In the Eye of the Cytokine Storm: A Tale of SARS-CoV-2-Induced Acute Macular Neuroretinopathy.

Acute macular neuroretinopathy (AMN) commonly affects young to middle-aged females and is considered a relatively rare retinal disease, and the etiology is complex. Advances in multimodal imaging provide a better characterization of retinal disorders and have helped identify that one of the etiologies of AMN is microvascular in nature. This case is clinically relevant as it adds to the literature that the pathophysiology of AMN is vascular-driven. Our case is a 24-year-old Black female with no past medical history, the only medication she was taking was an oral contraceptive pill, who presented to the emergency room with a 24-hour history of left central field vision loss and endorsed a recent upper respiratory tract infection preceding the acute vision loss. It was subsequently found on admission that the patient tested positive for and had a SARS-CoV-2 infection. A retina specialist performed optical coherence tomography (OCT), which showed disruption in the outer segment junction, including the ellipsoid zone and outer plexiform. The use of multimodal imaging like OCT helped confirm AMN; therefore, prompt examination by ophthalmology is critical to confirm a correct diagnosis. This patient's vision improved and remained stable five months later. This case demonstrates that, like other viruses, SARS-CoV-2 has the potential to cause retinal disease complications such as AMN. These findings reinforce and add to the current literature that SARS-CoV-2 can cause multiple-organ system dysfunction at a vascular level through immune-mediated pathways.

A Life-Threatening Case of Torsemide-Induced Toxic Epidermal Necrolysis Associated With the Treatment of Anasarca.

Toxic Epidermal Necrolysis (TEN), along with Stevens-Johnson Syndrome (SJS), are rare, life-threatening delayed type IV hypersensitivity mucocutaneous skin disorders that can often be precipitated by medications. The most common culprits are sulfonamide antibiotics and various antiseizure medications. We report a case of a 41-year-old Black female that initially presented with SJS, which then rapidly progressed to TEN, confirmed by hematoxylin and eosin stain skin biopsies. Approximately 80% of her body surface area had necrosis and epidermal detachment lesions. It was concluded that TEN was caused by the use of torsemide for treatment of her underlying diffuse anasarca attributable to alcoholic cirrhosis. During her one-month hospital stay, a multi-disciplinary team consisting of dermatology, gynecology, rheumatology, nephrology, and infectious disease evaluated and treated the patient. Interventions included various supportive care measures as well as intravenous steroids, cyclosporine, plasma exchange, and intravenous immunoglobulin. Given that the mortality rate for TEN is over 30%, and this patient had end-stage cirrhosis, her prognosis was extremely poor. Even though her TEN eventually healed slowly, the patient experienced complications. This case demonstrates the importance of cautiously using sulfonamide medications in patients with known hypersensitivity to sulfa drugs.

A Case of Postural Orthostatic Tachycardia Syndrome Secondary to the Messenger RNA COVID-19 Vaccine.

Postural orthostatic tachycardia syndrome (POTS) is an impaction of the autonomic nervous system initiating orthostatic tachycardia. There are numerous triggers for POTS including viruses, vaccines, and an autoimmune basis. This case report is clinically relevant to better understand the pathophysiology behind the messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccine and the mechanism that triggers autonomic nervous system dysfunction. Furthermore, the overall goal of this case study is to report a unique side effect associated with the novel mRNA COVID-19 vaccine. A 42-year-old male, with no prior symptoms of sinus tachycardia and presyncope episodes, is diagnosed with POTS secondary to the first dose of the mRNA COVID-19 vaccine. Symptoms to this date include sinus tachycardia, dizziness, headaches, and fatigue that are often triggered after a large meal or standing for a longer duration. Numerous diagnostic tests and images failed to confirm any other diagnosis other than POTS. There was a sequential connection between the onset of symptoms approximately one week after taking the first dose of the mRNA COVID-19 vaccine. Currently, POTS in this patient is controlled by lifestyle modification. This case report has broader implications as it can help us understand how the mRNA vaccine works on the body relative to the immune system. Our theory is that the development of antibodies activates an autoimmune reaction that triggers POTS disease. The prevalence of the POTS dysautonomia post-vaccination will be clearer as more data and research are conducted on the side effects from the innovative mRNA vaccines created to combat severe acute respiratory syndrome coronavirus 2.

The effect of desvenlafaxine on cognitive functioning in employed outpatients with major depressive disorder: a substudy of a randomized, double-blind, placebo-controlled trial.

The objective of this substudy was to examine the effect of desvenlafaxine 50 mg/day compared with placebo on cognitive function in employed outpatients with major depressive disorder. A total of 11/55 (20%) study sites in a 12-week, randomized, double-blind, placebo-controlled trial administered cognitive assessments in memory, attention, and executive functioning domains using the cognitive drug research system. Changes from baseline were subjected to analysis of covariance with baseline levels as covariates, using last observation carried forward data. A significant improvement with desvenlafaxine 50 mg/day (n=52) compared with placebo (n=29) was observed on the quality of working memory composite measure (0.081 units (0.005, 0.156); P=0.0365) at last observation carried forward. Improvement from baseline on the speed of working memory composite was significant for desvenlafaxine (-226.6 msec (-316.7, -136.4); P<0.0001) and for placebo (-133.3 msec (-257.2, -9.4); P=0.0354); however, the treatment effect was not significant. No significant differences between groups were observed on composite measures for attention. Treatment of depression with desvenlafaxine 50 mg/day may improve aspects of cognitive functioning, including working memory.Clinical Trial Registry No.: Clinicaltrials.gov identifier: NCT00824291.

Glycemic control in familial vs. sporadic type 1 diabetes patients over 5 years.

BACKGROUND: Studies have shown that familial type 1 diabetes patients (FTID) have less severe metabolic derangement at presentation compared to sporadic patients (ST1D), but data on long-term metabolic control are lacking. OBJECTIVE/HYPOTHESIS: (1) FT1D will have less severe presentation and better HbA1c over 5 years compared to ST1D; (2) HbA1c in the offspring will correlate with parent HbA1c in parent-offspring group; and (3) HbA1c of the second affected sibling (SP2) will correlate with the first affected sibling (SP1) in sib-pairs. METHODS: Cohort of 33 parent-offspring and 19 sib-pairs; controls included 33 sporadic subjects matched by age, sex, ethnicity, puberty, and insulin regimen. Paired t-test and Pearson's correlation were used for statistical analysis. RESULTS: At diagnosis, mean age in FT1D vs. matched ST1D (7.7±4.9 vs. 7.6±4.5 years), mean HbA1c (9.6% vs. 10.7%), HCO3 (21 vs. 18 meq/L), glucose (428 vs. 463 mg/dL) and pH (7.35 vs. 7.36; p=ns) were not different. At 5 years, HbA1c (8.9% vs. 8.8%; p=0.81), clinic visits (12 vs. 12.5, p=0.68) and emergency room visits (0.48 vs. 0.24, p=0.10) were not different. In affected siblings, only HCO3 was different (SP1:18 vs. SP2: 24 meq/L; p<0.01). HbA1c for SP2 correlated positively with SP1 (r=0.67, p<0.01). Offspring HbA1c correlated positively with affected parents (9.3% vs. 8.6%, r=0.57, p=0.18) but was not significant. CONCLUSION: Metabolic control at diagnosis and at 5 years was similar in FT1D and ST1D. In sib-pairs, the second affected sibling had milder clinical presentation compared to the first affected sibling.

Growth hormone deficiency and central precocious puberty in Klinefelter syndrome: report of a case and review of KIGS database.

Growth hormone deficiency (GHD) and central precocious puberty (CPP) have each, individually, been described in patients with Klinefelter syndrome. However, the combination of GHD, CPP, and Klinefelter syndrome has never been reported. We described a Klinefelter syndrome patient who developed GHD at age 2 10/12 years and CPP at 8 6/12 years. Despite CPP, GnRH agonist therapy was not initiated because of his excellent predicted adult height. At 11 8/12 years, his height was 164.6 cm, close to his mid-parental target height of 165 cm. We report an additional nine patients with Klinefelter syndrome and GHD from the Pfizer International Growth Study (KIGS) database, none of whom had CPP. We conclude that the combination of GHD and CPP is very rare in Klinefelter syndrome and that CPP is unlikely to compromise final adult height.

An evaluation of sexual functioning in employed outpatients with major depressive disorder treated with desvenlafaxine 50 mg or placebo.

INTRODUCTION: The symptoms of major depressive disorder (MDD) include sexual dysfunction, but antidepressant pharmacotherapies are also associated with treatment-emergent sexual dysfunction. AIM: These secondary and post hoc analyses evaluated sexual functioning in employed adult outpatients with MDD treated with desvenlafaxine (administered as desvenlafaxine succinate) and placebo. METHOD: Patients were randomly assigned (2:1 ratio) to 12 weeks of double-blind treatment with desvenlafaxine 50 mg/day or placebo. MAIN OUTCOME MEASURES: The Arizona Sexual Experiences Scale (ASEX) was administered every 4 weeks. Analysis of covariance was used to compare differences in mean change from baseline ASEX scores between desvenlafaxine and placebo for women and men. RESULTS: There were 422 evaluable patients with baseline ASEX scores (desvenlafaxine, N = 281; placebo, N = 141). Among women (desvenlafaxine, N = 184; placebo, N = 92), baseline scores were 20.0 (5.2) and 20.5 (5.3) for desvenlafaxine and placebo, respectively; mean changes at week 12 were -1.93 (0.37) and -1.03 (0.54), respectively (mean difference: 0.90 [-0.38, 2.18]; P = 0.169). Among men (desvenlafaxine, N = 97; placebo, N = 49), baseline scores were 16.4 (4.9) and 15.9 (4.8) for desvenlafaxine and placebo, respectively; mean changes at week 12 were -1.13 (0.47) and -1.06 (0.70), respectively (mean difference: 0.07 [-1.59, 1.74]; P = 0.932). Significantly greater orgasmic dysfunction at week 12 was observed in the subgroup of men without baseline sexual dysfunction treated with desvenlafaxine relative to placebo. Conversely, women without baseline sexual dysfunction experienced poorer overall sexual functioning and orgasm satisfaction at week 12 with placebo relative to desvenlafaxine treatment. Subgroup analyses of treatment responders and nonresponders found no difference in the proportion of men or women that developed or had resolution of sexual dysfunction in the desvenlafaxine and placebo groups. CONCLUSION: With the exception of orgasmic dysfunction in men without preexisting sexual dysfunction, no significant negative effect on sexual functioning was observed over 12 weeks of treatment with desvenlafaxine.

Symptomatic and functional improvement in employed depressed patients: a double-blind clinical trial of desvenlafaxine versus placebo.

OBJECTIVE: This is the first study to assess the efficacy of desvenlafaxine (administered as desvenlafaxine succinate) for improving depressive symptoms and functioning exclusively in employed patients with major depressive disorder (MDD). METHODS: Gainfully employed (≥20 h/wk) male and female outpatients with MDD were randomly assigned (2:1 ratio) to 12 weeks of double-blind treatment with desvenlafaxine 50 mg/d or placebo. Analysis of covariance was used to compare differences in week 12 adjusted mean changes from baseline on the 17-item Hamilton Depression Rating Scale (HAM-D17) (primary outcome) and Sheehan Disability Scale (SDS) (key secondary outcome) in the intent-to-treat (ITT) population. A predefined, modified ITT population (ie, those in the ITT population with baseline HAM-D17 ≥20) was also analyzed. Tolerability was assessed by recording adverse events and change on the Arizona Sexual Experience Scale. RESULTS: Baseline HAM-D17 scores for desvenlafaxine (n = 285) and placebo (n = 142) were 22.0 and 21.8, whereas baseline SDS scores were 19.8 and 20.4. Adjusted mean differences between desvenlafaxine and placebo were 2.1 (95% confidence interval [CI], 0.78-3.46; P = 0.002) on the HAM-D17 and 1.3 (95% CI, -0.09 to 2.76; P = 0.067) on the SDS. For the modified ITT sample, desvenlafaxine (n = 208) and placebo (n = 102), baseline HAM-D17 scores were 23.8 and 23.9; the SDS baseline scores were 20.1 and 20.8. Mean differences were 2.6 (95% CI, 0.93-4.22; P = 0.002) on the HAM-D17 and 2.1 (95% CI, 0.36-3.76; P = 0.017) on the SDS. Adverse events and Arizona Sexual Experience Scale scores were comparable between groups. CONCLUSIONS: Desvenlafaxine 50 mg/d was efficacious for treating MDD in gainfully employed adults. Between-group differences on the SDS narrowly missed statistical significance in the ITT population alone, but the totality of data suggests functional improvements with active treatment.

Patient outcomes with education, drug therapy, and support: a study of venlafaxine ER-treated outpatients with major depressive disorder.

OBJECTIVE: Dialogues Time to Talk (Dialogues) is a care management program that provides additional follow-up care and patient education for outpatients with major depressive disorder (MDD) starting venlafaxine extended release (ER) therapy. This study examined the effect of the Dialogues program on patient treatment satisfaction. METHODS: In this 6-month, open-label study, primary care patients with MDD received usual care and were randomly assigned to venlafaxine ER (75 to 225 mg/d) either alone or in combination with the Dialogues program (venlafaxine ER + D). The primary outcome was patient treatment satisfaction on day 112, measured by the 10- point Satisfaction with Depression Care Scale (SDCS). Secondary efficacy outcomes included the 17-item Hamilton Rating Scale for Depression (HAM-D17) total score, response (≥50% decrease from baseline HAM-D17 score), and remission (HAM-D17 ≤ 7). RESULTS: The modified intent-to-treat population included 263 patients in the venlafaxine ER group and 257 in the venlafaxine ER+D group. The percentage of patients with an SDCS "very satisfied" score (≥8) at day 112 was not significantly different in the venlafaxine ER and venlafaxine ER+D groups (63% and 58%, respectively; P = 0.22). No significant differences were found on any secondary outcomes. CONCLUSION: Among primary care patients starting venlafaxine ER for MDD, participation in the Dialogues program did not have a statistically significant effect on patient treatment satisfaction.

Short-term efficacy and safety of desvenlafaxine in a randomized, placebo-controlled study of perimenopausal and postmenopausal women with major depressive disorder.

BACKGROUND: The risk for major depressive disorder (MDD) increases during the menopausal transition. Nonetheless, no large, placebo-controlled studies have prospectively assessed the efficacy of antidepressants in perimenopausal or postmenopausal women. This randomized, double-blind, placebo-controlled trial evaluated the short-term efficacy and safety of desvenlafaxine (administered as desvenlafaxine succinate) in perimenopausal and postmenopausal women with DSM-IV-defined MDD. METHOD: 387 depressed perimenopausal and postmenopausal women aged 40 to 70 years were randomly assigned to placebo or desvenlafaxine (100 or 200 mg/d at the discretion of the investigator) in an 8-week, flexible-dose trial conducted from September 2006 to June 2008. The primary efficacy variable was change from baseline in 17-item Hamilton Depression Rating Scale (HDRS(17)) total score, analyzed using a mixed-effects model for repeated-measures analysis. Safety data were collected throughout the trial. RESULTS: The reduction in adjusted HDRS17 total scores from baseline to week 8 (mean daily dose after titration, 162 to 176 mg/d) was significantly greater for desvenlafaxine (-12.64) compared with placebo (-8.33; P < .001). Statistical separation from placebo was observed at week 1 and was sustained through week 8. Both the perimenopausal and postmenopausal subgroups achieved significant reductions in HDRS(17) total scores with desvenlafaxine treatment (perimenopausal, P = .003; postmenopausal, P < .001). Response (58.6%) and remission (38.2%) rates were significantly higher for desvenlafaxine compared with placebo (31.6% [P < .001] and 22.4% [P = .008], respectively). In all, 19/256 (7.4%) desvenlafaxine-treated patients and 4/125 (3.2%) placebo-treated patients discontinued due to adverse events. Treatment-emergent adverse events were reported by 94/125 (75.2%) placebo-treated patients and 218/256 (85.2%) desvenlafaxine-treated patients. CONCLUSIONS: Short-term treatment with desvenlafaxine was effective and generally well tolerated in perimenopausal and postmenopausal women with MDD. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00369343.

Clinical utility of desvenlafaxine 50 mg/d for treating MDD: a review of two randomized placebo-controlled trials for the practicing physician.

BACKGROUND: Major depressive disorder (MDD) is a common, seriously impairing illness. Desvenlafaxine (administered as desvenlafaxine succinate) is the third serotonin-norepinephrine reuptake inhibitor (SNRI) approved in the United States for the treatment of MDD. Short-term clinical studies have demonstrated the efficacy and safety of 50 to 400 mg/d doses, with no evidence that doses greater than 50 mg/d confer additional benefit. OBJECTIVE: This paper summarizes published data on the efficacy, safety, and tolerability of the desvenlafaxine 50-mg/d recommended therapeutic dose for MDD and discusses clinical practice considerations. METHODS: A systematic review of MEDLINE, PsycINFO, and PubMed (all years through June 2009) was performed using the terms desvenlafaxine, DVS, and ODV. The criteria for inclusion in the review were a double-blind design, a placebo control or active comparator group, the 50-mg desvenlafaxine dose group, and enrollment of patients with a diagnosis of MDD. Posters were included if they reported on a study that was subsequently published in a manuscript. RESULTS: Overall results of two randomized, placebo-controlled, 8-week clinical trials demonstrated the efficacy of desvenlafaxine 50 mg/d for MDD. Statistically significant improvements compared with placebo were observed on the primary efficacy measure (17-item Hamilton Rating Scale for Depression [HAM-D(17)] total score; P < 0.05). Significant differences were observed on several secondary measures (Montgomery Asberg Depression Rating Scale scores in both trials [P < 0.05]; Clinical Global Impressions-Improvement scores [P < or = 0.01], Clinical Global Impressions-Severity scores [P < or = 0.01], HAM-D(17) response [P < or = 0.01] and remission [P < 0.05] in one trial each). Functional outcomes measures (Sheehan Disability Scale total and World Health Organization 5-Item Well-Being Index scores) were significant in both trials (P < 0.05). Safety results indicate desvenlafaxine treatment was safe and well tolerated; findings were consistent with the SNRI class. The generalizability of these findings is limited by the study protocols, which excluded patients with unstable comorbid medical conditions and also those with other Axis 1 and 2 psychiatric illnesses. Additionally, comparisons with other SNRIs are challenging given differences in study design. Desvenlafaxine can be initiated with the 50-mg/d therapeutic dose without titration and provides efficacy with rates of discontinuation due to treatment-emergent adverse events similar to placebo. In vitro data indicate desvenlafaxine has minimal inhibitory effects on cytochrome P450 (CYP) 2D6 and clinical studies show desvenlafaxine does not have a clinically relevant effect on CYP2D6 metabolism. In vitro data also indicate desvenlafaxine is not a substrate or inhibitor of the p-glycoprotein transporter. Plasma protein binding of desvenlafaxine is low (30%) and independent of drug concentration. Bioavailability is high at 80% after oral administration and is not affected by food. CONCLUSIONS: Desvenlafaxine 50 mg/d has demonstrated efficacy, safety, and tolerability for the treatment of MDD in two placebo-controlled trials. The metabolic profile of desvenlafaxine suggests a low risk of drug-drug interactions owing to minimal inhibitory effects on CYP2D6, lack of interaction with p-glycoprotein, and low protein binding.

A novel 1.4 Mb de novo microdeletion of chromosome 1q21.3 in a child with microcephaly, dysmorphic features and mental retardation.

A 2.5 years old girl presented with moderate mental retardation, microcephaly, arching eyebrows, low set ears, long eyelashes, persistent fetal pads and clinodactyly. About 1 Mb deletion in the chromosomal region 1q21.3 was identified using BAC array CGH analysis. The parental follow up FISH analysis was normal. Further study of the deletion using a 244K oligo-array of Agilent Technologies Inc., Santa Clara, CA, USA defined the deleted region to span about 1.4 Mb with approximate genomic location chr1:152,511,593-153,993,103 (NCBI genome build 36). This is a novel deletion, not reported to-date. Larger proximal 1q deletions that were previously reported typically included microcephaly, mental retardation and multiple congenital anomalies. The deleted region reported here includes at least 30 coding genes. Among them of interest is a three-gene cluster of the ephrin gene family (EFNA1, EFNA3 and EFNA4). This is a group of receptor protein-tyrosine kinase type genes with presumed, but not completely characterized function in nervous system development.

Early diffuse alopecia in a neonate with congenital syphilis.

Neonatal alopecia has been described in many circumstances but never as a part of the constellation of signs in congenital syphilis. Common clinical features of early congenital syphilis include hepatosplenomegaly, skeletal deformities, hematologic disturbances, and mucocutaneous features such as rhinitis and maculopapular rash. Syphilitic alopecia has previously been described only in conjunction with secondary syphilis. In this article, we describe the first occurrence of alopecia in a neonate with congenital syphilis.

The effect of quetiapine on psychosis and motor function in parkinsonian patients with and without dementia.

Recently, several small studies have indicated that quetiapine may be useful in the treatment of drug-induced psychosis in patients with PD. However, there have been questions related to atypical antipsychotic therapy and patient selection and how that may affect response and tolerability, especially worsening of the motor symptoms of PD. In particular, the presence or absence of dementia seems to be important. The aim of this study was to evaluate the effect of quetiapine on psychosis and motor symptoms in PD patients with and without dementia. A retrospective record review of patient responses to quetiapine was conducted. Response of psychosis was assessed through patient and caregiver interviews. Motor symptom change in relation to this therapy was assessed by patient and caregiver interviews and completion of the motor portion of the Unified Parkinson's Disease Rating Scale (UPDRSm). Analysis was performed by comparing psychosis and motor feature measures from before and after therapy for the group as a whole and for demented and nondemented subgroups, using nonparametric tests and Fisher's exact test. Forty-three consecutively treated PD patients were evaluated. The mean dose of quetiapine was 54 mg per day and the duration of therapy was 10 months. Eighty-one percent of patients demonstrated partial or complete amelioration of psychosis. Five patients (13%) experienced a worsening of PD motor symptoms, which was corroborated by changes seen in UPDRSm. When the group was examined as a whole, no significant change in UPDRSm score was noted. When demented (n = 20) and nondemented (n = 19) patients were compared, improvement in psychosis occurred in similar numbers of patients, but a significant difference in the numbers of patients who experienced a worsening of motor symptoms was seen (P < 0.02, Fisher's exact test). All five patients who complained of motor worsening were in the demented group. UPDRSm score after therapy tended to be worse in the demented group (P = 0.55, Mann-Whitney U test). There was no significant change in the levodopa dose. Approximately 80% of patients chose to continue therapy. We conclude that quetiapine is effective in improving psychosis in approximately 80% of PD patients both with and without dementia. Patients with dementia seem to have a higher propensity for worsening of motor symptoms.