Israel Medical Association Journal

The patient, a 32-year-old woman diagnosed with Sjögren's syndrome (SS), according to the 2016 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria, presented with paresthesia of her face and limbs. Extra glandular manifestations of her primary disease included severe Raynaud's phenomenon and chronic interstitial nephritis. There was no family history of neurologic diseases. Neurological examination was notable for symmetrical decreased sensation in the upper limbs distally. The rest of the neurological examination was unremarkable.

Pancreaticopleural fistula (PPF) is a rare complication of pancreatitis and usually constitutes a diagnostic challenge. There are many causes for recurrent and chronic pancreatitis, with the main etiology being alcohol and choledocholithiasis [1]. However, the association between pancreatic divisum (PD), a common congenital anomaly of the pancreas that is rarely symptomatic, and complications of pancreatitis is still not firmly established [2]. Furthermore, the optimal management of PPF is still uncertain due to its rarity [3]. We describe a rare case of a 45-year-old woman with recurrent pancreatitis that presented with a PPF on the background of PD, successfully managed with conservative treatment. The purpose of this report is to highlight the rare association between PPF and PD together with the excellent response to conservative therapy.

Sulfonylureas have been used to treat patients with diabetes for the last 80 years. The main side effect of this drug class is hypoglycemia, which might be severe and protracted. With the emergence of new medications with improved safety and better efficacy in preventing diabetes complications and cardiovascular morbidity and mortality, the use of these agents is waning.

Sulfonylureas are historically classified into two generations. The generation first includes drugs such as tolbutamide and chlorpropamide, which are no longer used. The second generation includes glibenclamide and glimepiride, which have different pharmacokinetic properties and active metabolites.

In this case report, we present a patient with diabetes and end-stage renal disease (ESRD) who developed prolonged hypoglycemia following the unauthorized use of a food supplement containing the first-generation sulfonylurea - tolbutamide.

Carbamoyl phosphate synthetase 1 (CPS1; MIM *608307; E.C. 6.3.4.16) is the first rate-limiting enzyme of the urea cycle, an essential metabolic pathway for ammonia detoxification. CPS1 deficiency (CPS1-D) is characterized by severe hyperammonemia during disease exacerbations. During a metabolic crisis, children with CPS1-D are admitted with vomiting, altered mental status, and high serum levels of ammonia. Rapid normalization of ammonia level ameliorates neurological outcome [1,2]. The first-line treatment for hyperammonemia in these patients is ammonia scavengers in combination with citrulline or arginine and high-calorie supplementation while controlling protein intake [1].

In September 2020, a 37-year-old man without significant medical history or medication use presented to the emergency department with shortness of breath. The patient denied any history of shortness of breath, travel history, recent sick contacts, or history of lung disease. On arrival, the patient was afebrile with a respiratory rate of 26 breaths per minute (b/m), oxygen saturation 82% on ambient air, blood pressure 130\80 mmHg, and heart rate 130 beats per minute (bpm). He was started on three liters per minute oxygen therapy, which improved his saturation to 90%. Physical examination was remarkable for tachypnea and diffuse bilateral inspiratory lung crackles. Electrocardiogram revealed sinus tachycardia.

A 26-year-old female at 28 weeks of gestation with her fourth pregnancy presented with a 24-hour history of diffuse abdominal pain and distension. In addition, she had nausea, vomiting, and constipation. The pain did not respond to analgesics. She had poor prenatal care during her pregnancy. She had previously had three cesarean deliveries. The first cesarean delivery was due to non-progressive second stage of labor, the second was preterm due to abdominal pain and suspected uterine rupture, and the last was due to the previous cesarean deliveries. In her last previous pregnancy, she presented with recurrent milder abdominal pain, which resolved spontaneously.

On examination, she was afebrile, with normal blood pressure and heart rate. Her abdomen was distended, tympanic, and mildly tender to palpation with no tenderness on the cesarean scar and no peritoneal signs. Her laboratory testing was normal except for mild hypokalemia.

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.

Fetal hydrops is a life-threatening condition defined as abnormal accumulation of fluid in two or more fetal compartments: ascites, pleural effusion, pericardial effusion, or generalized skin edema [1]. Fetal hydrops may also be associated with polyhydramnios and placental edema [2].

Based on pathophysiology results, fetal hydrops is classified as either immune or non-immune. The frequency of immune fetal hydrops has decreased dramatically since the development of Rh (D) immunization given to mothers at risk. Nonimmune hydrops fetalis (NIHF) accounts for almost 90% of cases [1]. The etiology of NIHF is further classified as cardiovascular (17–35%), chromosomal (7–16%), hematologic (4–12%), infectious (5–7%), and unknown (15–25%). Inborn errors of metabolism account for only 1–2% of NIHF cases [1]. NIHF is commonly progressive. Complete resolution of NIHF before birth is rare.

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].

Gallbladder metastasis is an extremely rare entity [1]. It is mainly secondary to melanoma but has also been reported as originating from breast cancer, renal cell carcinoma, and gastric cancer. Its diagnosis is often late in the advanced stage of the disease with the involvement of other organ systems [2].

We present a case of a patient who developed gastric cancer gallbladder metastasis. These findings are usually incidental on pathology of cholecystectomy specimens [1]. In our case, the metastatic lesion was demonstrated on magnetic resonance imaging (MRI) prior to surgery. Of note, the lesion had a similar enhancement pattern to the primary tumor.

Global developmental delay (GDD), defined as a significant delay in two or more developmental domains (e.g., gross/fine motor, cognitive, speech/language, personal/social, activities of daily living), affects 1–3% of children. According to the Israeli Ministry of Health, thyroid function studies are not indicated in children with GDD unless there are systemic features suggestive of thyroid dysfunction (https://www.health.gov.il/hozer/mr36_2012.pdf). This approach also exists in other countries with newborn screening programs for congenital hypothyroidism.

We present the case of an infant with GDD, who despite normal newborn screening tests, underwent a repeated extended thyroid function analysis (including T₃ levels) leading to a diagnosis of Allan-Herndon-Dudley syndrome, a rare genetic neurodevelopmental syndrome.

Ruxolitinib is an inhibitor of the cytosolic tyrosine kinase Janus kinase (JAK) family of proteins (JAK1/2), which is widely used to treat various myeloid neoplasms that are characterized by constant activation of the JAK-STAT signaling pathway.

Many side effects are associated with ruxolitinib, including anemia, thrombocytopenia, increased rate of infections (especially herpes zoster), and mild hypercalcemia noted in 15.4% of patients [1]. The possible mechanism causing hypercalcemia may involve altered bone and mineral metabolism with secondary hyperparathyroidism, as described for other kinase inhibitors [2].

Familial spastic paraparesis is a non-progressive disorder. However, clinical experience shows that after trauma, disease, surgery, or limb fracture that force a patient's long immobilization, a significant functional deterioration is observed. I describe two patients with Silver syndrome who experienced such functional deterioration after sustaining a simple fracture. A description of Silver syndrome and a biographical sketch of Dr. Silver, who explained the disorder in 1966, are given.

Romidepsin is an intravenously administered antineoplastic agent, which acts by inhibiting histone deacetylases, thus preventing removal of acetyl groups from histones. The accrual of acetyl groups on histones causes cell cycle arrest and apoptotic cell death. It was approved for use in the United States in 2009 for treatment of refractory or relapsed cutaneous and peripheral T cell lymphomas [1-3].

The most common side effects are mild to moderate in severity and include nausea, vomiting, fatigue, fever, myelosuppression (e.g., anemia, neutropenia, thrombocytopenia), elevated liver enzymes, constipation, and rash. More severe adverse events can include marked neutropenia, thrombocytopenia, serious infections such as line sepsis, acute renal failure, tumor lysis syndrome, and cardiac arrhythmias [1].

The health of survivors of the Shoah has been investigated, both at early and late stages in their lives. There have been findings of multiple morbidities, but survivors have enjoyed slightly prolonged longevity when compared to the general population [1]. Less attention has been granted to investigations and descriptions of illnesses that presented inside the ghettos and the Nazi camps. Some of the surviving records from those sites have yet to be interpreted. Documented diagnoses of both insulin dependent and mature onset diabetes mellitus and of malignancy has been conspicuously absent. We present our meta-analysis and interpretations of surviving medical documents covering a large population of prisoners from a range of ghettos and concentration camps and specifically note the absence of recorded incidence of malignancy and a relatively low incidence of diabetes mellitus.