A Simple Vitamin Deficiency With Life-Threatening Complications: A Case of B12 Deficiency and Hyperhomocysteinemia-Induced Thrombosis.

While macrocytic anemia is common in vitamin B12 deficiency, rarely, pancytopenia and hemolytic anemia can occur. Homocysteine levels are elevated in severe B12 deficiency, and this is linked to thrombus formation with potentially life-threatening complications. We present a patient with severe vitamin B12 deficiency complicated by hyperhomocysteinemia and obstructive shock from pulmonary embolism. A 56-year-old male with no medical history presented to the hospital with altered mentation. The patient's family stated he was experiencing bilateral paresthesias of his lower extremities, progressive depression, anxiety, and insomnia. Initial vitals were blood pressure of 76/36, heart rate of 70 beats per minute, respiratory rate of 14, and temperature of 36.3 degrees Celsius. He was intubated due to severe encephalopathy. Relevant labs indicated severe macrocytic anemia, thrombocytopenia, decreased B12 levels, elevated methylmalonic acid, and elevated homocysteine. Imaging demonstrated a right common femoral vein thrombosis and subsegmental pulmonary emboli. Peripheral blood smear revealed schistocytes, anisopoikilocytosis, and decreased platelet count. The patient required fluid resuscitation, antibiotics, and multiple blood products. Vitamin B12 was administered intramuscularly, which improved the anemia. Esophagogastroduodenoscopy (EGD) demonstrated gastritis. Gastric and duodenal biopsies were negative for Helicobacter pylori and celiac disease. He was negative for intrinsic factor (IF) antibodies but had elevated gastrin levels. An intravenous unfractionated heparin infusion was started when the platelet count was above 50000. The patient was extubated after seven days. Heparin was transitioned to apixaban and an inferior vena cava (IVC) filter was placed. Hyperhomocysteinemia is a known pro-thrombotic factor that can lead to the development of venous thromboembolism. B12 malabsorption can stem from inflammatory bowel disease, celiac disease, gastritis, pancreatic insufficiency, gastrectomy, gastric bypass surgery, or antibodies to IF. While this case showed gastritis and negative IF antibodies, gastrin levels were elevated, indicating a mixed picture. This highlights the challenge of definitively diagnosing pernicious anemia as the cause of vitamin B12 deficiency. Vitamin B12 deficiency may lead to critical illness in which thromboembolism develops secondary to hyperhomocysteinemia.

A diagnostic quandary: Rotavirus vaccine associated diarrhea.

The patient is an otherwise healthy two-month-old boy who received the recommended vaccinations for his age group, which included the rotavirus pentavalent vaccine (RV5; RotaTeq) at his two-month well child visit. Three days later, he developed prolonged non-bloody diarrhea and was found to have persistently positive rotavirus antigen in his stool. Subsequent workup revealed mild defects in his functional T-cell immunocompetence. Genetic testing was obtained through the Invitae panel and was negative for hereditary forms of primary immunodeficiencies. The rotavirus antigen was found to have cleared from his stool around four months after receiving the RV5. Unfortunately, the source of the rotavirus infection was unable to be determined. The caregivers had misconceptions about the vaccine and the child's immune system function which led to refusal of any further vaccinations. Healthcare providers should strive to develop honest and respectful relationships with parents to have thoughtful dialogues regarding vaccine safety and efficacy.

A novel case of homozygous PAX1 mutation associated with hypoparathyroidism.

The PAX1 gene plays an important role in the development of the parathyroid glands and the thymus. Mouse knockout models of PAX1, PAX3, and PAX9 have been found to have hypoplastic or absent parathyroid glands. To our knowledge, there are no reported cases of PAX1-associated hypoparathyroidism in humans. We present a case of hypoparathyroidism in a 23-month-old boy with a homozygous pathogenic variant in the PAX1 gene (PAX1 NM_006192.5 c.463_465del variant), predicted to cause an in-frame deletion of asparagine at position 155 (p.Asn155del) of the PAX1 protein. The hypoparathyroidism was unmasked after the patient developed significant hypocalcemia while receiving GoLYTELY (polyethylene glycol 3350, sodium sulfate anhydrous, sodium bicarbonate, sodium chloride, potassium chloride) for bowel cleanout. The patient had mild and asymptomatic hypocalcemia prior to hospitalization. The patient was noted to have inappropriately normal parathyroid hormone (PTH) level at the time of documented hypocalcemia thereby suggesting a diagnosis of hypoparathyroidism. Plain language summary: The first human case of hypoparathyroidism associated with a rare genetic disorder: a case report of PAX1 gene mutation The paired box (PAX) gene family is important for embryo development. One subfamily, PAX1, is necessary for development of the spinal column, thymus (important for the immune system development), and parathyroid (helps regulate the amount of calcium in the body). We present the case of a 23-month-old boy with known PAX1 gene mutation who came in with episodes of vomiting and poor growth. His presentation was thought to be most likely related to constipation. He was started on bowel cleanout medication and intravenous fluids. However, his calcium that had been mildly low subsequently dropped to very low levels. The level of parathyroid hormone (which helps regulate calcium levels) was inappropriately normal, meaning that his body was unable to make more, and was consistent with hypoparathyroidism. He was treated with calcium supplements and vitamin D and calcium levels normalized. He continues to be on calcium and vitamin D and calcium levels have remained stable. Doctors should keep this complication in mind when treating patients with PAX1 gene mutation.

Prevention of the Vertical Transmission of HIV; A Recap of the Journey so Far.

In 1989, one in four (25%) infants born to women living with HIV were infected; by the age of 2 years, there was 25% mortality among them due to HIV. These and other pieces of data prompted the development of interventions to offset vertical transmission, including the landmark Pediatric AIDS Clinical Trial Group Study (PACTG 076) in 1994. This study reported a 67.5% reduction in perinatal HIV transmission with prophylactic antenatal, intrapartum, and postnatal zidovudine. Numerous studies since then have provided compelling evidence to further optimize interventions, such that annual transmission rates of 0% are now reported by many health departments in the US and elimination has been validated in several countries around the world. Despite this success, the elimination of HIV's vertical transmission on the global scale remains a work in progress, limited by socioeconomic factors such as the prohibitive cost of antiretrovirals. Here, we review some of the key trials underpinning the development of guidelines in the US as well as globally, and discuss the evidence through a historic lens.

Identification Accuracy of Safety-Relevant Environmental Sounds in Adult Cochlear Implant Users.

OBJECTIVE: Examine cochlear implant (CI) users' ability to identify safety-relevant environmental sounds, imperative for safety, independence, and personal well-being. METHODS: Twenty-one experienced adult CI users completed an Environmental Sound Identification (ESI) test consisting of 42 common environmental sounds, 28 of which were relevant to personal safety, along with 14 control sounds. Prior to sound identification, participants were shown sound names and asked to rate the familiarity and, separately, relevance to safety of each corresponding sound on a 1-5 scale. RESULTS: Overall ESI accuracy was 57% correct for the safety-relevant sounds and 55% correct for control sounds. Participants rated safety-relevant sounds as more important to safety and more familiar than the non-safety sounds. ESI accuracy significantly correlated with familiarity ratings. CONCLUSION: The present findings suggest mediocre ESI accuracy in postlingual adult CI users for safety-relevant and other environmental sounds. Deficits in the identification of these sounds may put CI listeners at increased risk of accidents or injuries and may require a specific rehabilitation program to improve CI outcomes. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2388-2393, 2023.

Contribution of Verbal Learning & Memory and Spectro-Temporal Discrimination to Speech Recognition in Cochlear Implant Users.

OBJECTIVES: Existing cochlear implant (CI) outcomes research demonstrates a high degree of variability in device effectiveness among experienced CI users. Increasing evidence suggests that verbal learning and memory (VL&M) may have an influence on speech recognition with CIs. This study examined the relations in CI users between visual measures of VL&M and speech recognition in a series of models that also incorporated spectro-temporal discrimination. Predictions were that (1) speech recognition would be associated with VL&M abilities and (2) VL&M would contribute to speech recognition outcomes above and beyond spectro-temporal discrimination in multivariable models of speech recognition. METHODS: This cross-sectional study included 30 adult postlingually deaf experienced CI users who completed a nonauditory visual version of the California Verbal Learning Test-Second Edition (v-CVLT-II) to assess VL&M, and the Spectral-Temporally Modulated Ripple Test (SMRT), an auditory measure of spectro-temporal processing. Participants also completed a battery of word and sentence recognition tasks. RESULTS: CI users showed significant correlations between some v-CVLT-II measures (short-delay free- and cued-recall, retroactive interference, and "subjective" organizational recall strategies) and speech recognition measures. Performance on the SMRT was correlated with all speech recognition measures. Hierarchical multivariable linear regression analyses showed that SMRT performance accounted for a significant degree of speech recognition outcome variance. Moreover, for all speech recognition measures, VL&M scores contributed independently in addition to SMRT. CONCLUSION: Measures of spectro-temporal discrimination and VL&M were associated with speech recognition in CI users. After accounting for spectro-temporal discrimination, VL&M contributed independently to performance on measures of speech recognition for words and sentences produced by single and multiple talkers. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:661-669, 2023.

A Rare Case of Acne Medication-Induced Drug Reaction With Eosinophilia and Systemic Symptoms.

INTRODUCTION: Acne vulgaris is the most common skin condition in late adolescence and frequently requires systemic treatment with antibiotics or androgen receptor blockers in moderateto- severe cases. CASE PRESENTATION: We report the case of a 17-year-old adolescent female with new onset fever, headache, and pruritic rash 1 month after she started doxycycline and spironolactone for the treatment of acne vulgaris. Later, she developed eosinophilia and transaminitis. Infectious workup was negative. DISCUSSION: This presentation was consistent with a definite case of drug reaction with eosinophilia and systemic symptoms (DRESS). DRESS is a severe, systemic hypersensitivity drug reaction that typically occurs 2 to 8 weeks following exposure to the offending medication. CONCLUSIONS: Although doxycycline and spironolactone are uncommon triggers of DRESS, they are common medications used to treat acne, and clinicians should be aware of this potential complication when counseling patients, especially adolescents.

Endoscopic characterization of colorectal neoplasia with different published classifications: comparative study involving CONECCT classification.

Background and study aims The aim of this study was to validate the COlorectal NEoplasia Classification to Choose the Treatment (CONECCT) classification that groups all published criteria (including covert signs of carcinoma) in a single table. Patients and methods For this multicenter comparative study an expert endoscopist created an image library (n = 206 lesions; from hyperplastic to deep invasive cancers) with at least white light Imaging and chromoendoscopy images (virtual ± dye based). Lesions were resected/biopsied to assess histology. Participants characterized lesions using the Paris, Laterally Spreading Tumours, Kudo, Sano, NBI International Colorectal Endoscopic Classification (NICE), Workgroup serrAted polypS and Polyposis (WASP), and CONECCT classifications, and assessed the quality of images on a web-based platform. Krippendorff alpha and Cohen's Kappa were used to assess interobserver and intra-observer agreement, respectively. Answers were cross-referenced with histology. Results Eleven experts, 19 non-experts, and 10 gastroenterology fellows participated. The CONECCT classification had a higher interobserver agreement (Krippendorff alpha = 0.738) than for all the other classifications and increased with expertise and with quality of pictures. CONECCT classification had a higher intra-observer agreement than all other existing classifications except WASP (only describing Sessile Serrated Adenoma Polyp). Specificity of CONECCT IIA (89.2, 95 % CI [80.4;94.9]) to diagnose adenomas was higher than the NICE2 category (71.1, 95 % CI [60.1;80.5]). The sensitivity of Kudo Vi, Sano IIIa, NICE 2 and CONECCT IIC to detect adenocarcinoma were statistically different ( P  < 0.001): the highest sensitivities were for NICE 2 (84.2 %) and CONECCT IIC (78.9 %), and the lowest for Kudo Vi (31.6 %). Conclusions The CONECCT classification currently offers the best interobserver and intra-observer agreement, including between experts and non-experts. CONECCT IIA is the best classification for excluding presence of adenocarcinoma in a colorectal lesion and CONECCT IIC offers the better compromise for diagnosing superficial adenocarcinoma.

Safety-relevant environmental sound identification in cochlear implant candidates and users.

OBJECTIVES/HYPOTHESIS: To compare the identification of safety-relevant environmental sounds between experienced cochlear implant (CI) users and CI candidates. STUDY DESIGN: Cross-sectional. METHODS: A sample of 19 adult, postlingually deaf CI candidates (CI-Cs), 47 experienced CI users (CI-Es), and a control group of 37 age-matched normal-hearing adults were assessed using the Familiar Environmental Sounds Test-Identification (FEST-I). A subset of 11 sounds relevant for safety were selected for analysis in the current study. RESULTS: Analysis of safety-relevant sound identification accuracy revealed no significant difference in safety-relevant environmental sound identification skills between CI-E and CI-C participants, with average scores of 68.1% and 67.9%, respectively. Both performed substantially lower than age-matched normal hearing adults (95.1%). A significant moderate negative correlation (-0.4) was found between safety-relevant sound accuracy and chronological age only in one group, the CI-E group (r = -0.4, P < .005). CONCLUSIONS: These findings fail to demonstrate superior performance in safety-relevant environmental sound identification among CI-Es compared with CI-Cs. Although preliminary, these findings suggest that identification of safety-relevant sounds is a significant area of weakness for both CI-Es and CI-Cs, both of whom may benefit from rehabilitation. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:1547-1551, 2020.

Adenoma detection with blue-water infusion colonoscopy: a randomized trial.

Background and aims Colonoscopy is currently the reference method to detect colorectal neoplasia, yet some adenomas remain undetected. The water infusion technique and dying with indigo carmine has shown interesting results for reducing this miss rate. The aim of this study was to compare the adenoma detection rate (adenoma and adenocarcinoma; ADR) and the mean number of adenomas per patient (MAP) for blue-water infusion colonoscopy (BWIC) versus standard colonoscopy. Methods We performed a multicenter, randomized controlled trial in eight units, including patients with a validated indication for colonoscopy (symptoms, familial or personal history, fecal occult blood test positive). Consenting patients were randomized 1:1 to BWIC or standard colonoscopy. All colonoscopies were performed by experienced colonoscopists. All colonoscopy quality indicators were prospectively recorded. Results Among the 1065 patients included, colonoscopies were performed completely for 983 patients (514 men; mean age 59.1). The ADR was not significantly different between the groups; 40.4 % in the BWIC group versus 37.5 % in the standard colonoscopy group (odds ratio [OR] 1.13; 95 % confidence interval [CI] 0.87 - 1.48; P = 0.35). MAP was significantly greater in the BWIC group (0.79) than in the standard colonoscopy group (0.64; P = 0.005). For advanced adenomas, the results were 50 (10.2 %) and 36 (7.3 %), respectively (P = 0.10). The cecal intubation rate was not different but the time to cecal intubation was significantly longer in BWIC group (9.9 versus 6.2 minutes; P < 0.001). Conclusion Despite the higher MAP with BWIC, the routine use of BWIC does not translate to a higher ADR. Whether increased detection ultimately results in a lower rate of interval carcinoma is not yet known. CLINICAL TRIALS REGISTRATION: EudraCT 2012-A00548 - 35; NCT01937429.

Clostridium difficile: New Insights into the Evolution of the Pathogenicity Locus.

The major virulence factors of Clostridium difficile are toxins A and B. These toxins are encoded by tcdA and tcdB genes, which form a pathogenicity locus (PaLoc) together with three additional genes that have been implicated in regulation (tcdR and tcdC) and secretion (tcdE). To date, the PaLoc has always been found in the same location and is replaced in non-toxigenic strains by a highly conserved 75/115 bp non-coding region. Here, we show new types of C. difficile pathogenicity loci through the genome analysis of three atypical clinical strains and describe for the first time a variant strain producing only toxin A (A(+)B(-)). Importantly, we found that the PaLoc integration sites of these three strains are located in the genome far from the usual single known PaLoc integration site. These findings allowed us to propose a new model of PaLoc evolution in which two "Mono-Toxin PaLoc" sites are merged to generate a single "Bi-Toxin PaLoc".

Vocal classification of vocalizations of a pair of Asian small-clawed otters to determine stress.

Asian Small-Clawed Otters (Aonyx cinerea) are a small, protected but threatened species living in freshwater. They are gregarious and live in monogamous pairs for their lifetimes, communicating via scent and acoustic vocalizations. This study utilized a hidden Markov model (HMM) to classify stress versus non-stress calls from a sibling pair under professional care. Vocalizations were expertly annotated by keepers into seven contextual categories. Four of these-aggression, separation anxiety, pain, and prefeeding-were identified as stressful contexts, and three of them-feeding, training, and play-were identified as non-stressful contexts. The vocalizations were segmented, manually categorized into broad vocal type call types, and analyzed to determine signal to noise ratios. From this information, vocalizations from the most common contextual categories were used to implement HMM-based automatic classification experiments, which included individual identification, stress vs non-stress, and individual context classification. Results indicate that both individual identity and stress vs non-stress were distinguishable, with accuracies above 90%, but that individual contexts within the stress category were not easily separable.

Prognostic factors in patients with refractory ascites treated by transjugular intrahepatic porto-systemic shunt: From the liver to the kidney.

BACKGROUND: The aim of this retrospective study was to evaluate the prognostic value of different scores (including Child-Pugh and Model for End Stage Liver Diseases) in cirrhotic patients treated with transjugular intrahepatic porto-systemic shunt for refractory ascites. METHODS: Overall, 111 patients with transjugular intrahepatic porto-systemic shunt insertion between January 1998 and July 2012 were included. RESULTS: Survival rates (without transplantation) were 82.0% at 3 months, and 59.4% at 1 year. In addition to standard parameters, a new simple classification based on platelet count and glomerular filtration rate showed strong prognostic ability and could distinguish 3 groups of patients (Log-rank test, p<0.001): a "good-prognosis" group with platelet counts above 125×10(9)L(-1) and a glomerular filtration rate above 90 mL/min (1-year survival rate 92%), a "poor-prognosis" group with platelet counts below 125×10(9)L(-1) and a glomerular filtration rate below 90 mL/min (1-year survival rate 34.8%), and an "intermediate-prognosis" group (1-year survival rate 58.2%). Multivariate analysis showed a hazard ratio of 6.34 for the intermediate class and of 12.623 for the high class. CONCLUSIONS: A new and simple classification including platelet count and glomerular filtration rate is highly predictive of survival in patients with refractory ascites treated with transjugular intrahepatic porto-systemic shunt and could be used to select patients for this procedure.