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We sought to report the effectiveness of infliximab and adalimumab over the first 3 years of treatment and to define the factors that predict anti-TNF treatment failure and the strategies that prevent or mitigate loss of response.

Solid organ transplant (SOT) recipients are at increased risk of Clostridioides difficileinfection (CDI). For certain SOT recipients, an association between CDI and allograft loss, rejection, and mortality has been shown. Although limited by sample size, the authors observed that early CDI was not associated with those outcomes in their single-center investigation. Multicenter studies are merited to explore risk factors for CDI and associations with transplant-related outcomes in intestinal and multivisceral transplant recipients.

Anti-TNF drugs are effective treatments for the management of Crohn's disease but treatment failure is common. We aimed to identify clinical and pharmacokinetic factors that predict primary non-response at week 14 after starting treatment, non-remission at week 54, and adverse events leading to drug withdrawal.

The paradoxical response, a form of immune reconstitution inflammatory syndrome, merits immunosuppression in addition to antimycobacterial therapy in patients with nontuberculous mycobacterial (NTM) infections. Well-describe in Mycobacterium tuberculosis infections, the paradoxical response in NTM infections is less defi ned. The authors share an immunocompromised host with disseminated NTM and the paradoxical response that manifested with clinical worsening despite appropriate antimycobacterial therapy and improved with steroids.The paradoxical response, a form of immune reconstitution inflammatory syndrome, merits immunosuppression in addition to antimycobacterial therapy in patients with nontuberculous mycobacterial (NTM) infections. Well-described in Mycobacterium tuberculosisinfections, the paradoxical response in NTM infections is less defined. We share an immunocompromised host with disseminated NTM and the paradoxical response.

Purpose:We explored differences in changes in medical student empathy in the third year of medical school between volunteers at JeffHOPE, a multisite medical student–run free clinic of Sidney Kimmel Medical College (SKMC), and nonvolunteers. Method:Volunteerism and leadership experience at JeffHOPE were documented for medical students in the Class of 2015 (n = 272) across their medical educations. Students completed the Jefferson Scale of Empathy at the beginning of medical school and at the end of the third year. Students who reported participation in other Jefferson-affiliated clinics (n = 44) were excluded from this study. Complete data were available for 188 SKMC students. Results:Forty-five percent of students (n = 85) volunteered at JeffHOPE at least once during their medical educations. Fifteen percent of students (n = 48) were selected for leadership positions involving weekly clinic participation. Nonvolunteers demonstrated significant decline in empathy in medical school (P= 0.009), while those who volunteered at JeffHOPE at least once over the course of their medical educations did not show any significant decline (P= 0.07). Conclusions:These findings suggest that medical students may benefit from volunteering at student-run free clinics to care for underserved populations throughout medical school.

Progressive X-linked cone-rod dystrophy (COD1) is a retinal disease affecting primarily the cone photoreceptors. The COD1 locus originally was localized, by the study of three independent families, to a region between Xp11.3 and Xp21.1, encompassing the retinitis pigmentosa (RP) 3 locus. We have refined the COD1 locus to a limited region of Xp11.4, using two families reported elsewhere and a new extended family. Genotype analysis was performed by use of eight microsatellite markers (tel-M6CA, DXS1068, DXS1058, DXS993, DXS228, DXS1201, DXS1003, and DXS1055-cent), spanning a distance of 20 cM. Nine-point linkage analysis, by use of the VITESSE program for X-linked disorders, established a maximum LOD score (17.5) between markers DXS1058 and DXS993, spanning 4.0 cM. Two additional markers, DXS977 and DXS556, which map between DXS1058 and DXS993, were used to further narrow the critical region. The RP3 gene, RPGR, was excluded on the basis of two obligate recombinants, observed in two independent families. In a third family, linkage analysis did not exclude the RPGR locus. The entire coding region of the RPGR gene from two affected males from family 2 was sequenced and was found to be normal. Haplotype analysis of two family branches, containing three obligate recombinants, two affected and one unaffected, defined the COD1 locus as distal to DXS993 and proximal to DXS556, a distance of ∼1.0 Mb. This study excludes COD1 as an allelic variant of RP3 and establishes a novel locus that is sufficiently defined for positional cloning.

BackgroundSplenic granulomas (SG), are rare and a challenge in terms of diagnosis and treatment. There is no reported incidence for SG and they usually appear in young adults. Our patient presented with SG, as an extra-intestinal manifestation of VEO-IBD, which is described in children with ages between 2 to 6 years.Case ReportWe report the case of a 3 year old girl who developed multiple SG at the onset of Crohn’s Disease (CD), making her, to our knowledge, the youngest patient reported to have this extra-intestinal manifestation of IBD.Our patient presented after a few months of recurrent episodes of fever, vomiting, abdominal pain, weight loss and mouth ulcers. No infectious aetiology was found and she had normal immunological workup, CXR and Echocardiogram. Ultrasound (USS) of the abdomen showed hypoechoic splenic lesions. Intravenous (IV) Ceftriaxone and Metronidazole were started. Splenic biopsy was performed, as despite an 8 week course of IV and oral antibiotics there was no resolution of her symptoms and USS findings. Splenic biopsy showed non-caseating granulomas. She had further tests: tuberculosis screening and faecal calprotectin (FC).Her FC was raised, hence she had upper and lower gastrointestinal tract endoscopies and video capsule endoscopy (VCE), which showed multiple ulcers throughout the small bowel, confirming a diagnosis of VEO-CD. She was started on Modulen and Azathioprine and her gut symptoms and SG resolved on the USS. After the initial improvement her gut symptoms returned and Infliximab was then added to her management.ResultsFour months after commencing Infliximab, our patient experienced abdominal pain, mouth ulcers and anorexia. Her repeat FC was elevated. Repeat endoscopies and MRI reconfirmed the diagnosis of active CD in the stomach, small bowel and colon. Both Azathioprine and Infliximab doses were increased with improvement in symptoms. Her splenic lesions resolved after initial dietary treatment. She is being monitored with regular abdominal ultrasound.ConclusionOur case is unique due to the age of the patient and the atypical features of VEO-IBD, the splenic manifestation preceding the gut disease. Her symptoms were comparable to those of patients with SG. Similar to our case, patients with VEO-IBD usually do not respond to first line treatment, therefore biologics are often used early on in this disorder. Further studies on VEO-IBD need to be undertaken to help us manage this unusual disease entity.