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We then discuss models/drivers that have been proposed over the years to explain the evolutionary transition from mono- to holocentric chromosomes. We continue to review the description of holocentric chromosomes in diverse eukaryotic groups and then focus our discussion on a specific and recently characterized type of holocentromere organization in insects that functions independently of the otherwise essential centromeric marker protein CenH3, thus providing novel insights into holocentromere evolution in insects. Finally, we propose reasons to explain why the holocentric trait is not more frequent across eukaryotes despite putative selective advantages.
Cytomegalovirus (CMV) infection is common following thoracic organ transplantation and causes substantial morbidity and mortality. Letermovir is a novel antiviral agent used off-label in this population for CMV prevention. Our goal was to understand patterns of letermovir use and effectiveness when applied for CMV prophylaxis after thoracic transplantation.

We retrospectively evaluated letermovir use among thoracic transplant recipients at an academic transplant center who initiated letermovir from January 2018 to October2019 for CMV prophylaxis. We analyzed indication, timing, and duration of prophylaxis; tolerability; and occurrence of breakthrough CMV DNAemia and disease.

Forty-two episodes of letermovir prophylaxis occurred in 41 patients, including 37 lung and 4 heart transplant recipients. Primary prophylaxis (26/42, 61.9%) was utilized mainly due to myelosuppression (25/26, 96.2%) and was initiated a median of 315 days post-transplant (interquartile range [IQR] 125-1139 days). Sixteen episodes ofls of letermovir prophylaxis in this population are warranted.Previous studies in solid organ transplantation have shown a relationship between circulating eosinophil (EOS) counts and the presence of acute cellular rejection (ACR). However, the relationship between this potential biomarker and ACR in lung transplant (LTx) patients remains unclear.
To assess the association between EOS and the presence of acute cellular rejection in lung transplant recipients.

Retrospective study of 583 transbronchial biopsies (TBB) performed in 256 lung transplant patients between 2012 and 2018. We analyzed age, sex, underlying pathology, date of transplant, indications for TBB, presence and degree of ACR, and the simultaneous absolute and relative EOS.

ACR were observed in 170 of 583 TBB (29.2%). EOS in patients with ACR were higher than in patients without ACR (203.6 ± 248/mm
vs 103.1 ± 153/mm
; p < 0.001). High levels of both absolute and relative EOS were associated with the presence of ACR regardless of the underlying disease (odds ratio [OR] 1.003; 95% confidence interval [CI], 1.002-1.004; OR 1.226; 95% CI, 1.120-1.342) and time after transplant (OR 1.003; 95% CI, 1.002-1.004 and OR 1.239; 95% CI, 1.132-1.356). Moreover, both absolute and relative EOS were strongly associated with moderate and severe grades of ACR (OR 3.55; 95% CI, 3.00-4.10 and OR 3.56; 95% CI, 3.00-4.12).

EOS are elevated in ACR, especially in moderate or severe ACR. Increased vigilance for ACR is therefore advisable in lung transplant recipients with elevated EOS.
EOS are elevated in ACR, especially in moderate or severe ACR. Increased vigilance for ACR is therefore advisable in lung transplant recipients with elevated EOS.Blunt traumatic tracheobronchial injury is rare, but can be potentially life-threatening. It accounts for only 0.5%-2% of all trauma cases. Patients may present with non-specific signs and symptoms, requiring a high index of suspicion with accurate diagnosis and prompt treatment. A 26-year-old female was brought into the emergency department after sustaining a blunt trauma to the chest from a high impact motor vehicle accident. She presented with signs of respiratory distress and extensive subcutaneous emphysema from the chest up to the neck. Her airway was secured and chest drain was inserted for right sided pneumothorax. CT of the neck and thorax revealed a collapsed right middle lung lobe with a massive pneumothorax, raising the suspicion of a right middle lobe bronchus injury. Diagnosis was confirmed by bronchoscopy. In view of the difficulty in maintaining her ventilation and persistent pneumothorax with a massive air leak, immediate right thoracotomy via posterolateral approach was performed. The right middle lobar bronchus tear was repaired. There were no intra- or post-operative complications. She made an uneventful recovery. She was asymptomatic at her 1st month follow-up. A repeated chest X-ray showed expanded lungs. Details of the case including clinical presentation, imaging and management were discussed with an emphasis on the early uses of bronchoscopy in case of suspected blunt traumatic tracheobronchial injury. A review of the current literature of tracheobronchial injury management was presented.Periprosthetic joint infection (PJI) is the most difficult complication following total joint arthroplasty. Most of the etiological strains, accounting for over 98% of PJI, are bacterial species, with Staphylococcusaureus and Coagulase-negative staphylococci present in between 50% and 60% of all PJIs. Fungi, though rare, can also cause PJI in 1%-2% of cases and can be challenging to manage. The management of this uncommon but complex condition is challenging due to the absence of a consistent algorithm. Diagnosis of fungal PJI is difficult as isolation of the organisms by traditional culture may take a long time, and some of the culture-negative PJI can be caused by fungal organisms. In recent years, the introduction of next-generation sequencing has provided opportunity for isolation of the infective organisms in culture-negative PJI cases. The suggested treatment is based on consensus and includes operative and non-operative measures. Two-stage revision surgery is the most reliable surgical option for chronic PJI caused by fungi. Pharmacological therapy with antifungal agents is required for a long period of time with antibiotics and included to cover superinfections with bacterial species. The aim of this review article is to report the most up-to-date information on the diagnosis and treatment of fungal PJI with the intention of providing clear guidance to clinicians, researchers and surgeons.
Despite the advance in antibiotics and widespread chest tube drainage, acute empyema still shows a high mortality rate, accounting for 10-25%. We experienced a case of acute empyema caused by A. hydrophila, which is extremely uncommon, and reviewed all previously published articles.

A 76-year older man with a medical history of liver cirrhosis (LC) due to chronic hepatitis C and hepatic cell carcinoma was admitted to our institute. Elevated inflammatory reaction and effusions on chest CT were seen, and he was suspected of having acute empyema. Although an empiric antibiotic therapy of meropenem with chest tube drainage was performed as an initial treatment, he died within 8 hours of admission. Postmortem, both blood and left pleural fluid cultures yielded Aeromonas hydrophila. The final diagnosis was acute empyema caused by A. hydrophila. We reviewed previously reported empyema caused by Aeromonas species cases (4 A. hydrophila, and 1 A. veronii) in 4 previous reports written in English, including ours. Of 5, all were male, and the mean age was 52 years (range 27-76 years). All patients had LC due to alcohol or viral infections. As for antibiotics initially prescribed, third-generation cephalosporins were most frequently used in 3/5 (60%). Thoracentesis was performed in all patients (100%). As for prognosis, 2 (40%) survived, and 3 (60%) died.

Physicians should be aware of the possibility of acute empyema caused by A. hydrophila among patients with chronic hepatic disease.
Physicians should be aware of the possibility of acute empyema caused by A. hydrophila among patients with chronic hepatic disease.Unresectable anaplastic thyroid cancer (ATC) has a poor prognosis. Chemotherapy and radiotherapy have limited effects on it. Here, we present four cases who underwent immunotherapy for ATC. The patients were aged between 58 and 70 years. Two male patients with pulmonary metastases received pembrolizumab and lenvatinib. However, they died of septic shock and respiratory failure in 2.7 and 1 months, respectively, after the initiation of combination therapy. Another male patient with stage IVB disease was treated with spartalizumab. The tumor remained stable after surgical debulking but slightly progressed after 23 months. learn more He survived for 45.5 months after spartalizumab initiation. A female patient with BRAF-mutant ATC and lung metastases was treated with a combination of pembrolizumab and lenvatinib, which was complicated with grade 4 transaminitis. The patient subsequently received dabrafenib (a BRAF inhibitor) and trametinib (a MEK inhibitor) treatment, which was continued for 10.2 months with a best response of partial remission. She died 18 months after the initial diagnosis (11.4 months after treatment with dabrafenib and trametinib). In conclusion, the treatment responses of immunotherapy, either alone or in combination with other therapies, were highly variable in patients with ATC and should be carefully monitored along with the side effects.cCMP and cUMP have been identified in numerous biological systems and proposed to serve as second messengers. However, this proposal remained controversial because of the base-promiscuity of generators, effectors, phosphodiesterases, and bacterial toxins. With the identification of specific cytidylyl and uridylyl cyclases, cCMP and cUMP research enters a new era.Our objective was to systematically evaluate the efficacy and safety of intravenous (IV) iron therapy for treating anaemia in critically ill adults (>16 years) admitted to intensive care or high dependency units. We excluded quasi-RCTs and other not truly randomised trials. We searched 7 electronic databases (including CENTRAL, MEDLINE, and Embase) using a pre-defined search strategy from inception to June 14, 2021. One reviewer screened, extracted, and analysed data, with verification by a second reviewer of all decisions. We used Cochrane risk of bias (ROB) 1 and GRADE to assess the certainty of the evidence. We reported 3 comparisons across 1198 patients, in 8 RCTs (1) IV iron vs control (7 RCTs, 748 participants); our primary outcome (hemoglobin (Hb) concentration at 10 to 30 days) was reported in 7 of the 8 included trials. There was evidence of an effect (very-low certainty) in favour of IV iron over control in the main comparison only (6 RCTs, n = 528, mean difference (MD) 0.52g/dL [95%CI 0.23, 0.81], OB for lack of blinding, incomplete outcome data, baseline imbalance, and imprecision around the estimate (wide CIs and small sample size). In conclusion, the current evidence continues to support further investigation into the role for iron therapy in increasing Hb in critically ill patients. Recent, small, trials have begun to focus on patient-centred outcomes but a large, well conducted, and adequately powered trial is needed to inform clinical practice.
The objectives of this study were to include readmissions and physician costs in the estimates of total costs of severe maternal morbidity (SMM), to consider the effect of SMM on maternal length of stay (LOS), and to examine these for the more restricted definition of SMM that excludes transfusion-only cases.

California linked birth certificate-patient discharge data for 2009 through 2011 (n=1,262,862) with complete costs and LOS were used in a secondary data analysis. Cost-to-charge ratios were used to estimate costs from charges, adjusting for inflation. Physician payments were estimated from the mean payments for specific diagnosis-related groups. Generalized linear models estimated the association between SMM and costs and LOS.

Excluding readmissions and physician costs, SMM was associated with a 60% increase in hospital costs (marginal effect [ME] $3,550) and a 33% increase in LOS (ME 0.9days). These increased to 70% (ME $5,806) and 46% (ME 1.3days) when physician costs and readmissions were included.
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