Prospective Newborn Screening for SCID in Germany: A First Analysis by the Pediatric Immunology Working Group (API)

Background: T-cell receptor excision circle (TREC)-based newborn screening (NBS) for severe combined immunodeficiencies (SCID) was introduced in Germany in August 2019. / Methods: Children with abnormal TREC-NBS were referred to a newly established network of Combined Immunodeficiency (CID) Clinics and Centers. The Working Group for Pediatric Immunology (API) and German Society for Newborn Screening (DGNS) performed 6-monthly surveys to assess the TREC-NBS process after 2.5 years. / Results: Among 1.9 million screened newborns, 88 patients with congenital T-cell lymphocytopenia were identified (25 SCID, 17 leaky SCID/Omenn syndrome (OS)/idiopathic T-cell lymphocytopenia, and 46 syndromic disorders). A genetic diagnosis was established in 88%. Twenty-six patients underwent hematopoietic stem cell transplantation (HSCT), 23/26 within 4 months of life. Of these, 25/26 (96%) were alive at last follow-up. Two patients presented with in utero onset OS and died after birth. Five patients with syndromic disorders underwent thymus transplantation. Eight syndromic patients deceased, all from non-immunological complications. TREC-NBS missed one patient, who later presented clinically, and one tracking failure occurred after an inconclusive screening result. / Conclusion: The German TREC-NBS represents the largest European SCID screening at this point. The incidence of SCID/leaky SCID/OS in Germany is approximately 1:54,000, very similar to previous observations from North American and European regions and countries where TREC-NBS was implemented. The newly founded API-CID network facilitates tracking and treatment of identified patients. Short-term HSCT outcome was excellent, but NBS and transplant registries will remain essential to evaluate the long-term outcome and to compare results across the rising numbers of TREC-NBS programs across Europe

The charcot foot in diabetes.

The diabetic Charcot foot syndrome is a serious and potentially limb-threatening lower-extremity complication of diabetes. First described in 1883, this enigmatic condition continues to challenge even the most experienced practitioners. Now considered an inflammatory syndrome, the diabetic Charcot foot is characterized by varying degrees of bone and joint disorganization secondary to underlying neuropathy, trauma, and perturbations of bone metabolism. An international task force of experts was convened by the American Diabetes Association and the American Podiatric Medical Association in January 2011 to summarize available evidence on the pathophysiology, natural history, presentations, and treatment recommendations for this entity

P67-phox (NCF2) Lacking Exons 11 and 12 Is Functionally Active and Leads to an Extremely Late Diagnosis of Chronic Granulomatous Disease (CGD)

Two brothers in their fifties presented with a medical history of suspected fungal allergy, allergic bronchopulmonary aspergillosis, alveolitis, and invasive aspergillosis and pulmonary fistula, respectively. Eventually, after a delay of 50 years, chronic granulomatous disease (CGD) was diagnosed in the index patient. We found a new splice mutation in the NCF2 (p67-phox) gene, c.1000+2T→G, that led to several splice products one of which lacked exons 11 and 12. This deletion was in frame and allowed for remarkable residual NADPH oxidase activity as determined by transduction experiments using a retroviral vector. We conclude that p67-phox which lacks the 34 amino acids encoded by the two exons can still exert considerable functional activity. This activity can partially explain the long-term survival of the patients without adequate diagnosis and treatment, but could not prevent progressing lung damage

Surgical management of Diabetic foot ulcers: A Tanzanian university teaching hospital experience

\ud \ud Diabetic foot ulcers (DFUs) pose a therapeutic challenge to surgeons, especially in developing countries where health care resources are limited and the vast majority of patients present to health facilities late with advanced foot ulcers. A prospective descriptive study was done at Bugando Medical Centre from February 2008 to January 2010 to describe our experience in the surgical management of DFUs in our local environment and compare with what is known in the literature. Of the total 4238 diabetic patients seen at BMC during the period under study, 136 (3.2%) patients had DFUs. Males outnumbered females by the ratio of 1.2:1. Their mean age was 54.32 years (ranged 21-72years). Thirty-eight (27.9%) patients were newly diagnosed diabetic patients. The majority of patients (95.5%) had type 2 diabetes mellitus. The mean duration of diabetes was 8.2 years while the duration of DFUs was 18.34 weeks. Fourteen (10.3%) patients had previous history of foot ulcers and six (4.4%) patients had previous amputations. The forefoot was commonly affected in 60.3% of cases. Neuropathic ulcers were the most common type of DFUs in 57.4% of cases. Wagner's stage 4 and 5 ulcers were the most prevalent at 29.4% and 23.5% respectively. The majority of patients (72.1%) were treated surgically. Lower limb amputation was the most common surgical procedure performed in 56.7% of cases. The complication rate was (33.5%) and surgical site infection was the most common complication (18.8%). Bacterial profile revealed polymicrobial pattern and Staphylococcus aureus was the most frequent microorganism isolated. All the microorganisms isolated showed high resistance to commonly used antibiotics except for Meropenem and imipenem, which were 100% sensitive each respectively. The mean hospital stay was 36.24 ± 12.62 days (ranged 18-128 days). Mortality rate was 13.2%. Diabetic foot ulceration constitutes a major source of morbidity and mortality among patients with diabetes mellitus at Bugando Medical Centre and is the leading cause of non-traumatic lower limb amputation. A multidisciplinary team approach targeting at good glycaemic control, education on foot care and appropriate footware, control of infection and early surgical intervention is required in order to reduce the morbidity and mortality associated with DFUs. Due to polymicrobial infection and antibiotic resistance, surgical intervention must be concerned

Pentanol isomer synthesis in engineered microorganisms

Pentanol isomers such as 2-methyl-1-butanol and 3-methyl-1-butanol are a useful class of chemicals with a potential application as biofuels. They are found as natural by-products of microbial fermentations from amino acid substrates. However, the production titer and yield of the natural processes are too low to be considered for practical applications. Through metabolic engineering, microbial strains for the production of these isomers have been developed, as well as that for 1-pentanol and pentenol. Although the current production levels are still too low for immediate industrial applications, the approach holds significant promise for major breakthroughs in production efficiency

Fast, Multiphase Volume Adaptation to Hyperosmotic Shock by Escherichia coli

All living cells employ an array of different mechanisms to help them survive changes in extra cellular osmotic pressure. The difference in the concentration of chemicals in a bacterium's cytoplasm and the external environment generates an osmotic pressure that inflates the cell. It is thought that the bacterium Escherichia coli use a number of interconnected systems to adapt to changes in external pressure, allowing them to maintain turgor and live in surroundings that range more than two-hundred-fold in external osmolality. Here, we use fluorescence imaging to make the first measurements of cell volume changes over time during hyperosmotic shock and subsequent adaptation on a single cell level in vivo with a time resolution on the order of seconds. We directly observe two previously unseen phases of the cytoplasmic water efflux upon hyperosmotic shock. Furthermore, we monitor cell volume changes during the post-shock recovery and observe a two-phase response that depends on the shock magnitude. The initial phase of recovery is fast, on the order of 15–20 min and shows little cell-to-cell variation. For large sucrose shocks, a secondary phase that lasts several hours adds to the recovery. We find that cells are able to recover fully from shocks as high as 1 Osmol/kg using existing systems, but that for larger shocks, protein synthesis is required for full recovery