UNASSIGNED: Tenofovir is recommended as part of the first-line antiretroviral therapy (ART) to treat people living with HIV (PLWH) with HBV coinfection. However, the effects of tenofovir-containing ART on hepatocellular carcinoma (HCC) risk among PLWH with/without chronic hepatitis virus infections remain unclear.
UNASSIGNED: This study included 23,838 PLWH. All of them were males aged ≥20 years and followed prospectively during 2000-2017. Four major nationwide registries - the Human Immunodeficiency Virus surveillance database, Taiwan Cancer Registry, Death Certification System, and National Health Insurance Database - were applied to define ART and comorbidities and ascertain newly diagnosed HCC. Tenofovir-containing ART was identified through prescription records. Cox proportional hazards models were used to determine the association of tenofovir use with HCC incidence.
UNASSIGNED: HCC incidence was lower among ever users of tenofovir than among never users (24.2 and 85.7 per 100,000 person-years, respectively). Ever users had significantly reduced HCC risk (adjusted hazard ratio 0.20, 95% CI 0.13-0.31). The effect of tenofovir use on reduced risk for HCC consistently favored never users across many prespecified subgroups, including HBV or HCV coinfection (p <0.05). The findings were consistent in subgroups of PLWH diagnosed with HIV before tenofovir\'s approval and in those born before the nationwide roll-out of neonatal HBV vaccination.
UNASSIGNED: Our findings underscore the need for randomized controlled trials of tenofovir in combination with long-acting injectable ART regimens to assess its safety and efficacy in PLWH, particularly in those with HBV or HCV coinfection.
UNASSIGNED: Tenofovir\'s effect on the risk of hepatocellular carcinoma (HCC) among people living with HIV with hepatitis B or C coinfection remains under investigated. This nationwide prospective cohort study, comprising 23,838 men living with HIV, showed that tenofovir-containing antiretroviral therapy was associated with reduced risk of HCC (adjusted relative risk: 0.20, 95% CI 0.13-0.31), which was consistently observed across many prespecified subgroups. The effect of tenofovir use on HCC risk should be further investigated in PLWH, particularly following the development of long-acting injectable ART regimens.

Tuberculosis of the central nervous system is the second most common site after tuberculous meningitis. It represents 0.2% of intracranial expansive lesions in some Western countries compared to 10%-30% in developing countries. We report the case of an infant of 1 year and 2 months old who presented for 15 days with convulsions with asthenia, hypotonia, without fever. The clinical examination and laboratory workup were without abnormalities. His father had ongoing pulmonary tuberculosis, but the infant had no clinical or radiological signs of pulmonary tuberculosis. A brain MRI was showed multiple punctiform brain lesions, suggesting intracerebral tuberculomas in the first place, given the clinical and radiological appearance and the father\'s history of tuberculosis. The patient was put on anti-convulsant and antibacillary treatment. Through this case, we can see the clinical and radiological polymorphism of cerebral tuberculoma. The diagnosis of certainty remains anatomopathological. The prognosis is poor when it is detected late.

Although immune checkpoint inhibitors (ICIs) can be used for lung cancer treatment, the activated immune response may cause immune-related adverse effects (irAEs). We present here a case of cytomegalovirus (CMV) enterocolitis during steroid therapy for an irAE. A 70-year-old man diagnosed with small-cell lung carcinoma (limited disease) received radiotherapy plus two chemotherapy cycles of cisplatin and etoposide. The tumor exhibited complete response but recurred after 3 years. After treatment with two cycles of carboplatin, etoposide, and atezolizumab, an inhibitors of programmed cell death receptor-1, he was switched to atezolizumab every 3 weeks for maintenance therapy. Diarrhea occurred after nine atezolizumab doses. With a strong suspicion of ICI-induced colitis, we administered methylprednisolone 500 mg for 3 days, followed by oral prednisolone 40 mg/day. Total colonoscopy during the treatment revealed mucosal inflammation of the total colon, suggesting immune-related colitis. Biopsies from the ulceration revealed crypt abscess with highly infiltrative plasma cells and lymphocytes. Furthermore, immunohistochemical staining showed positivity for CMV. With no improvement in watery diarrhea, the prednisolone dose was increased to 80 mg/day on the 11th day, and ganciclovir was additionally administered twice daily on the 26th day. On the 28th day, the patient had abdominal pain, and abdominal computed tomography revealed free air, resulting in the diagnosis of colon perforation. He underwent subtotal colectomy followed by ileostomy as emergency surgery. A colon specimen revealed colitis with CMV infection. We describe colon perforation in a patient with CMV enterocolitis complicated by refractory immune-related colitis.

UNASSIGNED: High TB mortality is increasingly understood as an indicator of different problems in the health system and community. Limited awareness of TB in the community, restricted accessibility and/or quality of health services can hamper survival. Exploration and analysis of death among TB patients can lead to a clearer and specific understanding of why the deaths happened and where interventions are likely to make a difference in a specific context.
UNASSIGNED: The study aimed to assess why people die of active tuberculosis in the era of effective chemotherapy.
UNASSIGNED: The study was conducted from October to December 2020 in Arba Minch Health and Demographic Surveillance System (AM-HDSS) by applying phenomenological study design. A total of 27 family members of people who had died of TB, 9 health extension workers (HEW) and 8 health care professionals working in TB clinics were participated in open in-depth interview. A total of 130 individuals participated in 16 focus group discussion which composed of patient survived from TB, religious leader, health development army (HAD) and HEWs. Adequacy of information (saturation) was considered as an adequate sample size to create the intended qualitative product. All the interviews and FGD were tape recorded and recordings were transcribed immediately. ATLAS TI 9 software was used to analyse and process qualitative data. From data set codes were created then by identifying pattern among them themes were created. Then, generated themes were compared and some of them were split, combined, discarded and new ones created after returning to data set. Finally, themes were defined and a concise and easily understandable name was given for each theme.
UNASSIGNED: Luck of sufficient knowledge about TB was considered to be a reason for cause of death. Most of the time, TB patients underestimate and ignore when the symptoms first emerge and will not relate it with any diseases. The low level of community awareness about the cause, transmission, treatment and prevention highly contributed to increased transmission rate and death due to TB. The study identified misconceptions in the community; they prefer traditional medicine to the scientific way. First, they try different herbal medicine to get relief from their illness. At the end, if the disease is getting worse, they visit health facilities. Participants mentioned high transportation cost, poor health seeking behaviours, inadequate food consumption and lack of TB awareness as reasons for low treatment adherence. The health facilities were inaccessible for the community. Most of them indicated that health facilities were too far to reach. In some health institution, right amount and combination of medication were not delivery on time and Diagnostic facilities for TB were reported to be inadequate.
UNASSIGNED: Poor treatment adherence, lack of TB awareness, stigma, inadequate food consumption, poor health care seeking behaviour and inaccessibility of health facility were identified as major reasons for death. To prevent death of TB patients all sectors such as education, health, and agriculture should work to address health education, infrastructures, nutritional supplementation needs of TB patients, caregivers and the community as a whole.

People living with HIV are more exposed to the adverse health effects of the worldwide COVID-19 pandemic. The pandemic\'s health and social repercussions may promote drug abuse and inadequate HIV management among this demographic. The coronavirus pandemic of 2019 (COVID-19) has caused unprecedented disruption worldwide in people\'s lives and health care. When the COVID-19 epidemic was identified, people with HIV faced significant obstacles and hurdles to achieving optimal care results. The viral spike protein (S-Protein) and the cognate host cell receptor angiotensin-converting enzyme 2 (ACE2) are both realistic and appropriate intervention targets. Calanolides A, Holy Basil, Kuwanon-L, and Patentiflorin have anti-HIV effects. Our computational biology study investigated that these compounds all had interaction binding scores related to S protein of coronavirus of -9.0 kcal /mol, -7.1 kcal /mol, -9.1 kcal /mol, and -10.3 kcal/mol/mol, respectively. A combination of plant-derived anti-HIV compounds like protease inhibitors and nucleoside analogs, which are commonly used to treat HIV infection, might be explored in clinical trials for the treatment of COVID-19.

In visceral leishmaniasis (as in all leishmanial infections), microscopic diagnosis is made by observing the intracellular amastigote form, complete with a kinetoplast, in aspirate smears or biopsied tissue. In the 2 clinically-ill patients described here, intracellular inclusions were demonstrated in a bone marrow aspirate or a colon tissue biopsy. Kinetoplasts associated with the inclusions were not identified in the marrow aspirate smear (although the patient was treated for visceral leishmaniasis), but were identified retrospectively in the colonic tissue (although the patient was treated for histoplasmosis). Both cases illustrate the importance to clinical consultants of microscopically observing (or not) an associated kinetoplast when faced with a tissue aspirate or biopsy specimen showing intracellular inclusions.

UNASSIGNED: Pneumocystis pneumonia (PCP) is a life-threatening opportunistic infectious disease of immunocompromised patients. Its incidence has decreased worldwide in the past, but data concerning its recent epidemiology are lacking.
UNASSIGNED: We retrospectively analyzed all German inpatient cases from January 1, 2014 to December 31, 2019, to describe the recent epidemiology, incidence, clinical course, mortality and underlying diseases of PCP. Simultaneously, we conducted a retrospective multi-center study at two German university hospitals, and analyzed PCP cases treated there to gain deeper insights on the basis of primary patient data.
UNASSIGNED: The incidence of PCP significantly increased from 2·3 to 2·6 per 100,000 population from 2014 to 2019 (1,857 to 2,172 cases, +17·0%, p < 0·0001), as well as PCP-related deaths (516 to 615 cases, +19·2%, p = 0·011). The spectrum of underlying diseases changed: Risk groups with established chemoprophylaxis for PCP based on international guidelines (HIV, hematologic malignancies, and transplantation) showed a significant decrease in PCP cases and deaths. Others, especially those with solid malignancies, and autoimmune and pulmonary diseases showed a significant increase in case numbers and deaths. Data from the retrospective multi-center study added information regarding prophylaxis and diagnostics of PCP.
UNASSIGNED: The incidence of PCP has reversed its trend, showing a significant increase in mortality on population level. Patients who were not previously considered in prophylactic measures are increasingly affected by PCP. This development deserves further investigation, and additional comprehensive guidelines for the use of chemoprophylaxis in new risk groups are needed.
UNASSIGNED: Department of Nephrology and Hypertension, University Hospital Schleswig-Holstein, Kiel.

Pneumocystis pneumonia (PCP) typically occurs in immunocompromised individuals and rarely presents in immunocompetent individuals. A 55-year-old man was referred to our hospital with cough and anorexia that persisted for 2 months. Chest computed tomography revealed bilateral central consolidation. He was diagnosed with PCP via bronchoscopy. His symptoms and imaging findings improved with the administration of only trimethoprim and sulfamethoxazole. Although he had non-alcoholic fatty liver disease, there were no other complications that could potentially cause immunodeficiency. It should be noted that PCP in immunocompetent individuals can have a subacute disease course presenting with bilateral central consolidation.

Alzheimer\'s disease (AD), the most prominent form of dementia in the elderly, has no cure. Strategies focused on the reduction of amyloid beta or hyperphosphorylated Tau protein have largely failed in clinical trials. Novel therapeutic targets and strategies are urgently needed. Emerging data suggest that in response to environmental stress, mitochondria initiate an integrated stress response (ISR) shown to be beneficial for healthy aging and neuroprotection. Here, we review data that implicate mitochondrial electron transport complexes involved in oxidative phosphorylation as a hub for small molecule-targeted therapeutics that could induce beneficial mitochondrial ISR. Specifically, partial inhibition of mitochondrial complex I has been exploited as a novel strategy for multiple human conditions, including AD, with several small molecules being tested in clinical trials. We discuss current understanding of the molecular mechanisms involved in this counterintuitive approach. Since this strategy has also been shown to enhance health and life span, the development of safe and efficacious complex I inhibitors could promote healthy aging, delaying the onset of age-related neurodegenerative diseases.

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