins and normalization of the platelet count. Platelet counts increased after initiation of chemotherapy.

Conclusions: The identification of the clinical presentation of ITP as a possible presentation of Hodgkin's lymphoma is important to facilitate timely diagnosis and management.

Background: Statins and selective serotonin reuptake inhibitors (SSRIs) have beneficial effects on health outcomes in the general population. Their effect on survival in debilitated nursing home residents is unknown.

Objectives: To assess the relationships between statins, SSRIs, and survival of nursing home residents.

Methods: Baseline patient characteristics, including chronic medications, were recorded. The association of 5-year survival with different variables was analyzed. A sub-group analysis of survival was performed according to baseline treatment with statins and/or SSRIs.

Results: The study comprised 993 residents from 6 nursing homes. Of them, 285 were males (29%), 750 (75%) were fully dependent, and 243 (25%) were mobile demented. Mean age was 85 ± 7.6 years (range 65–108). After 5 years follow-up, the mortality rate was 81%. Analysis by sub-groups showed longer survival among older adults treated with only statins (hazard ratio [HR] for death 0.68, 95% confidence intervals [95%CI] 0.49–0.94) or only SSRIs (HR 0.6, 95%CI 0.45–0.81), with the longest survival among those taking both statins and SSRIs (HR 0.41, 95%CI 0.25–0.67) and shortest among residents not taking statins or SSRIs (P < 0.001). The survival benefit remained significant after adjusting for age and after conducting a multivariate analysis adjusted for sex, functional status, body mass index, mini-mental state examination, feeding status, arrhythmia, diabetes mellitus, chronic kidney disease, and hemato-oncological diagnosis.

Conclusion: Treatment with statins and/or SSRIs at baseline was associated with longer survival in debilitated nursing home residents and should not be deprived from these patients, if medically indicated. 

Background: Fetal alcohol spectrum disorder (FASD) may be under-recognized and under-diagnosed in Israel. Fewer than 10 FASD diagnoses were reported between 1998 and 2007; however, several hundred diagnoses have been made since. Furthermore, less than 10% of surveyed Israeli pediatricians reported adequate knowledge of FASD.

Objectives: To determine the prevalence of suspected FASD, to establish a database as a starting point for epidemiological studies, and to develop FASD awareness for health, social, and educational services.

Methods: A chart review was conducted at an educational facility for children and adolescents with behavioral and learning challenges. The following information was extracted: adoption status, history of alcohol/drug abuse in the biological mother, medical diagnoses, medication use, and information regarding impairment in 14 published neurobehavioral categories. Subjects were classified as: category 1 (highly likely FASD) – impairment in three or more neurobehavioral categories and evidence of maternal alcohol abuse was available; category 2 (possible FASD) – impairment in three or more neurobehavioral categories and evidence to support maternal substance abuse (type/time unspecified); and category 3 (unconfirmed likelihood of FASD) – impairment in three or more neurobehavioral categories and no information regarding the biological family.

Results: Of 237 files analyzed, 38 subjects (16%) had suspected FASD: 10 subjects (4%) in category 1, 5 (2%) in category 2, and 23 (10%) in category 3. Twenty-seven subjects with suspected FASD (69%) had been adopted.

Conclusions: This study is the most comprehensive review of FASD among Israeli children and adolescents in a population with learning and behavior challenges.

Background: Basal-bolus (BB) insulin treatment is increasingly used in poorly controlled diabetes patients during hospitalization and is commonly recommended at discharge; however, the extent of adherence with this recommendation is unknown.

Objectives: To determine short-term adherence of type 2 diabetes mellitus (T2DM) patients discharged from internal medicine wards with recommendation for BB insulin treatment.

Methods: Prescription (primary physician adherence) and purchase (patient adherence) of long-acting and short-acting insulins during the first month following discharge from internal medicine wards was determined in 153 T2DM patients. Adherence was defined as full if prescription/purchase of both basal (long-acting) and bolus (short-acting) insulin was completed, and as partial if only one kind of insulin (basal or bolus) was prescribed/purchased. Association between demographic and clinical parameters and adherence was determined.

Results: Full adherence with discharge instructions was higher for primary physicians than for patients )79.1% vs. 69.3%, respectively, P = 0.0182). Pre-hospitalization hemoglobin A1C was significantly associated with adherence by both patients and primary physicians (full-adherence group 9.04% ± 2.04%; no-adherence group 7.51% ± 1.35%, P = 0.002). Age was negatively associated with adherence of both primary physicians and patients; however, this association did not reach statistical significance. Patients with certain background diseases such as atrial fibrillation, coronary heart disease, and chronic heart failure had significantly worse adherence (P < 0.05). When the sole cause of admission was diabetes, full adherence (100%) of both primary physicians and patients was found.

Conclusions: Short-term adherence with discharge recommendation for BB insulin treatment is associated with pre-hospitalization patient characteristics.

Background: Previous surveys demonstrated variations in the clinical practices relating to the treatment and screening of maternal thyroid dysfunction.

Objectives: To study the current practices in the management of subclinical hypothyroidism (SCH) and thyroid nodules during pregnancy of obstetricians/gynecologists (OB/GYNs) and endocrinologists in Israel.

Methods: An electronic questionnaire was sent by email to all members of the Israeli Endocrine Society and the Israel Society of Obstetrics and Gynecology. Questionnaires included demographic data and clinical scenarios with questions regarding the screening and management of pregnant women with SCH, hypothyroxinemia, and a palpable thyroid nodule. The questionnaire for OB/GYNs was slightly modified.

Results: We received 90 responses from endocrinologists and 42 responses from OB/GYNs. Among endocrinologists, 39% would repeat a thyroid-stimulating hormone (TSH) test of 2.9 mU/L with normal free thyroxine and treat with thyroxine if the second result was above 2.5 mU/L. Among OB/GYNs, 73% would manage a woman with SCH at the beginning of her pregnancy by themselves and only 22% would start thyroxine after a first TSH result above 2.5 mU/L. Concerning screening, 57% endocrinologists and 71% OB/GYNs recommended screening for thyroid dysfunction in every woman at the beginning of her pregnancy. Among endocrinologists, 54% would order an ultrasound for a palpable thyroid nodule and perform a fine needle aspiration only for suspicious lesions.

Conclusions: The medical approach to thyroid disease in pregnant women remains a matter of controversy. Our results support the need for larger and prospective clinical studies.

Background: Survival of patients who were discharged from the hospital following out-of-hospital cardiac arrest (OHCA) has not been well defined.

Objective: To verify predictor variables for prognosis of patients following OHCA who survived hospitalization.

Methods: We retrospectively reviewed clinical, demographic, and outcome data of consecutive patients who were hospitalized from January 1, 2009, through December 31, 2014, into the intensive coronary care unit (ICCU) after aborted OHCA and discharged alive. The patients were followed until December 31, 2015.

Results: Of the 180 patients who were admitted into ICCU after OHCA, 64 were discharged alive (59.3%): 55 were male (85.9%), 14 died 16.5 ± 18 months after their discharge. During 1 year follow-up, nine patients (14.1%) died after a median period of 5.5 months and 55 patients (85.9 %) survived. Diabetes mellitus and chronic renal failure (CRF) were more frequent in patients who died within 1 year after their hospital discharge than those who survived. Ventricular fibrillation, such as initial arrhythmia, and opening of occluded infarct related artery were more frequent in survivors.

Conclusions: Most of the patients who were discharged after OHCA were alive at the 1 year follow-up. The risk of death of cardiac arrest survivors is greatest during the first year after discharge. CRF remains a poor long-term prognostic factor beyond the patients' discharge. Ventricular fibrillation, as initial arrhythmia, and opening of occluded infarct related artery have a positive impact on long-term survival.

Background: Bone maturation is currently assessed by subjective and automated radiography. 

Objectives: To evaluate the concordance and reproducibility of a quantitative ultrasound (QUS) based device versus X-ray based methods.

Methods: The study population comprised 150 children, 76 males, 4–17 years of age. X-ray scans were evaluated according to wrist, carpal and phalanx areas for bone age. QUS was performed by the the BAUS™ device (SonicBone, Rishon Lezion, Israel), using speed-of-sound (SOS) and distance attenuation factor (ATN) in similar areas. Data from 100 subjects were used to establish the device conversion equation, and 50 measurements were assigned to assess inter-modality agreement. 

Results: BAUS showed high repeatability performance, 0.73% relative standard deviation for SOS and 3.5% for ATN. R2 for the conversion equation, including gender, SOS, and ATN, was 0.80 for all methods (P < 0.001). There was no significant bias in bone age assessments.

Conclusions: Bone age assessment by SonicBone is comparable to the assessment by X-ray based methods. 

 

Background: Concerns about metformin-associated lactic acidosis (MALA) prohibit the use of metformin in a large subset of diabetic patients, mostly in patients with chronic kidney disease. Increasing evidence suggests that the current safety regulations may be overly restrictive.

Objectives: To examine the association between chronic metformin treatment and lactate level in acute illness on the first day of admission to an internal medicine ward.

Methods: We compared diabetic and non-diabetic hospitalized patients treated or not treated with metformin in different sets of kidney function.

Results: A total of 140 patients participated in the study, 54 diabetic patients on chronic metformin treatment, 33 diabetic patients without metformin and 53 patients with no diabetes. Most participants were admitted for conditions that prohibit metformin use, such as heart failure, hypoxia and sepsis. Average lactate level was significantly higher in the diabetes + metformin group compared to the diabetes non-metformin group. Metformin treatment was not associated with higher than normal lactate level (hyperlactatemia) or low pH. No patient was hospitalized for lactic acidosis as the main diagnosis.

Conclusions: Chronic metformin treatment mildly increases lactate level, but does not induce hyperlactatemia or lactic acidosis in acute illness on the first day of admission to an internal medicine ward. These data support the expansion of metformin use.