Are sodium-glucose co-transporter-2 inhibitors associated with improved outcomes in diabetic patients admitted to intensive care units with septic shock?

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been shown to reduce organ dysfunction in renal and cardiovascular disease. There are limited data on the role of SGLT2i in acute organ dysfunction. We conducted a study to assess the effect of SGLT2i taken prior to intensive care unit (ICU) admission in diabetic patients admitted with septic shock. METHODS: This retrospective cohort study used electronic medical records and included diabetic patients admitted to the ICU with septic shock. We compared diabetic patients on SGLT2i to those who were not on SGLT2i prior to admission. The primary outcome was in-hospital mortality, and secondary outcomes included hospital and ICU length of stay, use of renal replacement therapy, and 28- and 90-day mortality. RESULTS: A total of 98 diabetic patients was included in the study, 36 in the SGLT2i group and 62 in the non-SGLT2i group. The Sequential Organ Failure Assessment and Acute Physiology and Chronic Health Evaluation III scores were similar in the groups. Inpatient mortality was significantly lower in the SGLT2i group (5.6% vs. 27.4%, P=0.008). There was no significant difference in secondary outcomes. CONCLUSIONS: Our study found that diabetic patients on SGLT2i prior to hospitalization who were admitted to the ICU with septic shock had lower inpatient mortality compared to patients not on SGLT2i.

Intrafamilial and interfamilial heterogeneity of PINK1-associated Parkinson's disease in Sudan.

PINK1 is the second most predominant gene associated with autosomal recessive Parkinson's disease. Homozygous mutations in this gene are associated with an early onset of symptoms. Bradykinesia, tremors, and rigidity are common features, while dystonia, motor fluctuation, and non-motor symptoms occur in a lower percentage of cases and usually respond well to levodopa. We investigated 14 individuals with parkinsonism and eleven symptom-free siblings from three consanguineous Sudanese families, two of them multigenerational, using a custom gene panel screening 34 genes, 27 risk variants, and 8 candidate genes associated with parkinsonism. We found a known pathogenic nonsense PINK1 variant (NM_032409.3:c.1366C>T; p.(Gln456*)), a novel pathogenic single base duplication (NM_032409.3:c.1597dup; p.(Gln533Profs*29)), and another novel pathogenic insertion (NM_032409.3:c.1448_1449ins[1429_1443; TTGAG]; p.(Arg483Serfs*7)). All variants were homozygous and co-segregated in all affected family members. We also identified intrafamilial and interfamilial phenotypic heterogeneity associated with PINK1 mutations in these Sudanese cases, possibly reflecting the nature of the Sudanese population that has a large effective population size, which suggests a higher possibility of novel findings in monogenic and polygenic diseases in Sudan.

A Case Series of Spontaneous Pneumomediastinum With/Without Pneumothorax in COVID-19.

With the previous worldwide initial coronavirus disease 2019 (COVID-19) pandemic, a notable rise in spontaneous pneumomediastinum with/without pneumothorax (SPP) has been noted. Most cases were initially reported as complications secondary to barotrauma from mechanical ventilation (MV) with COVID-19. However, with the Delta strain, starting from December 2020, there have been multiple reports of SPP. The SPP is an uncommon complication outside use of assisted ventilation with either noninvasive positive pressure ventilation (NIPPV) or MV. COVID-19 has been linked to higher incidence of SPP without use of NIPPV or MV. We present a series of 5 cases with a polymerase chain reaction-confirmed COVID-19 diagnostic testing whose hospital course was complicated by SPP unrelated to the use of either NIPPV or MV.

Delayed Diagnosis of West Nile Meningoencephalitis in a Patient Receiving Rituximab for Rheumatoid Arthritis.

West Nile virus (WNV) neuroinvasive disease is associated with substantial morbidity and mortality. Clinical suspicion is usually confirmed with cerebrospinal (CSF) immunoglobulin M (IgM) detection using enzyme-linked immunoassay (ELISA) techniques. CSF polymerase chain reaction (PCR) is rarely used to confirm the disease and is not widely available. We present a detailed report of false-negative WNV IgM in a patient receiving rituximab therapy for rheumatoid arthritis. She was exposed to the virus during peak immunosuppression and strong clinical suspicion was confirmed with WNV PCR, illustrating the importance of such consideration with the recent incremental use of rituximab therapy. Despite the lack of specific anti-viral treatment for WNV, delayed consideration and diagnosis of WNV in those who are immunosuppressed would expose them to a wide panel of testing, with a subsequent increase in the cost of medical care.

Susac Syndrome Presenting as Recurrent Strokes.

Susac syndrome (SS) is a rare clinical entity that affects primarily young women and might result in significant morbidity. The triad that leads to suspecting the disease has classically been involvement of the brain, retina and inner ear. The likely pathology of the disease is thought to be immune mediated endotheliopathy; given its clinical and, possibly, pathological remission with immunosuppressive therapy. Here we describe an uncommon recurrent stroke in a young female that unfolds to Susac syndrome at the end. We also reviewed the literature behind diagnosis and treatment. Delayed diagnosis is associated with worse morbidity and mortality, and the most important predictor of long-term prognosis in the reported cases is the time to diagnosis. Therapies tried (with variable success) include corticosteroids, IVIG, plasmapheresis, cyclophosphamide, mycophenolate mofetil, and rituximab. The prognosis of SS is difficult to predict given the absence of strong clinical or radiographic features to suggest better/worse prognosis at the time of initial diagnosis. Brain MRIs and hearing/vision impairment have never normalized in previously studied cohort of patients.

Methylation of alpha-synuclein in a Sudanese cohort.

BACKGROUND: Several studies suggested a significant role of epigenetic changes, including alterations in miRNA, histone modifications, and DNA methylation of α-synuclein (SNCA) in Parkinson's disease (PD) pathogenicity. As of yet, only very few studies have been carried out in this field in Africa and none in Sudan. MATERIALS AND METHODS: We collected DNA from 172 Sudanese individuals (90 cases, 82 controls) who donated saliva for DNA extraction (mean age of onset: 40.6 ± 22.4 years). A family history of PD was evident in 64 patients. DNA preparation and bisulfite sequencing of SNCAintron1 was performed as described earlier. RESULTS: Of the fourteen analyzed CpGs of SNCAintron1, CpGs 16-23 were hypomethylated in PD (P-value ranged from 0.023 to 0.003). P-values improved, when sporadic cases were excluded from the analysis. CONCLUSION: We identified the presence of a specific pattern of DNA methylation in a young Sudanese cohort of familial PD, which confirms the importance of the methylation of SNCAintron1 for PD. This phenomenon appears to be independent of ethnicity, the impact of environmental factors, drug history, or familial clustering.

Yersinia enterocolitica Prosthetic Joint Septic Arthritis Successfully Treated with Ceftriaxone.

Yersinia enterocolitica is a Gram-negative coccobacillus that is known to cause gastroenteritis and symptoms mimicking appendicitis or terminal ileitis. It is also one of the culprit infections implicated in causing reactive arthritis. Rarely, it can cause musculoskeletal infections including osteomyelitis, septic arthritis, and discitis. We describe the case of a 70-year-old female with multiple comorbidities who presented with left knee pain and swelling after recent gastroenteritis. She was found to have Yersinia enterocolitica septic arthritis in her left knee prosthetic joint. The patient underwent an exchange of her prosthetic material and was successfully treated with a six-week course of ceftriaxone. Our article aims to highlight a rare manifestation of Yersinia enterocolitica infection and to point out an important differential for reactive arthritis after Yersinia enterocolitica infection.

Yellow Nail Syndrome: A Case Presentation and a Review of Management Options.

Yellow nail syndrome (YNS) has traditionally been thought of as a triad of exudative pleural effusion, yellow nails, and lymphedema. More recently, in addition to the hallmark yellowish nail discoloration, the diagnostic criteria required an associated lymphedema and/or chronic respiratory manifestations including pleural effusions, bronchiectasis or chronic sinusitis. Etiology remains unknown and treatment is supportive and directed towards patient's specific complaints. While described alongside multiple endocrine, lymphatic and autoimmune disorders, its most ominous association is malignancy, raising YNS as a possible paraneoplastic condition. Here we present the case of an 80 years-old female with worsening restrictive airway disease and acquired yellow nails, with development of dyspnea, cough and leg edema. Recurrent exudative lymphocyte predominant pleural effusion was treated definitively with pleurodesis. Her leg edema and yellow nails were treated conservatively. We describe previous case reports and series in the literature, outline therapeutic options and discuss prognosis.

Recurrent Lymphocytic Pleural Effusion as a Complication of Ventriculopleural Shunt Meningitis Caused by Cutibacterium Acnes.

Cutibacterium acnes (C. acnes) is part of the normal flora and has been linked to many invasive and pleural infections. Though it is usually considered a contaminant bacterium, full antimicrobial therapy might result in the resolution of foreign body-related infections. In this report, we describe an infection that started as ventriculopleural shunt meningitis but was complicated by a recurrent lymphocytic pleural infection. Ultimately, there was a resolution of pleural effusions after treatment of C. acnes.

Visual Disturbances in a Grave's Disease Patient After Sleeve Gastrectomy.

Wernicke encephalopathy (WE) is a neuropsychiatric disorder that results from untreated severe thiamine deficiency, frequently described as a triad of ophthalmoplegia, ataxia, and confusion. While this triad is commonly used to describe WE, all three symptoms are observed in less than 20 percent of individuals with this diagnosis. Most commonly, WE is observed in individuals with significant alcohol use and associated malnutrition resulting in thiamine deficiency. However, this condition can also be diagnosed in patients with other sources of malnutrition, and less frequently in hypermetabolic states such as those with hyperthyroidism. Due to its broad clinical presentation and numerous causes, Wernicke encephalopathy can be difficult to diagnose. Diagnosis of WE guides management, as glucose before IV thiamine administration can be detrimental. Therefore, it is essential to understand the complexities of WE. In this paper, we discuss a patient who presented to the emergency department complaining of central vision loss, change in color perception, tinnitus, and difficulty walking two months post gastric sleeve and a recently diagnosed and, possibly inadequately treated, hyperthyroidism. The combination of recent sleeve gastrectomy and hyperthyroidism likely led to thiamine malabsorption and hypermetabolism, resulting in WE.

Comparative accuracy of non-invasive imaging versus right heart catheterization for the diagnosis of pulmonary hypertension: A systematic review and meta-analysis.

BACKGROUND: Right heart catheterization (RHC) is the gold-standard in the diagnosis of pulmonary hypertension (PH) but at the cost of procedure-related complications. We sought to determine the comparative accuracy of RHC versus non-invasive imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI), and transthoracic echocardiography (TTE). METHODS: Pulmonary hypertension was defined as a mean pulmonary artery pressure (mPAP) of>20 mmHg. Multiple databases were queried for relevant articles. Raw data were pooled using a bivariate model to calculate the measures of diagnostic accuracy and to estimate Hierarchical Summary Receiver Operating Characteristic (HSROC) on Stata 13. RESULTS: A total of 51 studies with a total patient population of 3947 were selected. The pooled sensitivity and specificity of MRI for diagnosing PH was 0.92(95% confidence interval (CI) 0.88-0.96) and 0.86 (95% CI, 0.77-0.95), respectively. The net sensitivities for CT scan and TTE were 0.79 (95% CI 0.72-0.89) and 0.85 (95% CI 0.83-0.91), respectively. The overall specificity was 0.82 (0.76-0.92) for the CT scan and 0.71 (95% CI 0.61-0.84) for TTE. The diagnostic odds ratio (DOR) for MRI was 124 (95% CI 36-433) compared to 30 (95% CI 11-78) and 24 (95% 11-38) for CT scan and TTE, respectively. Chi-squared (x2) test showed moderate heterogeneity on the test for equality of sensitivities and specificities. CONCLUSIONS: MRI has the highest sensitivity and specificity compared to CT and TTE. MRI can potentially serve as a surrogate technique to RHC for the diagnosis of PH.

Severe Neutropenia Complicated with Necrotizing Fasciitis Unveils a Diagnosis of Rheumatoid Arthritis: A Case Report.

Felty syndrome, a rare extra-articular manifestation of rheumatoid arthritis (RA), usually affects patients with long-standing disease. Patients with this syndrome typically present with neutropenia, splenomegaly, in addition to erosive RA. The development of unexplained neutropenia in healthy patients should prompt the work up for Felty syndrome, especially in patients with suggestive demographics, signs, and symptoms. Differentiation between large granular lymphocyte (LGL) leukemia and Felty syndrome is necessary as both can present with neutropenia, and are associated with RA. Immunosuppressive therapy has improved the prognosis of patients with Felty syndrome given the decreasing rates of splenectomies done in those patients over the last decades.

Breaking bad news from the doctors' perspective in a paternalistic society: the case of Sudan.

Breaking bad news is a global challenge for all types of health providers. Our study assessed the attitude and practice from the doctors' perspective in a patriarchal society. A descriptive cross-sectional hospital-based study was conducted, involving doctors from both medical and surgical departments. Almost half of the respondents believed that Sudanese patients do not like to know their diagnosis, and a slightly higher proportion had no previous training on how to break bad news. Some 20% indicated that they would conceal the diagnosis from a patient if his or her relatives so requested. Less than one-quarter of respondents followed a standard protocol. Although most of the doctors subscribed to the notion that patients have the right to know everything about their illnesses, not all of them held this attitude towards their local patient population.

Monoallelic characteristic-bearing heterozygous L1053X in BRCA2 gene among Sudanese women with breast cancer.

BACKGROUND: Breast cancer (BC) is the most common type of cancer in women. Among many risk factors of BC, mutations in BRCA2 gene were found to be the primary cause in 5-10% of cases. The majority of deleterious mutations are frameshift or nonsense mutations. Most of the reported BRCA2 mutations are protein truncating mutations. METHODS: The study aimed to describe the pattern of mutations including single nucleotide polymorphisms (SNPs) and variants of the BRCA2 (exon11) gene among Sudanese women patients diagnosed with BC. In this study a specific region of BRCA2 exon 11 was targeted using PCR and DNA sequencing. RESULTS: Early onset cases 25/45 (55.6%) were premenopausal women with a mean age of 36.6 years. Multiparity was more frequent within the study amounting to 30 cases (66.6%), with a mean parity of 4.1. Ductal type tumor was the predominant type detected in 22 cases (48.8%) among the reported histotypes. A heterozygous monoallelic nonsense mutation at nucleotide 3385 was found in four patients out of 9, where TTA codon was converted into the stop codon TGA. CONCLUSION: This study detected a monoallelic nonsense mutation in four Sudanese female patients diagnosed with early onset BC from different families. Further work is needed to demonstrate its usefulness in screening of BC.

Multiplicity of infection and genetic diversity of Plasmodium falciparum isolates from patients with uncomplicated and severe malaria in Gezira State, Sudan.

BACKGROUND: Multiplicity and genetic diversity of Plasmodium falciparum infection might play a role in determining the clinical outcome of malaria infection and could be a fair reflection of the disease transmission rate. This study investigated the genetic diversity of P. falciparum and multiplicity of infection in relation to the severity of malaria and age of patients in Gezira State, Sudan. METHODS: A cross-sectional health facilities-based survey was conducted in Gezira State, Sudan in January 2012. A total of 140 P. falciparum malaria patients diagnosed with microscopy and confirmed using nested PCR were recruited and classified into uncomplicated malaria and severe malaria states according to the standard WHO criteria. DNA was extracted and MSP1 and MSP2 allelic families were determined using nested PCR. RESULTS: The overall multiplicity of infection (MOI) was 2.25 and 2.30 and 2.15 for uncomplicated and severe malaria respectively. There were no statistically significant differences between uncomplicated and severe malaria (SM) patient groups in MOI with regard to MSP1, MSP2 and overall MOI (Mann-Whitney U-test; all P < 0.05). The predominant MSP1 allelic families were MAD20 for uncomplicated malaria and RO33 for severe malaria. The distribution of both FC27 and IC1/3D7 MSP2 allelic families were approximately the same across disease severity. One hundred and eleven P. falciparum isolates (81 %) consisted of multiple genotypes; 71/90 (78.9 %) in uncomplicated malaria and 40/50 (85.1 %) in severe malaria patient groups. Neither MSP1 nor MSP2 allelic families showed association with malaria severity. No statistically significant differences in multiplicity of infection were observed between different age groups. CONCLUSION: In this study the majority of P. falciparum isolates from uncomplicated and severe malaria patients consisted of multiple genotypes. Further molecular epidemiological studies delineate the link between P. falciparum genotype with the malaria phenotype in different regions are encouraged.