Background and Objectives: Nintedanib is indicated for progressive pulmonary fibrosis (PPF) based on clinical trial results. The primary objectives of this study were to evaluate the effectiveness of nintedanib on forced vital capacity (FVC) and diffusing lung capacity for CO (DLCO) after one year of treatment, and to compare the annual rate of decline ("slope") for FVC, DLCO and 6 minute walking distance (6MWD) with the year prior to treatment. The secondary objectives were antifibrotic safety, tolerability, adverse events, immunosuppressant use, dyspnoea and survival. Materials and Methods: This study was a single-centre, retrospective, observational cohort study that included consecutive patients with PPF treated with nintedanib. Results: Fifty-five patients with non-IPF fibrotic ILD initiated nintedanib due to fibrosis progression. Most patients (63.4%) stabilised/improved FVC after 1 year of treatment, and 82.5% stabilised/improved DLCO. The "slope" of FVC and DLCO was reduced after 1 year of treatment compared to the year before initiation, although the difference was not statistically significant: FVC slope was +0.61% in the year after initiation vs. -2.3% in the year prior (mean change: 2.94%, 95%CI [-4.74, 10.62]); DLCO slope was -3.8% after treatment vs. -7% before initiation (mean change: 3.24%, 95%CI [-7.43, 13.92]). Dyspnoea improved in 23.2% of patients. A reduction in immunosuppressant use was observed after nintedanib initiation. Forty-one patients (74.5%) experienced at least one side effect: diarrhoea (60%), hepatotoxicity (23.6%), or asthenia (12.7%). Fifteen patients required permanent or temporary treatment discontinuation. Conclusions: In our real-world PPF cohort, most patients showed FVC and/or DLCO stabilisation or improvement after one year of nintedanib treatment. A non-significant reduction in the rate of FVC decline after one year of treatment was also observed, as was a reduction in symptom severity in our real-life PPF cohort.

In recent years, diseases caused by species of the genus Campylobacter have increased, due to improvements in identification methods, but also because, as part of global travel and trade, these species have spread to countries where no cases had previously been reported. The methodologies for their identification, whether classic through culture media and morphological characteristics, or using molecular biology or even proteomics techniques, play a fundamental role in establishing their diagnosis and providing timely treatment. Likewise, epidemiology will help guide this diagnosis when dealing with poorly defined diarrhoea, as well as the control and prevention of these infections. Similarly, expanding information on the relationship between these species and Guillain-Barré syndrome will lead to a better understanding and timely identification. We must not forget that both intrinsic and acquired antimicrobial resistance are key factors to consider for the successful treatment of infections caused by Campylobacter species.

Background and Clinical Significance:Giardia lamblia is a protozoan parasite that causes giardiasis, a gastrointestinal disease. The disease commonly manifests with abdominal pain, diarrhea, and emesis. Many giardia infections, however, are asymptomatic and can be easily spread to others. Bupropion, a norepinephrine and dopamine reuptake inhibitor, can have side effects of nausea and abdominal pain, which can mimic or overlap with symptoms of a Giardia lamblia infection. Case Presentation: We present a 39-year-old man who has sex with men (MSM) who presented with abdominal pain with nausea and vomiting. His symptoms began 3 months after returning from a trip to Peru and 1 month after starting bupropion. Bupropion was discontinued upon admission due to suspicion of medication-induced adverse effects. CT imaging revealed thickening of the transverse colon, suggestive of an infectious or inflammatory etiology. The patient's GI-PCR returned positive for Giardia lamblia, and the patient was treated with metronidazole. While the temporal relationship suggests an association, it remains unclear whether the clinical presentation was primarily driven by bupropion, the Giardia infection, or a synergistic effect of both. A norovirus result was indeterminate, and the patient improved after bupropion discontinuation but before metronidazole initiation, leaving open the possibility of a self-limited viral gastroenteritis. Conclusions: This case highlights a possible association between bupropion initiation and the temporal association between bupropion initiation and the detection of symptomatic giardiasis in an MSM patient. Clinicians may consider stool testing for Giardia before attributing gastrointestinal symptoms solely to medication effects. Giardia lamblia should be considered in the differential diagnosis of gastrointestinal symptoms for MSM patients, particularly when compatible exposure history, travel history, or enteric infection risk factors are present.

Patients with advanced or recurrent endometrial cancer have poor survival outcomes because effective treatment options remain limited. We investigated the efficacy and safety of cediranib plus weekly paclitaxel or olaparib versus weekly paclitaxel alone after prior platinum-based chemotherapy.

Chronic infections caused by Strongyloides stercoralis and Schistosoma spp. can present with longstanding gastrointestinal symptoms that mimic irritable bowel syndrome (IBS). In this case report, we describe a patient who was misdiagnosed with IBS for several decades before receiving a definitive diagnosis of chronic helminthiasis. Treatment with first-line antihelminthics resulted in complete and sustained resolution of symptoms. We review the life cycle, epidemiology, clinical presentations, diagnosis, and management of chronic helminthiases in the context of IBS. We further discuss the impact of misdiagnosis on both the patient and the healthcare system. Given the significant individual and economic burdens of IBS and the diagnostic uncertainty associated with low sensitivity of standard diagnostic tests for helminth infections, healthcare professionals should maintain a low threshold for testing and empiric treatment in patients with relevant travel and medical history.

Thymidine kinase 2 deficiency (TK2d) (MIM 609560) is an ultra-rare, autosomal recessive mitochondrial myopathy caused by TK2 variants, leading to mitochondrial DNA depletion and/or multiple deletions. People with thymidine kinase 2 deficiency experience progressive myopathy, bulbar weakness and respiratory insufficiency, often losing the ability to walk, eat and breathe independently. Doxecitine and doxribtimine represents the first approved treatment for patients with thymidine kinase 2 deficiency with age of symptom onset ≤12 years by the US Food and Drug Administration and the European Medicines Agency; previously, disease management was limited to supportive care. We investigated the efficacy and safety of pyrimidine nucleos(t)ide therapy in thymidine kinase 2 deficiency. Patients treated with pyrimidine nucleos(t)ides were pooled from retrospective (NCT03701568, NCT05017818) and prospective (NCT03845712) studies and company-supported Expanded Access Programs. Untreated patients were pooled from literature reviews and a retrospective chart review study (NCT05017818). Patient subgroups were stratified by age of thymidine kinase 2 deficiency symptom onset (≤12 years and >12 years). The primary outcome was survival in 50th-percentile matched pairs of treated and untreated patients. Other outcomes included status of developmental motor milestones, ventilatory and feeding tube support, and safety. In total, 218 patients were included (treated: 104; untreated: 114). Baseline demographics and characteristics were comparable between subgroups. Most patients had an age of symptom onset ≤12 years [treated: 82/104 (78.8%); untreated: 93/114 (81.6%)]. In the age-of-symptom-onset-≤12-years subgroup, restricted mean survival time (95% confidence interval) was 29.2 (28.2, 30.3) years over the 30 years after symptom onset for treated patients and 14.4 (11.1, 17.6) years for untreated patients. Loss of ≥1 acquired motor milestone was more frequent before treatment start than after. Substantially more patients regained ≥1 lost motor milestone after treatment start than before. Ventilatory and feeding support were used across all age-of-symptom-onset subgroups, but some patients reduced or discontinued support after starting treatment and fewer patients initiated support after treatment start than before. Most treatment-emergent adverse events (TEAEs) did not lead to discontinuation. The most frequent TEAE was diarrhoea [43/50 patients (86.0%)], which was generally mild or moderate and resolved with dose reduction. Serious TEAEs occurred in 28/50 patients (56.0%); few were considered to be drug related [4/50 (8.0%)]. In total, 3/67 patients (4.5%) experienced a fatal serious TEAE, which were not considered to be drug related. These findings indicate that pyrimidine nucleos(t)ide therapy improves survival and functional outcomes in people with thymidine kinase 2 deficiency, especially those with age of symptom onset ≤12 years, and has an acceptable safety profile.

We report primary analysis results from the Phase 3 PERSPECTIVE study comparing ibrutinib + rituximab versus placebo + rituximab in patients with previously untreated follicular lymphoma requiring treatment per Groupe d'Etude des Lymphomes Folliculaires criteria who were ineligible for chemoimmunotherapy due to age and/or comorbidities. The primary endpoint was investigator-assessed progression-free survival (PFS). Patients were randomly assigned 3:1 to receive ibrutinib (560 mg) or placebo once daily until progression, together with rituximab 375 mg/m2 weekly for 4 weeks, then every 8 weeks for 12 cycles. Overall, 445 patients were assigned to receive ibrutinib + rituximab (n = 334) or placebo + rituximab (n = 111). With a median follow-up of 53.7 months, PFS was significantly improved with ibrutinib + rituximab versus placebo + rituximab (hazard ratio, 0.713 [95% CI, 0.532-0.955]; P = 0.0231; median 42.0 vs. 32.8 months), as was overall response rate (81% vs. 68%; rate ratio, 1.190 [95% CI, 1.039-1.364]; P = 0.004). Complete response rates also favored ibrutinib + rituximab (31% vs. 26%). Overall survival (OS) was immature and not significantly different between arms (hazard ratio 1.121 [95% CI, 0.771-1.631]; P = 0.5485). Grade ≥3 adverse events occurred in 78% versus 57% of patients with ibrutinib + rituximab versus placebo + rituximab, most commonly neutropenia (16% vs. 7%), pneumonia (9% vs. 5%), hypertension (8% vs. 5%), COVID-19 (6% vs. 2%), COVID-19 pneumonia (6% vs. 3%), and diarrhea (6% vs. 2%). In patients with previously untreated follicular lymphoma, adding ibrutinib to rituximab significantly improved PFS and response rates but did not improve OS. This trial was registered at www.clinicaltrials.gov, NCT02947347.

Cholera has caused multiple pandemics and remains a significant global public health threat. After 18 years without autochthonous transmission in Brazil, a 60-year-old man with no travel history presented with abdominal discomfort and acute watery diarrhea. Laboratory testing detected Vibrio cholerae O1 Ogawa, prompting classification as a suspected cholera case. However, genomic analysis showed that the strain lacked the toxigenic virulence factor required to cause cholera, leading to its reclassification as a non-cholera case. This investigation highlights the importance of clinical suspicion, advanced laboratory diagnostics, and continuous epidemiological surveillance for accurate case identification and an appropriate public health response.

Non-typhoidal Salmonella infection usually causes self-limiting gastroenteritis, but a minority of cases are complicated by bacteraemia and extraintestinal focal infection. Vertebral discitis and osteomyelitis are rare complications, most often described in patients with diabetes, haemoglobinopathy, or immunosuppression. We describe a 67-year-old man with hypertension and previous percutaneous coronary intervention who attended the emergency department five times over six weeks with fever, rigors, diarrhoea, and worsening thoracic back pain after travel to Sri Lanka and the Maldives. Blood cultures grew Salmonella Java susceptible to ceftriaxone, ciprofloxacin, and co-trimoxazole. Initial CT of the chest, abdomen, and pelvis was unremarkable. CT angiography performed several weeks later showed mid-thoracic vertebral destruction and disc space change. MRI confirmed severe T6-T7 discitis and osteomyelitis with prevertebral soft tissue involvement of the adjacent oesophagus and azygous vein, together with periaortic enhancement from T5/T6 to T9. CT angiography found no aortitis. A repeat echocardiogram showed no evidence of infective endocarditis. Treatment required several antimicrobial adjustments, including prolonged intravenous ceftriaxone and later oral step-down to amoxicillin. Back pain improved substantially and serial radiographs showed no vertebral collapse. This case illustrates that Salmonella Java can seed the spine without classical immunocompromising risk factors and that the diagnosis is often delayed when persistent back pain is initially attributed to travel-associated gastroenteritis. Recurrent or unresolved symptoms after a confirmed Salmonella bacteraemia warrant early spinal MRI.