Gene-agnostic therapeutic approaches for inherited retinal degenerations.

Inherited retinal diseases (IRDs) are associated with mutations in over 250 genes and represent a major cause of irreversible blindness worldwide. While gene augmentation or gene editing therapies could address the underlying genetic mutations in a small subset of patients, their utility remains limited by the great genetic heterogeneity of IRDs and the costs of developing individualised therapies. Gene-agnostic therapeutic approaches target common pathogenic pathways that drive retinal degeneration or provide functional rescue of vision independent of the genetic cause, thus offering potential clinical benefits to all IRD patients. Here, we review the key gene-agnostic approaches, including retinal cell reprogramming and replacement, neurotrophic support, immune modulation and optogenetics. The relative benefits and limitations of these strategies and the timing of clinical interventions are discussed.

Varicella zoster meningitis: an atypical case of zoster reactivation in immunocompetent young adult.

Varicella virus is a neurotropic virus that can reactivate later in life to cause zoster or shingles. Typically, it affects elderly, immunocompromised population. We report an unusual case of an immunocompetent young adult presenting with occipital headache and zoster rash, without preherpetic and postherpetic neuralgia, who was diagnosed with varicella meningitis on Polymerase chain reaction (PCR). He was treated with intravenous acyclovir and later discharged on famciclovir. Diagnosis of varicella meningitis is difficult in the absence of typical features of zoster rash and requires high index of suspicion. Rapid diagnostic tests including varicella PCR and antithecal antibody testing can help in the confirmation of varicella zoster meningitis.

Clinical Features and Outcomes of Peripheral Vascular Disease Patients Receiving Red Blood Cell Transfusions.

Background Peripheral vascular disease (PVD) patients are commonly transfused with red blood cells (RBC) due to their inability to compensate for anemia and blood loss. Anemias, as well as allogeneic transfusions, have been demonstrated as independent risk factors for increased mortality and morbidity following cardiovascular procedures. The relationships between anemia, transfusion, and adverse outcomes in PVD patients remain unascertained and understudied. Methods A retrospective cohort study was conducted to determine mortality at 30-day, one-year, and three-year markers among 330 randomly selected PVD patients. The clinical features of patients receiving transfusions were examined, and the mortality rates were compared between patients who received an RBC transfusion and those who did not. Cox regression analysis was employed to identify independent variables predicting mortality. Results Transfusions were found to have increased mortality rates over non-transfused patients at 30 days (6.1% vs. 1.8%, p = 0.05), one year (21.8% vs 12.1%, p = 0.02), and three years (41.2% vs. 23.0%, p = 0.001). Using a multivariate regression model, it was determined that the transfusion itself was not a significant cause of this decrease in survival, while the propensity to transfuse was a predictor for both short (30 days, 36.73 [1.85-728.06], p = 0.04) and long-term mortality (one year (8.83 [2.62-29.77], p < 0.001; three years (7.07 [1.46-8.07], p <0.01). Anti-coagulation therapy using intravenous (IV) heparin and the chronic comorbidities of coronary artery disease and diabetes mellitus were also robust independent predictors of decreased survival. Conclusion This study was able to find an association between RBC transfusion and reduction in short-term (three months) and long-term (three years) survival. Those requiring IV heparin during the hospital stay were at an increased risk of requiring blood transfusion, and patients receiving IV heparin were also found to have a significant increase in mortality rates.

Changes in Nonosteoporotic Bone Density and Subsequent Fractures in Women.

OBJECTIVES: Osteopenia is considerably more common than osteoporosis and accounts for most of the fracture burden in women older than 50 years. It is uncertain when to initiate treatment in osteopenia. We sought to determine in women with osteopenia what effect transitioning to lower categories had on subsequent fracturing. METHODS: We surveyed 1150 women from office-based practices who had initial normal or osteopenic bone mineral densities (BMDs) and who were retested after 5.75 years. We classified categories related to baseline T scores as follows: normal (>-1.0), mild osteopenia (-1.0 to -1.49), moderate osteopenia (-1.5 to -1.99), and severe osteopenia (-2.0 to -2.49). We determined during a 9.6-year follow-up period the fracture occurrence in those who maintained their initial category status or transitioned into lower categories. RESULTS: Transitioning to lower categories was not significantly different among baseline osteopenic categories but significantly more than normal baseline BMDs. Total fractures, individuals fracturing, and major fractures were significantly more, with baseline T scores of ≤-1.5 (<0.001). Although only 10.2% transitioned to osteoporosis, 90.5% of these transitions occurred with baseline T scores ≤-1.5 and accounted for significantly more fractures than baseline T scores of >-1.5. CONCLUSIONS: Most subsequent fractures and transitions to osteoporosis occurred with baseline T scores ≤-1.5. Clinical risk factors need to be used to determine at what T score threshold treatment would be cost effective.

C-reactive protein and brain natriuretic peptide as predictors of adverse events after lower extremity endovascular revascularization.

BACKGROUND: High-sensitivity C-reactive protein (hsCRP) and brain natriuretic peptide (BNP) have been shown to be independent predictors of adverse cardiovascular outcomes and increased risk of secondary interventions or limb loss in patients with peripheral arterial disease (PAD). To assist clinicians in decision-making about treatment approaches and predicting postprocedure mortality and morbidity, we retrospectively examined patients with preprocedure hsCRP and BNP levels who underwent elective angioplasty or stent placement for lower extremity PAD. METHODS: The study period was from January 1, 2007, to December 31, 2012, and patients were included who had angioplasty or stenting for PAD. Minimal required follow-up for study inclusion was at least one postoperative ankle-brachial index, contrast angiography, or duplex imaging of the treated limb. Events of interest included major adverse limb events (MALE), defined as target vessel revascularization, amputation, or disease progression by 1 year, and major adverse cardiovascular events (MACE; stroke, myocardial infarction, or death) by 2 years. Elevated/abnormal values for our biomarkers of interest were established by the upper limits of our institution's clinical laboratory reference range (hsCRP, >0.80 mg/dL; BNP, >100 pg/mL). RESULTS: A total of 159 limbs in 118 patients were included in analysis (42% men; median age [range], 64 [42-87] years). All limbs were symptomatic (Rutherford classification: 1-6). Iliac artery revascularization without other adjunct lower extremity intervention was performed in 60% of the limbs. High hsCRP levels (>0.80 mg/dL) were present in 32 patients (27%) and high BNP values (>100 pg/mL) in 24 patients (20%). Kaplan-Meier analysis with log-rank comparison demonstrated that elevated hsCRP levels were associated with MALE but only in limbs receiving interventions distal to the iliac arteries (P = .005). High BNP levels did not affect MALE rates (P = .821). Conversely, both elevated BNP levels (hazard ratio, 5.6; 95% confidence interval [CI], 2.0-5.8; P = .001) and hsCRP levels (hazard ratio, 2.9; 95% CI, 1.1-7.6; P = .034) predicted MACE at 2 years in the presence of confounders in Cox proportional hazards multivariate analysis. Patients with high preintervention values of hsCRP and BNP were 10.6 times (95% CI, 2.6-42.9; P = .001) more likely to experience MACE than were patients with normal hsCRP and BNP values. CONCLUSIONS: After lower extremity endovascular interventions, elevated preprocedural hsCRP levels are associated with MALE (femoral-popliteal interventions), and elevated levels of hsCRP and BNP are associated with late cardiovascular events.

Marijuana induced hyperemesis: a case report.

Marijuana induced hyperemesis is a syndrome manifested by intractable nausea, vomiting and abdominal pain in someone who chronically uses marijuana with relief obtained from excessive bathing. This case report documents the exhaustive and costly work-up that has been performed in the case of one patient presenting to our facility with these complaints. It will also discuss marijuana induced hyperemesis syndrome in an effort to increase awareness of this under-diagnosed condition allowing for a more thorough history-taking and reduce unnecessary testing and radiologic examinations.

Mucormycosis of the middle ear: a case report with review of literature.

Mucor is a saprophytic organism and commonly invades the nose and paranasal sinuses of immunocompromised and diabetic patients involvement of the middle ear and mastoid in a nondiabetic patients is very rare and this may be the first case report clinical presentation of ear pain with reference to the mastoid and upper neck may be the early symptoms unlike the foul smelling ear discharge as seen in atticoantral disease. Radical debridement in the form of M.R.M with or without the use of amphotericin B may suffice in non-diabetic patients this case is reported to highlight the point that mucormycosis can also involve middle ear and mastoid in nondiabetic patients.

Cocaine abuse among patients: a study at the Charleston Area Medical Center.

UNLABELLED: Cocaine, an addictive central nervous system stimulant that can be inhaled, intravenously injected or smoked, is the second most commonly abused illicit drug in the United States. Its use is associated with numerous medical problems, as well as psychiatric disorders. This study 1) describes the clinical and demographic features of adult patients presenting with positive cocaine screens at Charleston Area Medical Center (CAMC) Emergency Room in 2006; 2) reports the percentage of those patients who volunteered their drug- use information; 3) reports the percentage of trauma patients who tested positive for cocaine use; 4) identifies other illicit drugs patients use with cocaine; and, how often these patients have psychiatric diagnoses. FINDINGS: In this study, the mean age of users was 35 years with a range of 18-57 years, many of whom had multiple visits to the hospital in the same year. Among the patients in this study, 24% had a history of depression and 15% had a history of bipolar disorder. Of the patients that tested positive for cocaine use, only 42% volunteered their drug-use history. The majority were found to have concurrent illicit drug use. The most common reasons for patients in this study to seek medical treatment were psychiatric and drug problems as opposed to medical reasons.

Elevated cardiac troponins in sepsis: what do they signify?

UNLABELLED: Serum troponins are sensitive markers used to diagnose acute coronary syndrome in association with signs and symptoms of chest pain and EKG changes. Cardiac troponins are elevated in 85% of patients with sepsis in the absence of acute coronary syndrome. Small studies have shown that elevated troponin levels identify patients with sepsis who are at increased risk of mortality. The purpose of this study was to (1) identify the outcome of cardiac troponin positive sepsis patients in our hospital, (2) determine whether the traditional cardiac risk factors predispose septic patients for positive troponin and (3) evaluate the cardiac interventions done for troponin positive patients. CONCLUSION: In our study, patients with elevated troponins had a higher mortality. Hypertension (HTN) and Coronary Artery Disease (CAD) increased the risk of mortality in troponin positive patients. Several interventions were performed including medications, echocardiogram, and cardiology consultation. Treatment medications did not improve mortality rates.

Surgical rescue and restoration of renal function in an anuric renal failure patient: a case report.

We present a case of anuric renal failure in a forty-nine year old woman secondary to bilateral renal artery occlusion that responded favorably to surgical revascularization. The patient presented with a three day history of diminished to absent urine output. The patient's BUN and creatinine were 52 mg/dL and 9.3 mg/dL, respectively. The patient remained anuric and required hemodialysis. Chronic atherosclerotic occlusion of both renal arteries with reconstitution of the renal arteries via collateral support was seen on angiography. Twenty-six days after presentation, the patient had aortorenal artery bypass using a saphenous vein graft. Postoperatively the patient had excellent diuresis with the creatinine improving to a nadir of 1.5 mg/dL. This case is a demonstration that the kidneys can remain viable with subacute renal artery occlusion in the presence of adequate collateral blood flow. Surgical or transcatheter renal revascularization should be considered in appropriate patients.

Factors causing patients to delay seeking treatment after suffering a stroke.

Many studies have looked at issues surrounding why people delay in accessing healthcare after they have experienced a stroke, but no published studies on this subject have been conducted in West Virginia. To identify the factors causing patients to delay treatment for a stroke, we conducted a concurrent chart review of 64 acute stroke and TIA patients presenting at Charleston Area Medical Center from April 1, 2003 to July 21, 2003. Results showed that the majority of patients arrived beyond the critical three-hour limit for tissue plasminogen activator (tPA) medication. The patients who reported speech problems and confusion as their initial symptoms, those who lived within 15 miles of the hospital, and those who used ambulance transport, were most likely to arrive at the hospital in less than two hours. On the other hand, the patients who were less likely to arrive within two hours were those who were alone at symptom onset, those who had weakness as a prominent symptom, as well as those were younger and had commercial insurance. We recommend educating the community about the symptoms of stroke and focusing on the fact that stroke is a medical emergency and calling 911 is necessary.