Volume Articles

Pulmonary Alveolar Proteinosis: Own Experience of Diagnosis and Treatment

Boris M. Ariel^1,2*, Ivetta V. Dvorakovskaya^1,3, Ludmila N. Novikova³, Mikhail M. Ilkovich³

¹St. Petersburg Research Institute of Phthisiopulmonology, Health Ministry of Russia, St. Petersburg, Russia

²St. Petersburg City Mortem Bureau, St. Petersburg, Russia

³Pulmonology Clinic of Pavlov State Medical University, St. Petersburg, Russia

Pulmonary alveolar proteinosis (PAP) is a rare interstitial lung disease with severe impairment of respiratory function caused by some genetic abnormalities of surfactant production and utilization. One of the clue moments in the pathogenesis of this disease which can lead to respiratory failure and death is the pulmonary fibrosis development occurring occasionally in patients with moderate and severe PAP. According to our own experience in 1977-2018 whole and segmental lung lavage remains the first-line treatment of PAP; 70 patients (82%) had shown an improvement after this treatment. A noticeable improvement was achieved in 67 patients (79%), and no serious complications were observed. The 5-year survival rate reached 100%. Nevertheless, delayed diagnosis and incorrect administration of antibiotics and tuberculostatics reduce the probability of a long symptom-free period after lung lavage and resolution of the disease.

Metastatic Carcinoma to the Testis - A Mini Review

Gang Wang*

Department of Pathology, BC Cancer Vancouver Centre, University of British Columbia, Vancouver, BC, Canada

Metastatic carcinomas to the testis are extremely rare and have been reported only in autopsy series or case reports. However, when they occur, the metastatic tumors in the testis are usually unilateral and solitary, may have overlap growth patterns and cytological features with primary testicular tumors, including those of rete/epididymis origin, mesothelial origin and Sertoli cell tumor. It will make the diagnosis very challenging, especially when there is no known history of a primary tumor in other sites. Metastatic prostatic adenocarcinoma counts nearly half of the overall metastatic carcinoma in the testis, followed by colorectal carcinoma and renal cell carcinoma. Here, we review our experience and summarize the reported cases from the literature, to emphasize some of the unusual aspects of metastatic carcinoma to the testis, and discuss the main differential diagnoses for this rare condition. Awareness of the features of these tumors, consideration of the possibility of metastasis and appropriate ancillary studies are the keys to the accurate diagnosis of these cases.

Robust Sampling of Altered Pathways for Drug Repositioning Reveals Promising Novel Therapeutics for Inclusion Body Myositis

Juan Luis Fernández-Martínez*, Oscar Álvarez, Enrique J. DeAndrés-Galiana, Javier Fernández-Sánchez de la Viña, Leticia Huergo

Group of Inverse Problems, Optimization and Machine Learning. Department of Mathematics. University of Oviedo, Oviedo, 33007, Asturias, Spain.

In this paper we present a robust methodology to deal with phenotype prediction problems associated to drug repositioning in rare diseases, which is based on the robust sampling of altered pathways. We show the application to the analysis of IBM (Inclusion Body Myositis) providing new insights about the mechanisms involved in its development: cytotoxic CD8 T cell-mediated immune response and pathogenic protein accumulation in myofibrils related to the proteasome inhibition. The originality of this methodology consists of performing a robust and deep sampling of the altered pathways and relating these results to possible compounds via the connectivity map paradigm. The methodology is particularly well-suited for the case of rare diseases where few genetic samples are at disposal. We believe that this method for drug optimization is more effective and complementary to the target centric approach that loses efficacy due to a poor understanding of the disease mechanisms to establish an optimum mechanism of action (MoA) in the designed drugs. However, the efficacy of the list of drugs and gene targets provided by this approach should be preclinically validated and clinically tested. This methodology can be easily adapted to other rare and non-rare diseases.

A Commentary on "A Novel Imaging Finding in Williams Syndrome: The Coral Sign"

Ali M Agha¹, Jeremy Burt²*

¹The McGovern Medical School at UT Houston, Department of Internal Medicine, USA

²AdventHealth Orlando, Department of Radiology, USA

Identification of a novel MTTP splice variant c.394-2A>C in an infant with abetalipoproteinemia

Dinesha M. Vidanapathirana^1,2*, Eresha Jasinge¹, Samantha Waidyanatha³, Amanda J. Hooper^4,5, John R. Burnett^4,5

¹Department of Chemical Pathology, Lady Ridgeway Hospital for Children, Sri Lanka

²Department of Pathology, Faculty of Medical Sciences, University of Sri Jayewardenepura, Sri Lanka

³Department of Paediatrics, Lady Ridgeway Hospital, Sri Lanka

⁴Department of Clinical Biochemistry, PathWest Laboratory Medicine, Royal Perth Hospital and Fiona Stanley Hospital Network, Perth, Australia

⁵School of Medicine, University of Western Australia, Australia

Abetalipoproteinemia (ABL) is a rare autosomal recessive disorder of lipoprotein metabolism caused by mutations in the microsomal triglyceride transfer protein (MTTP) gene. To date, less than 100 cases of ABL have been reported worldwide. It is characterized biochemically by the absence or extremely low levels of low-density lipoproteins in the blood. We report a four-month-old girl, born to consanguineous parents, who presented with steatorrhea, failure to thrive, marked hypolipidemia and acanthocytosis, with a similar history having been noted in her older sibling. DNA sequencing revealed the infant to be homozygous for a novel pathogenic MTTP splice variant c.394-2A?C. Family screening revealed her sister to be homozygous for the same MTTP variant while her parents were heterozygotes. Early diagnosis and treatment of ABL in the form of a low-fat diet and fat-soluble vitamin supplementation can mitigate neuropathy and retinopathy. We believe that this is the first identification of an infant with a novel mutation for abetalipoproteinemia in Sri Lanka.

Multiple Exostosis Disease

Moustapha Niasse¹*, Baïdy Sy Kane², Kaba Condé³, Silly Touré⁴, Lamine Sarr⁵, Coumba Diouf¹, Saïdou Diallo¹

¹Department of Rheumatology, University Hospital Aristide Le Dantec of Dakar, Senegal

²Department of Internal Medicine, University Hospital Aristide Le Dantec of Dakar, Senegal

³Department of Rheumatology, University Hospital Ignace Deen of Conakry, Guinea

⁴Department of Stomatology and Maxillofacial surgery, University Hospital Aristide Le Dantec of Dakar, Senegal

⁵Department of Orthopaedics and Traumatology, University Hospital Aristide Le Dantec of Dakar, Senegal

Multiple exostosis disease is one of the hereditary diseases with autosomal dominant transmission. It is characterized by the proliferation of bone protuberances, especially located in the metaphysis of long bones.

Since 1993, advances have been noted in knowledge of the pathophysiology of this disease, in particular with the discovery of the mutation of EXT genes, found in 80% of multiple exostosis disease. These genes, tumor suppressors, code for proteins involved in the synthesis of heparan sulfates. The deficiency in quantity and quality of heparan sulfates leads to changes in certain metabolic processes, which leads to the development of ectopic growth plaques. This is responsible for the development of exostosis, but also for the low longitudinal growth of long bones. The disease phenotype may also associate abnormalities in the shape and length of long bones, such as the typical “Bessel Hagen” deformity. Clinically, bone masses are often painless. The rare complication (2 to 5% of cases) but the most feared is the transformation into chondrosarcoma, which motivates regular clinical and radiological monitoring of these patients. Treatment, mainly surgical, is indicated in case of symptoms (pain, increased exostosis volume after the end of growth, compression of neighboring organs.

High Molecular Weight Hyaluronic Acid (Hyalubrix/HyalOne) for Treating Symptomatic Hip Osteoarthritis

Alberto Migliore¹*, Gianfranco Gigliucci¹, Sandro Tormenta², Angelo De Cata³, Luca Gallelli⁴, Giovanni Iolascon⁵

¹Rheumatology Unit and Research Center, S. Pietro Fatebenefratelli Hospital, Rome, Italy

²Radiology Unit, S. Pietro Fatebenefratelli Hospital, Rome, Italy

³Department of Medical Sciences, Division of Internal Medicine and Rheumatology Unit, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo (FG), Italy

⁴Chair of Pharmacology Department of Health Science, University of Catanzaro School of Medicine, and Operative Unit of Clinical Pharmacology and Pharmacovigilance, Azienda Ospedaliera MaterDomini, Catanzaro, Italy

⁵Department of Medical and Surgical Specialties and Dentistry, University of Campania "Luigi Vanvitelli", Naples, Italy

Hip osteoarthritis (OA) causes a set of symptoms that may lead to severe patient impairment, social isolation and morbidity, especially in the elderly. Eventually, patients become candidates for total hip replacement (THR); yet surgery may cause morbidity, increase costs and be too risky in some cases. Viscosupplementation (VS) by intra-articular hyaluronic acid (HA) injection has been shown to be effective to treat symptoms consequent to knee OA. VS is a viable option to treat hip OA too, provided that appropriate techniques are used to inject HA into the articular space. To this end, ultrasound-guided approaches have been developed that allow appropriate intra-articular injection eliminating the risk of exposure to ionizing radiation entailed by fluoroscopy. This review summarizes the results of clinical investigations concerning the use of a high molecular weight HA formulation, Hyalubrix/HyalOne, for treating hip OA symptoms. These results show that Hyalubrix/HyalOne has an enhanced safety profile, is effective from the first injection, significantly reduces NSAIDs consumption, and can be used for repeated therapy cycles over more years as a conservative therapy to delay THR. Nevertheless, it must be also considered that a significant placebo effect linked to intra-articular injections may exist, thus reducing the magnitude of HA benefits.