Mild Clinical Presentation Research Articles

A multidisciplinary telemedicine model for management of coronavirus disease 2019 (COVID-19) in obstetrical patients

BackgroundThe COVID-19 pandemic caused by the SARS-CoV-2 has increased the demand for inpatient healthcare resources; however, approximately 80% of patients with COVID-19 have a mild clinical presentation and can be managed at home.ObjectiveThis study aimed to describe the feasibility and clinical and process outcomes associated with a multidisciplinary telemedicine surveillance model to triage and manage obstetrical patients with known exposures and symptoms of COVID-19.Study DesignWe implemented a multidisciplinary telemedicine surveillance model with obstetrical physicians and nurses to standardize ambulatory care for obstetrical patients with confirmed or suspected COVID-19 based on the symptoms or exposures at an urban academic tertiary care center with multiple hospital-affiliated and community-based practices. All pregnant or postpartum patients with COVID-19 symptoms, exposures, or hospitalization were eligible for inclusion in the program. Patients were assessed by means of regular nursing phone calls and were managed according to illness severity. Patient characteristics and clinical and process outcomes were abstracted from the electronic medical record.ResultsA total of 135 patients were enrolled in the multidisciplinary telemedicine model from March 17 to April 19, 2020, of whom 130 were pregnant and 5 were recently postpartum. In this study, 116 of 135 patients (86%) were managed solely in the outpatient setting and did not require an in-person evaluation; 9 patients were ultimately admitted after ambulatory or urgent evaluations, and 10 patients were observed after hospital discharge. Although only 50% of the patients were tested secondary to limitations in ambulatory testing, 1 in 3 of those patients received positive results for SARS-CoV-2 (N=22, 16% of entire cohort). Patients were enrolled in the telemedicine model for a median of 7 days (interquartile range, 4–8) and averaged 1 phone call daily, resulting in 891 nursing calls and 20 physician calls over 1 month.ConclusionA multidisciplinary telemedicine surveillance model for outpatient management of obstetrical patients with COVID-19 symptoms and exposures is feasible and resulted in rates of ambulatory management similar to those seen in nonpregnant patients. A centralized model for telemedicine surveillance of obstetrical patients with COVID-19 symptoms may preserve inpatient resources and prevent avoidable staff and patient exposures, particularly in centers with multiple ambulatory practice settings.

The c.3140-26A>G Variant of the CFTR Gene in Homozygous State Causes Mild Cystic Fibrosis – Overview of Longitudinal Clinical Data of the Patient Managed in our CF Center and Review of the Literature

There are over 70.000 patients with cystic fibrosis (CF) in the world and numerous sequence variations in the CFTR gene have been reported but the clinical significance of all of them is still not known. There are currently 195 patients with the c.3140-26A>G (legacy name 3272-26A>G) variant in the CFTR gene listed in the European Cystic Fibrosis Society Patient Registry (ECFSPR) and only 4 are homozygous. We present longitudinal clinical data of one of these patients who is managed in our CF Center at the University Children's Hospital in Ljubljana and compare it with the patient data from the ECFSPR and the CFTR2 database in which additional 3 homozygous patients are described. Moreover, the effect of the detected variant in the described patient was evaluated on the RNA level in nasal epithelial cells. The variant was shown to result in aberrant splicing introducing a frameshift and a premature termination codon while normal transcript was not detected. Alternative spliced mutant transcripts in other tissues or the presence of spliceosome-mediated RNA trans-splicing could explain the mild clinical presentation of patients with this variant in homozygous state.

Ten Years' Experiences in the Treatment of Nonaneurysmal Subarachnoid Hemorrhage: A Retrospective Analysis of Outcome Parameters in a Single-Center Study.

Objectives:Subarachnoid hemorrhage (SAH) with negative angiographic findings has a heterogeneous nature with variations in clinical course and outcome as compared to the aneurysmal SAH. It makes up to 15% of the spontaneous SAH and is characterized by milder clinical presentation. The purpose of this study was the analyses of risk factors, clinical observations, radiologic characteristics, and outcome in patients with nonaneurysmal SAH (NA-SAH).Patients and Methods:In a retrospective design, 77 consecutive patients with NA-SAH were recruited from May 2008, to October 2018. All patients underwent conventional cerebral angiography. We stratified patients into two groups based on the distribution of blood on their CT scan into perimesencephalic (PM) and non-PM (NPM) SAH. We performed the Outcome using Glasgow Coma Scale (GCS) and modified Rankin scale (favorable mRS 0–2 vs. unfavorable mRS 3–6). Data were analyzed using IBM® SPSS® Statistics V22.0.Results:The mean age at presentation was 48.5 ± 8.4 years with male predominance (71.4%). About 76.7% of the patients had headache and vomiting, most of the patients (75.3%) presented with GCS 15 at initial clinical presentation (61.03%) had NPM versus (38.96%) with PM characters in computed tomography scans. Fourteen (17.9%) patients developed hydrocephalus and 12 (15.3%) needed external ventricular drain placement, while none of the patients needed permanent shunt placement. However, all patients had a favorable clinical and functional outcome at discharge and at late follow-up (up to 3 months).Conclusions:NA-SAH does not affect the short- and long-term prognosis. In our results, the pattern of bleeding affects the initial presentation, clinical course, and complications. The clinical and functional outcomes in the majority of our patients were comparable in both groups with good prognosis. Hypertension, smoking, and elevated venous pressure, such as a history of deep venous thrombosis and asthma might be considered as a risk factor.

Prevalence and Clinical Presentation of Health Care Workers With Symptoms of Coronavirus Disease 2019 in 2 Dutch Hospitals During an Early Phase of the Pandemic

On February 27, 2020, the first patient with coronavirus disease 2019 (COVID-19) was reported in the Netherlands. During the following weeks, at 2 Dutch teaching hospitals, 9 health care workers (HCWs) received a diagnosis of COVID-19, 8 of whom had no history of travel to China or northern Italy, raising the question of whether undetected community circulation was occurring. To determine the prevalence and clinical presentation of COVID-19 among HCWs with self-reported fever or respiratory symptoms. This cross-sectional study was performed in 2 teaching hospitals in the southern part of the Netherlands in March 2020, during the early phase of the COVID-19 pandemic. Health care workers employed in the participating hospitals who experienced fever or respiratory symptoms were asked to voluntarily participate in a screening for infection with the severe acute respiratory syndrome coronavirus 2. Data analysis was performed in March 2020. The prevalence of severe acute respiratory syndrome coronavirus 2 infection was determined by semiquantitative real-time reverse transcriptase-polymerase chain reaction on oropharyngeal samples. Structured interviews were conducted to document symptoms for all HCWs with confirmed COVID-19. Of 9705 HCWs employed (1722 male [18%]), 1353 (14%) reported fever or respiratory symptoms and were tested. Of those, 86 HCWs (6%) were infected with severe acute respiratory syndrome coronavirus 2 (median age, 49 years [range, 22-66 years]; 15 [17%] male), representing 1% of all HCWs employed. Most HCWs experienced mild disease, and only 46 (53%) reported fever. Eighty HCWs (93%) met a case definition of fever and/or coughing and/or shortness of breath. Only 3 (3%) of the HCWs identified through the screening had a history of travel to China or northern Italy, and 3 (3%) reported having been exposed to an inpatient with a known diagnosis of COVID-19 before the onset of symptoms. Within 2 weeks after the first Dutch case was detected, a substantial proportion of HCWs with self-reported fever or respiratory symptoms were infected with severe acute respiratory syndrome coronavirus 2, likely as a result of acquisition of the virus in the community during the early phase of local spread. The high prevalence of mild clinical presentations, frequently not including fever, suggests that the currently recommended case definition for suspected COVID-19 should be used less stringently.

Phenotypical Characterization of Spleen Remodeling in Murine Experimental Visceral Leishmaniasis.

Background: Visceral leishmaniasis (VL) is caused by Leishmania infantum or L. donovani infection. One of the main problems related to this disease is the emergence of severe clinical forms with a lethality of 5–20%, even while under specific treatment. In humans and other species susceptible to fatal VL, such as dogs and hamsters, the disruption of splenic white pulp (WP) is accompanied by disease progression. Control of VL progression is seen in BALB/c mice, as evidenced by a mild clinical presentation and controlled parasite replication in the liver and spleen. In this study, we investigated the features involved in the morphological remodeling of splenic compartments associated with the control of VL progression to death.Methods: We evaluated cohorts of BALB/c mice after 30, 60, and 90 days of infection by L. infantum. Spleen morphology, cell population subsets and cytokine production were studied in the spleen using flow- and histo-cytometry.Results: Intraperitoneal infection with 108 promastigotes of L. infantum led to progressive increases in spleen size at 60 and 90 days after infection. Splenomegaly was the only clinical sign of disease observed. At 30 days after infection, hyperplasia in the WP and decreased numbers of plasmacytoid dendritic cells were observed. The WP hyperplasia subsided at 60 days post-infection. However, the splenomegaly remained in association with increased numbers of macrophages, B and T lymphocytes and plasma cells. An increased number of lymphoid tissue inducer (LTi) cells was observed; these were distributed around the periarteriolar lymphoid sheath in control mice and scattered throughout the red pulp in the Leishmania-infected mice. After 90 days of infection, increased IL-6 and IFN-γ production was seen in the spleen, as well as higher frequencies of follicular and plasmacytoid dendritic cells.Conclusion: The data presented herein emphasizes the potential role of spleen remodeling in the control of severe forms of VL and highlights features potentially involved in this process.

ISUOG Interim Guidance on 2019 novel coronavirus infection during pregnancy and puerperium: information for healthcare professionals.

ISUOG Interim Guidance on 2019 novel coronavirus infection during pregnancy and puerperium: information for healthcare professionals.

Unbalanced X;Autosome Translocations May Lead to Mild Phenotypes and Are Associated with Autoimmune Diseases

Unbalanced X;autosome translocations are a rare occurrence with a wide variability in clinical presentation in which the X chromosome unbalance is usually mitigated by a favorable X inactivation pattern. In most cases, this compensation mechanism is incomplete, and the patients show a syndromic clinical presentation. We report the case of a family with 4 women, of 3 different generations, carrying an unbalanced X;7 translocation with a derivative X;7 chromosome and showing a skewed X inactivation pattern with a preferential activation of the normal X. None of the carriers show intellectual disability, and all of them have a very mild clinical presentation mainly characterized by gynecological/hormonal issues and autoimmune disorders. We underline the necessity of family testing for a correct genetic consultation, especially in the field of prenatal diagnosis. We indeed discuss the fact that X;autosome translocations may lead to self-immunization, as skewed X chromosome inactivation has already been proved to be related to autoimmune disorders.

COVID-19: what is next for public health?

COVID-19: what is next for public health?

D-dimer: A Marker of Severity in COVID-19

Introduction: The ever-growing number of COVID-19 patients stresses upon the need to identify effective yet readily available predictors of disease severity to ensure better clinical outcomes. D-dimer is a fibrin specific degradation product derived by enzymatic action of plasmin on factor XIIIa cross-linked fibrin. It serves as an ideal marker for activation of coagulation and fibrinolytic pathways. Identification of coagulopathy as an important complication in COVID-19 patients has brought to focus D-dimer as a possible predictor of clinical severity in patients. Aim: In this study, we analysed the role of D-dimer levels in assessing the clinical severity of the COVID-19 patients. Materials and Methods: We enrolled 217 in-patients of Tirunelveli Medical College in this single centre observational study and classified them into asymptomatic, mild, moderate and severe according to “Clinical Management Protocol: COVID 19”, by the Ministry of Health and Family Welfare and Director General of Health Services. D-dimer was estimated in the separated plasma, using latex based assay using semi-automated coagulation analyser. Data were presented as percentages for categorical variables and median±Inter Quartile Range (IQR) for continuous variables. Chi-square test was used to compare the D-dimer values between symptomatic and asymptomatic groups. A value of p<0.05 was considered statistically significant. Results: Among the 217 cases, 88.9% were asymptomatic cases, 8.8% presented with mild clinical severity and 2.3% had moderate clinical presentation. In our study population, the Mean±SD and Median±IQR of D-dimer values (in ng/mL) were 223.4±230.6 and 157.0±187.7, respectively. The mean D-dimer value was found to increase as the category of our study group ascended from asymptomatic patients to mild and moderate clinical cases. It was noted that 91.1% of the cases who had D-dimer values <500 ng/mL were asymptomatic. Also, the odds of patients with high levels of D-dimer being clinically symptomatic was 5.5 times more than the odds of patients with D-dimer levels <500 ng/mL. Conclusion: Elevation of D-dimer levels associated with the severity of clinical course of patients infected with SARS CoV-2 when compared to patients with mild or asymptomatic clinical presentations.

Giardia duodenalis infection in dogs affected by primary chronic enteropathy.

Background:Canine primary chronic enteropathy (CE) includes a heterogeneous group of diseases characterized by chronic gastrointestinal signs.Aim:This study evaluated the occurrence of Giardia duodenalis infection in primary CE-affected dogs.Methods:Forty-seven CE-affected dogs of different age and sex were enrolled in the study. For each dog, frequency of defecation, fecal consistency, and eventual fecal abnormalities were evaluated. A clinical scoring index of CE severity (clinical chronic enteropathy activity index) was also assessed, and the type of enteropathy was retrospectively classified. For parasitological analysis, fresh fecal samples collected from each dog were examined by fresh and Lugol stained smears, flotation test, and a rapid immunoassay. Giardia duodenalis genotypes were identified by molecular analysis. Differences of clinical parameters between G. duodenalis positive and G. duodenalis negative dogs were statistically evaluated.Results:Among the CE canine patients, 16 out of 47 (34%) dogs were found positive for G. duodenalis and assemblages C and D were identified. No statistical differences emerged according to the types of CE between G. duodenalis-positive and G. duodenalis-negative dog groups. The clinical index of CE severity was indicative of significant less severe clinical forms in G. duodenalis-positive dogs (p = 0.037).Conclusion:Results here obtained shows how G. duodenalis may be present in primary CE-affected dogs and further investigations are needed to clarify the real significance of mild clinical presentation in G. duodenalis-positive dogs affected by CE.

Clinical and neuroradiological characteristics of ischemic stroke and subarachnoid hemorrhage in isolated posterior inferior cerebellar artery dissection: Literature review and report of 2 cases

Background/objectiveIsolated dissection of the posterior cerebellar artery (PICA) is very rare, with only few cases reported in the literature. Ischemic stroke or subarachnoid hemorrhage (SAH) may follow isolated PICA dissection depending on the dissection plane of the artery. The aim of this is study is to investigate similarities and variations in clinical, neuroradiological manifestations as well as the management and prognosis of ischemic stroke and SAH events in isolated PICA dissection. MethodWe report 2 cases of PICA dissection treated at our institution, one with ischemic stroke and other with SAH. Peer reviewed articles were used for insight on differences and similarities in presentation, management and prognosis between PICAD with ischemic stroke and SAH event. ResultsOccipital headache was noted to be the most common clinical presentation in both patients groups. Patients with SAH event presented with more severe symptoms compared to those with ischemic stroke. Susceptibility weighted imaging (SWI) was found to be better at detecting PICAD compared to conventional MRI/MRA. Digital Subtraction Angiography remains the gold standard diagnostic test for dissection. PICAD with ischemic stroke is likely under diagnosed. ConclusionPICAD with ischemic stroke is likely under-diagnosed due to the following reasons; 1) patients present with neurological deficits that are non-specific and mild, 2) DSA, which is a gold standard of diagnosing PICAD is not regularly performed in these patients, 3) lack of predisposing factors associated with PICAD in some patients. The mild and non-specific clinical presentation in young adults with PICAD with ischemia probably due to their ability to compensate better given low incidences of other comorbidities. Further investigation regarding the underlying etiology of isolated PICAD, association of proximal PICAD to ischemia and distal PICAD to SAH as well as use of SWI in detecting PICAD is recommended.

Wide phenotypic variability in RSPH9-associated primary ciliary dyskinesia: review of a case-series from Cyprus.

Primary ciliary dyskinesia (PCD) is an inherited ciliary motility disorder caused by mutations in at least 40 genes. RSPH9 gene mutations encoding aberrant radial spoke head proteins have been linked with PCD. The clinical spectrum extent of RSPH9 gene mutations remains to date largely unknown. We aimed to describe the diagnostic and clinical phenotype in a case-series of RSPH9-associated PCD. We performed whole exome sequencing in suspect patients from Cyprus who on repeated cilia biopsies demonstrated loss of the central pair apparatus on Transmission Electron Microscopy (TEM) and rotary beating patterns on High Speed Video Microscopy (HSVM), compatible to findings described previously in PCD patients bearing pathogenic RSPH9 mutations. In cases confirmed by genetic testing, we reviewed diagnostic, demographic and clinical data, as well as anthropometric and spirometric measurements. We diagnosed 7 individuals (5 females) homozygous for the novel RSPH9 splice site mutation c.670+2T>C in intron 4, who originated from two families. Despite bearing the same genetic variant, patients presented a highly variable age (median 47.9 years; range, 6.6 to 51.4 years) and with a diverse clinical picture, all reporting a history of chronic or recurrent wet cough (100%), and at varying frequencies neonatal respiratory distress (43%), chronic rhinosinusitis (71%), and wheezing (43%). Complications such as bronchiectasis (71%), history of pneumonia(s) (57%) and surgical interventions (43%) clustered in some patients displaying typical PCD, but not in others with milder phenotypes. BMI-z scores (median: 0.53; range, -0.69 to 1.52), FEV1-z scores (median: -0.37; range: -1.79 to 0.22) and FVC z-scores (median: -0.80; range: -2.01 to 0.36) were on average within the normal range, although slightly reduced. In conclusion, RSPH9-associated PCD disease demonstrates wide phenotypic variability. In some cases, mild clinical presentation is difficult to justify diagnostic work-up, highlighting the importance of wider adoption of genetic diagnostics. Larger studies are needed to assess variability of clinical spectrum associated to alterations of PCD genes.

K1 gene transformation activities in AIDS-related and classic type Kaposi\u2019s sarcoma: Correlation with clinical presentation

Kaposi’s sarcoma-associated herpesvirus (KSHV) causes both AIDS-related Kaposi’s sarcoma (KS) and classic KS, but their clinical presentations are different, and respective mechanisms remain to be elucidated. The KSHV K1 gene is reportedly involved in tumorigenesis through the immunoreceptor tyrosine-based activation motif (ITAM). Since we found the sequence variations in the K1 gene of KSHV isolated from AIDS-related KS and classic KS, we hypothesized that the transformation activity of the K1 gene contributes to the different clinical presentations. To evaluate our hypothesis, we compared the transformation activities of the K1 gene between AIDS-related KS and classic KS. We also analyzed ITAM activities and the downstream AKT and NF-κB. We found that the transformation activity of AIDS-related K1 was greater than that of classic K1, and that AIDS-related K1 induced higher ITAM activity than classic K1, causing more potent Akt and NF-κB activities. K1 downregulation by siRNA in AIDS-related K1 expressing cells induced a loss of transformation properties and decreased both Akt and NF-κB activities, suggesting a correlation between the transformation activity of K1 and ITAM signaling. Our study indicates that the increased transformation activity of AIDS-related K1 is associated with its clinical aggressiveness, whereas the weak transformation activity of classic type K1 is associated with a mild clinical presentation and spontaneous regression. The mechanism of spontaneous regression of classic KS may provide new therapeutic strategy to cancer.

Lactulose Induced Pneumatosis and Pneumoperitoneum: A Case Report

Pneumatosis intestinalis (PI) is the presence of gas within the bowel wall. The etiology of PI is variable and is associated with numerous conditions and medications. It can be benign or life-threatening. We present a rare case of PI and pneumoperitoneum secondary to chronic lactulose therapy. Our patient is a 75 year-old female with a history of NASH cirrhosis on lactulose for hepatic encephalopathy who presented with an incidental finding of right colonic wall PI on an outpatient CT scan performed for hepatocellular carcinoma screening. She reported minimal symptoms other than mild abdominal bloating. Her physical exam was remarkable only for mild right lower quadrant tenderness. She was afebrile with normal vital signs. Labs were unremarkable with a normal white blood cell count. A repeat CT on admission showed an interval worsening of the PI with a small focus of pneumoperitoneum. Colorectal surgery was consulted but given her mild clinical presentation, she was managed conservatively. Lactulose was discontinued and broad spectrum antibiotics were started. Of note, the patient had a colonoscopy one-year prior showing a small superficial ascending colonic ulcer with biopsy showing chronic ischemic changes. A follow-up CT angiography during her hospital course showed patent mesenteric vasculature with a significant improvement in PI and pneumoperitoneum only three days off lactulose therapy. She was eventually discharged on Rifaximin and a repeat CT scan two months later showed a complete resolution.2440_A Figure 1 No Caption available.2440_B Figure 2 No Caption available.The pathogenesis of PI is currently unknown. There may be a mechanical aspect causing gas to dissect into the bowel wall due to increased pressure. Gas-forming bacteria may also play a role by entering the submucosa through mucosal defects. Our patient had evidence of chronic ischemia to the right colon on prior colonoscopy. This, in combination with the mechanical stress from distension caused by lactulose may have allowed bacteria to enter the submucosa and precipitate PI. This phenomenon is not well understood and described only in case reports previously. Our case adds to the current literature and points to a subset of patients with chronic ischemia that may be particularly susceptible to this serious adverse event. Clinicians should be aware of this potentially life-threatening complication in patients with decompensated cirrhosis on chronic lactulose therapy.

Massive enlargement of all peripheral nerves

A 29 year old woman presented with three months of intermittent but increasing bifacial paraesthesia. On close questioning she reported five years of mild intermittent paraesthesiae in both hands and very mild proximal upper limb weakness. Examination revealed a small area of pinprick loss over the left cheek as the only abnormality. Nerve conduction study of both upper limbs demonstrated symmetric distal sensory and motor abnormalities strongly suggestive of demyelination (small or absent sensory potentials and markedly prolonged distal motor latencies). The remainder of extensive neurophysiologic assessment was normal. MRI brain and whole spine revealed massive symmetric enlargement of multiple cranial nerves, nerve roots, brachial and lumbosacral plexuses (Fig. 1A–F), without contrast enhancement. CSF showed albuminocytologic dissociation (protein 1.48 g/L) and extensive blood tests and whole body PET scan were normal. The most likely diagnosis isA.SarcoidosisB.Charcot Marie Tooth (CMT)C.Chronic Inflammatory Demyelinating Polyradiculopathy (CIDP)D.Leprosy CIDP was diagnosed based on these neurophysiologic, CSF and MRI findings and intravenous immunoglobulin (ivIg) was eventually commenced due to increasing symptoms. One year following presentation the patient was largely asymptomatic on maintenance monthly ivIg, with significant improvement in neurophysiologic parameters but no change in MRI features. The striking feature of this case was the extreme discordance between a mild clinical presentation of CIDP and the MRI findings of widespread and massive hypertrophy of multiple cranial nerves, nerve roots and plexuses. This point is highlighted by noting that the dramatic lumbar root and plexus MRI abnormalities were associated with absolutely no symptoms, signs or neurophysiological abnormalities. Massive peripheral nerve enlargement has a relatively limited differential diagnosis. Congenital causes, such as Charcot-Marie-Tooth or Neurofibromatosis; and acquired pathology, in particular leparomatous disease or an infiltrative process such as systemic amyloidosis, seemed unlikely given demyelinating neurophysiology that was clearly reversible with ivIg. Massive nerve root thickening on MRI has been reported in inflammatory conditions. The most common of these being CIDP, but to our knowledge this is the first report of massive cranial nerve enlargement in the condition [1Duggins A.J. McLeod J.G. Pollard J.D. et al.Spinal root and plexus hypertrophy in chronic inflammatory demyelinating polyneuropathy.Brain. 1999; 122: 1383-1390Crossref PubMed Scopus (193) Google Scholar, 2Adachi Y. Sato N. Okamoto T. et al.Brachial and lumbar plexuses in chronic inflammatory demyelinating polyradiculoneuropathy: MRI assessment including apparent diffusion coefficient.Neuroradiology. 2010; 53 ([published Online First: Epub Date]): 3-11https://doi.org/10.1007/s00234-010-0684-7Crossref PubMed Scopus (69) Google Scholar, 3Shibuya K. Sugiyama A. S-i Ito et al.Reconstruction magnetic resonance neurography in chronic inflammatory demyelinating polyneuropathy.Ann Neurol. 2015; 77 ([published Online First: Epub Date]): 333-337https://doi.org/10.1002/ana.24314Crossref PubMed Scopus (85) Google Scholar]. The initial report correlated massive root hypertrophy with a long and disabling disease course [[1]Duggins A.J. McLeod J.G. Pollard J.D. et al.Spinal root and plexus hypertrophy in chronic inflammatory demyelinating polyneuropathy.Brain. 1999; 122: 1383-1390Crossref PubMed Scopus (193) Google Scholar]. However subsequent case series have not found any definite correlation between nerve hypertrophy and disease severity or duration [2Adachi Y. Sato N. Okamoto T. et al.Brachial and lumbar plexuses in chronic inflammatory demyelinating polyradiculoneuropathy: MRI assessment including apparent diffusion coefficient.Neuroradiology. 2010; 53 ([published Online First: Epub Date]): 3-11https://doi.org/10.1007/s00234-010-0684-7Crossref PubMed Scopus (69) Google Scholar, 3Shibuya K. Sugiyama A. S-i Ito et al.Reconstruction magnetic resonance neurography in chronic inflammatory demyelinating polyneuropathy.Ann Neurol. 2015; 77 ([published Online First: Epub Date]): 333-337https://doi.org/10.1002/ana.24314Crossref PubMed Scopus (85) Google Scholar]. It is possible that MRI features differ between the various subtypes of CIDP and focal demyelination on neurophysiological testing of peripheral nerves has been associated with focal reversible contrast enhancement [3Shibuya K. Sugiyama A. S-i Ito et al.Reconstruction magnetic resonance neurography in chronic inflammatory demyelinating polyneuropathy.Ann Neurol. 2015; 77 ([published Online First: Epub Date]): 333-337https://doi.org/10.1002/ana.24314Crossref PubMed Scopus (85) Google Scholar, 4Kuwabara S. Nakajima M. Matsuda S. Hattori T. Magnetic resonance imaging at the demyelinative foci in chronic inflammatory demyelinating polyneuropathy.Neurology. 1997; 48 ([published Online First: Epub Date]): 874-877https://doi.org/10.1212/wnl.48.4.874Crossref PubMed Google Scholar]. However in routine practice MRI abnormalities simply provide supportive evidence of CIDP without specific management implications. The remarkable findings in our case suggest that massive hypertrophy can occur with very mild clinical disease. We propose that recurrent or chronic subclinical inflammation, demyelination and repair can lead to massive hypertrophy, almost as an oyster lays down layers of a pearl. Dr Fong was involved in the management and care of the patient and preparation and drafting of the manuscript. No disclosures relevant to this study are reported. Dr Masters was involved in the management and care of the patient and preparation and drafting of the manuscript and figures. No disclosures relevant to this study are reported. Dr Watson was involved in the management and care of the patient and preparation and drafting of the manuscript. No disclosures relevant to this study are reported.

An Atypical HNF4A Mutation Which Does Not Conform to the Classic Presentation of HNF4A-MODY

Objective To present the case of an atypical Hepatocyte Nuclear Factor 4 Alpha (HNF4A) mutation that is not consistent with the classically published presentation of HNF4A-Mature Onset Diabetes of the Young (MODY). Methods Clinical presentation and literature review. Results A 43-year-old nonobese man was referred to the endocrinology clinic for evaluation of elevated fasting blood glucose (FBG) measurements. Laboratory review revealed prediabetes and hypertriglyceridemia for the previous decade. Testing of autoantibodies for type 1 diabetes was negative. Genetic testing showed an autosomal dominant, heterozygous missense mutation (c.991C>T; p.Arg331Cys) in the HNF4A gene, which is correlated with HNF4A-MODY. Phenotypically, patients with an HNF4A-MODY tend to have early-onset diabetes, microvascular complications, low triglyceride levels, increased birth weight, fetal macrosomia, and less commonly neonatal hyperinsulinemic hypoglycemia. The patient did not demonstrate any of these features but instead presented with late-onset diabetes, an elevated triglyceride level, and a normal birth weight. Conclusion Our patient likely represents an atypical variant of HNF4A-MODY with a milder clinical presentation. Patients with atypical, less-severe presentations of HNF4A-MODY may be largely undiagnosed or misdiagnosed, but identification is important due to implications for treatment, pregnancy, and screening of family members.

Expanding the clinical spectrum of biallelic ZNF335 variants.

ZNF335 plays an essential role in neurogenesis and biallelic variants in ZNF335 have been identified as the cause of severe primary autosomal recessive microcephaly in 2 unrelated families. We describe, herein, 2 additional affected individuals with biallelic ZNF335 variants, 1 individual with a homozygous c.1399 T > C, p.(Cys467Arg) variant, and a second individual with compound heterozygous c.2171_2173delTCT, p.(Phe724del) and c.3998A > G, p.(Glu1333Gly) variants with the latter variant predicted to affect splicing. Whereas the first case presented with early death and a severe phenotype characterized by anterior agyria with prominent extra-axial spaces, absent basal ganglia, and hypoplasia of the brainstem and cerebellum, the second case had a milder clinical presentation with hypomyelination and otherwise preserved brain structures on MRI. Our findings expand the clinical spectrum of ZNF335-associated microcephaly.

Wilson's disease: A 2017 update

Wilson's disease (WD) is characterised by a deleterious accumulation of copper in the liver and brain. It is one of those rare genetic disorders that benefits from effective and lifelong treatments that have dramatically transformed the prognosis of the disease. In Europe, its clinical prevalence is estimated at between 1.2 and 2/100,000 but the genetic prevalence is higher, at around 1/7000. Incomplete penetrance of the gene or the presence of modifier genes may account for the difference between the calculated genetic prevalence and the number of patients diagnosed with WD. The clinical spectrum of WD is broader as expected with mild clinical presentations and late onset of the disease after the age of 40 in 6% of patients. WD is usually suspected when ceruloplasmin and serum copper levels are low and 24h urinary copper excretion is elevated. Recently, a major diagnostic advance was achieved with implementation of the direct assay of "free copper", or exchangeable copper (CuEXC). The relative exchangeable copper (REC) that corresponds to the ratio between CuEXC and total serum copper enables a diagnosis of WD with high sensitivity and specificity when REC>18.5%. Moreover, CuEXC values at diagnosis are a marker of extrahepatic involvement and its severity. A value of >2.08μmol/L is suggestive of corneal and brain involvement (Se=86%, Sp=94%), and the disease will be more clinically and radiologically severe as values rise. The use of FibroScan® is becoming more widespread to assess liver stiffness measurements in WD patients. 6.6kPa is considered to be a threshold value between mild and moderate fibrosis, whereas a value higher than 8.4 is indicative of severe fibrosis. More studies are now necessary to confirm the usefulness of Fibroscan® in managing chronic therapy for WD patients. Treatment of this disease is based on an initial active and prolonged chelating phase (with D-Penicillamine or Trientine) followed by maintenance with Trientine or zinc salt. The two major problems that may be encountered are neurological worsening during the initial phase and non-compliance with treatment during maintenance therapy. Liver transplantation is the recommended therapeutic option in WD with acute liver failure or end-stage liver cirrhosis; its indication should be considered when neurological status deteriorates rapidly despite effective chelation. Regular clinical, biological and liver ultrasound follow-up is essential to evaluate efficacy, tolerance and treatment compliance, but also to detect the onset of hepatocellular carcinoma on a cirrhotic liver. There are hopes in the near future with the introduction of a new chelator and inhibitor of copper absorption, tetrathiomolybdate (TTM) and the development of gene therapy.

Clostridium difficile infection is associated with graft loss in solid organ transplant recipients.

Clostridium difficile infection (CDI) is a leading cause of infectious diarrhea in solid organ transplant recipients (SOT). We aimed to assess incidence, risk factors, and outcome of CDI within the Swiss Transplant Cohort Study (STCS). We performed a case-control study of SOT recipients in the STCS diagnosed with CDI between May 2008 and August 2013. We matched 2 control subjects per case by age at transplantation, sex, and transplanted organ. A multivariable analysis was performed using conditional logistic regression to identify risk factors and evaluate outcome of CDI. Two thousand one hundred fifty-eight SOT recipients, comprising 87 cases of CDI and 174 matched controls were included. The overall CDI rate per 10000 patient days was 0.47 (95% confidence interval ([CI] 0.38-0.58), with the highest rate in lung (1.48, 95% CI 0.93-2.24). In multivariable analysis, proven infections (hazard ratio [HR] 2.82, 95% CI 1.29-6.19) and antibiotic treatments (HR 4.51, 95% CI 2.03-10.0) during the preceding 3months were independently associated with the development of CDI. Despite mild clinical presentations, recipients acquiring CDI posttransplantation had an increased risk of graft loss (HR 2.24, 95% CI 1.15-4.37; P=.02). These findings may help to improve the management of SOT recipients.

A CLINICAL STUDY OF COMPLICATED INGUINAL HERNIAS

Background and objectives Hernia is a common simple and easily treatable condition yet if ignored can lead to life- threatening complications. Lack of health awareness poverty and paucity of surgical facilities result in neglecting the condition for a long period of time. The patient ultimately approaches the emergency department with devastating complications. This study aims at illustrating the various modes of presentation management and post-operative outcome in complicated inguinal hernias.Methods The material for this study was collected from the patients of complicated inguinal hernia admitted in the Surgical Department of Basaveshwar Teaching and General Hospital attached to M.R. Medical College Kalaburagi from September 2015 to August 2017.Results In this study 50 cases of complicated inguinal hernia were studied. Among them 12 cases 24 presented within 24 hours of onset of symptoms while 38 cases 76 after 24 hours. Only 1case was female. 32 cases 64 were right sided and 16 cases 32 were left sided hernias. 2 cases 4 were bilateral hernias but had complication on only one side right side in both the cases. 44 of cases were irreducible 36 were obstructed and 20 were strangulated. 96 cases were indirect while only 4 were direct hernia. 82 cases were from rural and 18 cases th th from urban areas. Most common age of presentation was 4 and 5 decade. Most common mode of presentation was an irreducible swelling 100 followed by pain in 48 and vomiting in 46 cases. Small bowel was the most common content of the sac seen in 54 cases followed by omentum in 18 cases and small bowel with omentum in 16 cases. Most common surgery performed was herniorrhaphy in 74 cases followed by hernioplasty in 14 .There were 6 cases of strangulated hernia with non-viable bowel which underwent resection and anastomosis. There were 3deaths 6 all of them were late presented cases.Conclusion Patients who presented within 24 hours of onset of symptoms had mild clinical presentation shorter hospital stay lesser complications and no mortality. Whereas late presented cases gt24hrs had a more severe presentation prolonged hospital stay higher rate of complications and mortality. Most of the complicated cases were right sided and indirect inguinal hernias and in male patients. Patients from rural areas were found to have higher number of complicated cases than urban areas.